Rinsho Shinkeigaku (Clinical Neurology)

Case Report

The effects of voriconazole and vascular lesions in invasion of aspergillosis into the central nerve system

Asako Ueno, M.D.1), Tadanori Hamano, M.D.1), Akihiro Fujii, M.D.1), Akiko Matsunaga, M.D.1), Seiji Naganuma, M.D.2), Makoto Yoneda, M.D.1), Hiroshi Itoh, M.D.2) and Masaru Kuriyama, M.D.1)

1)Second Department of Internal Medicine (Division of Neurology), Faculty of Medical Sciences, University of Fukui
2)Department of Pathological Science (Division of Tumor Pathology), Faculty of Medical Sciences, University of Fukui

We report 2 patients showing invasion of aspergillosis into the central nerve system (CNS). Patient 1, an 81-year-old woman, underwent surgery for sphenoidal sinusitis. She developed cerebral infarction with unconsciousness on 12th postoperative day. CSF examination demonstrated pleocytosis with increased protein and aspergillus antigen. She was diagnosed as having invasion of aspergillosis into the CNS, and was treated with voriconazole. Her clinical manifestations and CSF findings markedly improved. However, the effects of voriconazole gradually attenuated and she demonstrated recurrence of the cerebral infarction. After 2 months, she died of systemic aspergillosis and sepsis. Autopsy studies. Severe atherosclerotic changes with calcification were demonstrated in the bilateral carotid and basilar arteries, and many aspergillus were clustered in the vessel walls. Granulomatous inflammatory lesions with aspergillus were also demonstrated in the area surrounding the chiasm. There were no massive infarcts or bleeding in the brain, but multiple small infarcts were present. Patinet 2, a 64-year-old man, showing bilateral visual loss, was receiving treatment with corticosteroids under a diagnosis of optic neuritis. Two weeks later, he developed cerebral infarction. CSF examination showed pleocytosis with increased protein and aspergillus antigen. He was diagnosed as having invasive aspergillosis from the sphenoidal sinusitis into the CNS. He was treated with voriconazole, and unconsciousness and CSF findings improved transiently. However, he developed a recurrence of the brain infarction and pneumonia and finally died 6 months later. Treatment by voriconazole was definitely effective in both patients, but both patients died of recurrent cerebral infarction, possibly due to resistance for voriconazole, or developing multicellular filamentous biofilms. Voriconazole is recommended as the first choice of antifungal agents for aspergillosis. Aspergillus infection is strongly invasive into arterial vessels. It is important to consider the possible occurrence of cerebrovascular disease when treating invasion of aspergillosis into the CNS.
Full Text of this Article in Japanese PDF (892K)

(CLINICA NEUROL, 49: 468|473, 2009)
key words: central nervous system aspergillosis, voriconazole, sinusitis, cerebrovascular disease

(Received: 14-Oct-08)