Brain Pathology Case of the Month - March 2012


DIAGNOSIS

Invasive aspergillosis of the CNS with secondary hemorrhagic infarcts and subarachnoid hemorrhage in a patient with AIDS.

DISCUSSION

CNS invasive aspergillosis (IA) is often described in patients treated with intensive chemotherapy or immune suppressive therapy after solid organ or bone marrow transplantation. Patients with AIDS have a very low incidence of IA, ranging between 4 and 7% in the pre-HAART autopsy series (8,5), The low incidence of aspergillosis in the HIV population is probably the result of a relative intact phagocytic cell function in these patients. CNS invasion is even less common, reported only in 10-25% of the HIV-infected patients with IA (5). When CNS invasion occurs, it is usually in the setting of advanced HIV infection. Other major risk factors include neutropenia after ganciclovir use, high-dose corticosteroids, broad-spectrum antibiotics, and previous episodes of opportunistic infections.

Not-surprisingly, IA is often misdiagnosed or missed in the setting of HIV infection and AIDS. Generalized meningitis is a rare condition in aspergillosis, as a result, there are no abnormalities typical of Aspergillus infection in the CSF and cultures fail to grow Aspergillus. The absence of inflammation in the CSF analysis is probably the result of the hematogenous dissemination of the fungus sparing basilar meningitis. Angioinvasion, as seen in this case, is more frequently in immunosuppressed individuals. Immunocompetent patients with secondary intracranial extension after sinus or nasal infection seem to have a less aggressive form without true angioinvasion (7).

Several CNS patterns of Aspergillus lesions have been reported in the brain MRI (4). The radiological appearance of cerebral aspegillosis in patients with HIV is different from the one seen in bone marrow recipients where isointense to low signal in T1WI and contrast enhancement are more common (7,2,3,5). Solitary lesions have been described in the majority of cases (4) but it varies according to the degree of immunosupression (7). Most of the lesions are often located in the cerebral hemispheres, basal ganglia, thalami, corpus callosum and perforating artery territories (7). Involvement of the basal ganglia indicates a predominant affection of the lenticulo-striate and thalamo-perforator arteries. Callosal lesions are more often associated with toxoplasmosis, however, its presence has been previously described in IA (1) and indicates the involvement of the perforating arteries (6). The lack of contrast enhancement is typical in severe immunosupressed patients, suggesting the absence of an inflammatory response (7). The angioinvasive character of cerebral Aspergillus infection usually leads to brain infarcts with or without hemorrhage. Recently, these ischemic lesions have been described as key factor for early detection using diffusion-weighted imaging (DWI) (3,5).

Invasive aspergillosis is associated with poor prognosis among HIV-infected individuals. Mortality rate is high, reaching as much as 85 to 100% (4,7) with a mean survival time of 48 days (2). Aggressive treatment should be instituted in an attempt to decrease the high mortality. Intravenous antifungal therapy with amphotericin is ineffective in most cases. Response rates of about 35% have been achieved with voriconazole (7).

CNS aspergillosis should be considered in the differential diagnosis in patients with advanced HIV infection. Risk factors that should lead the suspicion of this condition include a very low CD4+ cell count, previous treatment with ganciclovir, valganciclovir or steroids, neutropenia, normal CSF analysis, rapidly progressive lesions in the MRI, and hyperintense lesions in the diffusion-weighted MRI.

REFERENCES

  1. DeLone DR Goldsten RA, Petermann G (1999). Disseminated aspergillosis involving the brain: distribution and imaging characteristics. American Journal of Neuorradiology 20;1597-1604.
  2. Dietrich U, Hettmann M, Maschake M, Doerfler A, Schwechheimer K, Forsting M (2001).Cerebral aspergillosis: comparison of radiological and neurophologic findings in patients with bone marrow transplantation. Eur Radiol 11:1242-1249.
  3. Gabelmann A, Klein S, Kern W, Kruger S, Brambs H-J, Rieber-Brambs A, Pauls S (2007). Relevant imaging findings of cerebral aspergillosis on MRI: a retrospective case-based study in immunocompromised patients. European Journal of Neurology 13;348-555.
  4. Hildron, A, Gongora M, Anderson A. Diazgranados C (2009). Prolonged survival of a patient with AIDS and central nervous system aspergillosis. Medical Mycology 47;327-330.
  5. Keyik B, Edguer T, Hekimoglu B (2005). Conventional and diffusion-weighted MR imaging of cerebral aspergillosis. Diagnostic and Interventinal Radiology 11;199-201.
  6. Mylonakis E, Paliou M, Sax P (2000). Central Nervous System Aspergillosis in Patients with Human Immunodeficiency Virus Infection: Report of 6 Cases and Review. Medicine 79(4);269-280.
  7. Ruhnke M, Kofla G, Otto K, Schwartz S (2007). CNS Aspergillosis Recognition, Diagnosis and Management. CNS Drugs 21;659-676.
  8. Schwartz S, Thiel E (2003). CNS-aspergillosis: are there new treatment options? Mycoses 46;8-14.

Contributed by González-Duarte, A, Saniger, M, Arispe-Angulo K, Gamboa-Dominguez A, García-Ramos, G.


International Society of Neuropathology