Teaching Case

A 34-year old HIV positive woman with dizziness, ptosis and blurred vision of the left eye, had multiple brainlesions on imaging.

A 34-year-old HIV positive woman was admitted to the hospital with complaints of dizziness, ptosis and blurred vision of the left eye. Two days prior to admission, a CT scan of the brain had been made in another hospital; this examination revealed an enhancing lesion in the mesencephalon. Clinical examination upon admission revealed a cachectic patient, oriented to time and place. She had ptosis and mydriasis of the left eye. Temperature was normal. Auscultation of heart and lungs was unremarkable. Clinical neurological examination revealed normal strength and reflexes of the upper extremities, tremor of the left hand, normal strength of the lower extremities but no reflexes. The patient tended to fall to the right. MR imaging of the brain was performed, with the following sequences: precontrast sagittal T1-weighted (Fig. 1) and axial T2-weighted images (Fig. 2), postcontrast axial (Fig. 3) and coronal T1-weighted images (Fig. 4). The Gd-enhanced scans revealed multiple ring-enhancing and nodular lesions in the brain. The most prominent lesion was located in the left thalamic-mesencephalic region. On T2-weighted images, this lesion was hyperintense, with a hypointense peripheral rim. On the basis of the imaging findings, and in the clinical setting of an immunocompromised patient, an opportunistic brain infection was suspected. However, blood tests for Treponema Pallidum, Leishmania, Toxoplasmosis, CMV, and Herpes simplex were all negative. Cerebrospinal fluid was negative. The patient’s clinical condition deteriorated and she developed breathing difficulties. She was transferred to the intensive care unit. A chest X-ray showed two cavitated lesions with peripheral infiltrate, one in each lung (Fig 5). Because the etiology of the infection was still not clear, bronchoscopy was performed, and a stereotactic punction biopsy of the brainstem lesion was scheduled. Both investigations showed the presence of hyphal elements with septae and dichotomous branching, indicative of aspergillosis. The patient expired after a few days.

Aspergilloma in the brain in HIV positive patients is relatively infrequent. Exact statistical data are not available because the diagnosis is difficult and often unrecognised until autopsy. Autopsy studies of 1994 suggest a prevalence of 4 % [1], in 1998 a case control study suggested a prevalence of 7 % [2]. The increasing prevalence of cerebral aspergillosis is probably associated with the increased survival of immunocompromised patients. The brain is, after the lungs, the second most common organ to be infected by aspergillosis. Major risk factors for aspergillosis are neutropenia and corticosteroid use. In one-fourth of the HIV positive patients with aspergillosis, the brain was the only infected site, in other cases there was additional aspergillus infection, with the lungs and sinuses as most common sites [3]. Patients present with focal clinical neurologic symptoms, seizures, paresthesia, headache and altered mental status. Three patterns of neuroimaging of cerebral aspergillosis are identified [4]. The first and most common pattern consists of ring-enhancing lesions. MR imaging shows the lesions to be hyperintense on T2-weighted scans; the peripheral rim, however, is hypointense and irregular. After intravenous Gd-injection, the pattern of ring-enhancing lesions is indicative of abscess formation. The second pattern is that of multiple hypodense lesions on CT scanning with hyperintensity on T2-weighted MR images, this is consistent with embolic infarction. The third pattern is enhancing abnormalities of the sinuses and orbit, with secondary dural enhancement. Differential diagnosis includes: cryptococcosis, coccidiomycosis, toxoplasmosis, tuberculoma, lymfoma, pyogenic abscesses, metastatic disease and subacute hematomas. In aspergillosis, analysis of cerebrospinal fluid is not diagnostic, but can be used to evaluate other possible diagnosis such as cryptococcosis. Definitive diagnosis is made by biopsy. The prognosis of a HIV positive patient with cerebral aspergilloma is poor: there is a mortality of 85-100% [5]. This extremely high mortality is not only due to the aspergillosis infection itself, but also because aspergillosis tends to occur in cases of end-stage HIV infection. Most patients expire within two to four months after diagnosis. Therapy with Amphotericin B is advocated but has a response rate of only 20-30%.