Tohoku J. Exp. Med., 2004, 203(2)

Case Report

Intracranial Invasive Aspergillosis Originating in the Sphenoid Sinus: A Successful Treatment with High-Dose Itraconazole in Three Cases

TAKAHIKO YAMANOI, KEN SHIBANO, TOMOKO SOEDA, AKIHIKO HOSHI, YUTAKA MATSUURA, YOSHIHIRO SUGIURA, KAZUHIRO ENDO and TEIJI YAMAMOTO

Department of Neurology, Fukushima Medical University School of Medicine, Fukushima 960-1295

We report three cases of intracranial aspergillosis originating in the sphenoid sinus in immunocompetent patients. The patients presented with an orbital apex syndrome in that a unilateral loss of vision and cranial nerve III palsy were seen in all cases and a contralateral involvement was also seen in one case. Despite the initial treatment with a conventional dose of itraconazole (ITCZ, 200 mg/day), the neurological deficits failed to improve and the granulomatous inflammation was not suppressed. Therefore, we treated with a combination of a high dose of ITCZ at 500-1000 mg/day (16-24 mg/kg/day) and amphotericin B (AMPH-B) at 0.5 mg/kg/day, in conjunction with a pulse dose of methylprednisolone at 1000 mg/day. Two cases responded favorably in that the ocular movements completely recovered, and their maximum serum concentrations of the hydroxy ITCZ were 7816 ng/ml and 5370 ng/ml. However, the other case worsened, despite ITCZ treatment at 16 mg/kg/day, and the serum concentration of the hydroxy ITCZ was 3863 ng/ml. The surgical decompression of the cavernous sinus via an extradural approach was performed, and the dose of ITCZ was increased to 24 mg/kg/day. The resulting serum concentration of the hydroxy ITCZ was 4753 ng/ml, and the outcome of this case has been favorable. These results suggest that a high blood level of the hydroxy ITCZ (more than 4500 ng/ml) is a prerequisite for the successful treatment of intracranial aspergillosis and that the combination treatment of ITCZ with AMPH-B would be preferred. The concomitant use of steroid and/or surgical decompression should be considered, if the invasiveness is not well-controlled in spite of intensive medical therapy.

keywords —— intracranial aspergillosis; itraconazole; antifungal therapy; fungus infection

© 2004 Tohoku University Medical Press

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Address for reprints: Takahiko Yamanoi, Department of Neurology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Japan.

e-mail: yamanoi@fmu.ac.jp