title: Intracranial invasive aspergillosis originating in the sphenoid sinus: a successful treatment with high-dose itraconazole in three cases.
abstract: 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.
authors.affiliation: Department of Neurology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan. yamanoi@fmu.ac.jp
authors.forename: Takahiko
authors.initials: T
authors.lastname: Yamanoi
authors.forename: Ken
authors.initials: K
authors.lastname: Shibano
authors.forename: Tomoko
authors.initials: T
authors.lastname: Soeda
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hoshi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Matsuura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sugiura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Endo
authors.forename: Teiji
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D005123:Eye / Q000382:microbiology / Q000473:pathology; D005260:Female; D006801:Humans; D017964:Itraconazole / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020953:Neuroaspergillosis / Q000188:drug therapy*; D013101:Sphenoid Sinus / Q000382:microbiology*; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole