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.