We present the unusual case of an immunosuppressed patient suffering from unexpected superinfected invasive aspergillosis with cerebral, pulmonal, and adrenal manifestations, mimicking a metastasized bronchial carcinoma.
Central nervous system (CNS) infections with aspergillus are rare and potentially fatal [
3,
4]. Microscopically, aspergillus species are characterized by dichotomous branching, septated hyphae [
1]. The primary acquisition route for acquiring aspergillus is the inhalation of fungal conidia, which are spores that subsequently reach the upper and lower respiratory tract. Therefore, the paranasal sinus and the lungs are the most common sites of primary aspergillus infection [
2]. However, 40% of patients develop extrapulmonary manifestation, with 10–20% demonstrating CNS involvement [
4]. The most important risk factors for brain infections are neutropenia and corticosteroid use. In addition, immunocompromised, organ transplant recipients, oncological, hematological, and acquired immune deficiency syndrome patients are at higher risk [
2,
4]. Neuroaspergillosis may develop due to extension from the paranasal sinuses and mastoid air cells or by direct penetration after cranial trauma and operations. However, hematogenous dissemination from invasive lung infection is more common in immunocompromised patients [
3,
5]. In this population, a mortality rate of > 90% has been reported [
4]. Clinical symptoms of an aspergillus infection are unspecific and depend on the location of the fungus. Patients may present with fever, headache, lethargy, altered mental status, seizures, dizziness, gait disorders or other focal neurological deficits [
6]. Classically, CSF studies show mononuclear pleocytosis, elevated proteins and normal to reduced glucose values [
5]. Microbiological diagnosis of CSF is limited to culture because other methods such as PCR have only been validated in serum and bronchoalveolar lavage specimens [
3]. Galactomannan, a polysaccharide antigen located in the cell wall of aspergillus can be detected by enzyme-linked immunosorbent assay [
7]. However, we did not perform galactomannan testing, since the diagnosis was already established by histology. Brain imaging is often helpful in establishing the diagnosis, although CT and MR findings are non-specific. Ring-enhancing lesions are not uncommon, but contrast enhancement may be completely absent. Dural enhancement may occur with generalized meningoencephalitis. On unenhanced T1-weighted MRI, aspergillus foci usually appear hypo- to isointense and hypointense on T2-weighted images. Areas of T1-high signal intensity may also be seen in case of hemorrhage. Hemorrhage occurs in approximately 25% of lesions [
8,
9]. Furthermore, aspergillus hyphae may invade the walls of small and large blood vessels which results in initial thrombosis, leading to infarction or development of mycotic aneurysms. With regard to therapy, there are only few reports of patients surviving neuroaspergillosis with antifungal medications alone [
2]. Importantly, surgical resection must always be complemented with antimycotic medication.
The presented patient was receiving immunosuppressive medications, including corticosteroids (after kidney transplantation). Thus, she harbored an increased risk for developing neuroaspergillosis. Her clinical findings were limited to a single tonic-clonic seizure and imaging features were nonspecific. The presented case illustrates that despite the unspecific clinical findings, it is important to include fungal infections in the differential diagnosis, especially in the setting of immunosuppression from whatever cause. Interestingly, the situation was complicated by a concomitant bacterial infection. The intraoperative findings were atypical in this regard and only microbiological cultures revealed streptococcus infection. Although superinfections are recognized in patients who are immunocompromised undergoing surgery, the detection of a bacterial infection may further confound establishing the definitive diagnosis, as in the presented case. Panfungal PCR from CSF (samples taken before starting the antibiotics) were negative. Although PCR from CSF is considered an experimental diagnostic methodology, it may prove helpful in certain cases. In the present case, however, the definitive diagnosis of aspergillus infection could only be established after histological examination of the resected mass, which is considered the gold standard.
In conclusion, invasive aspergillosis of the CNS is a rare but increasingly prevalent disease, especially in immunocompromised patients. The infection may be isolated or combined with other infectious diseases. Accordingly, a high index of suspicion should be maintained in the setting of immunosuppression. Clinical and radiological findings are often unspecific and even misleading. Definite confirmation usually relies on tissue diagnosis with histochemical stains. Surgical resection is crucial for establishing the diagnosis and guiding therapy with targeted antifungal medications.