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

• Published in: The Tohoku Journal of Experimental Medicine Vol. 203; no. 2; pp. 133 - 139
• Main Authors: Yamanoi, Takahiko, Shibano, Ken, Soeda, Tomoko, Hoshi, Akihiko, Matsuura, Yutaka, Sugiura, Yoshihiro, Endo, Kazuhiro, Yamamoto, Teiji
• Format: Journal Article
• Language: English
• Published: Japan Tohoku University Medical Press 01-06-2004
• Subjects: Aged; Antifungal Agents - therapeutic use; antifungal therapy; Eye - microbiology; Eye - pathology; Female; fungus infection; Humans; intracranial aspergillosis; itraconazole; Itraconazole - therapeutic use; Magnetic Resonance Imaging; Male; Middle Aged; Neuroaspergillosis - drug therapy; Sphenoid Sinus - microbiology; Time Factors
• ISSN: 0040-8727; 1349-3329
• DOI: 10.1620/tjem.203.133

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.