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 wellcontrolled in spite of intensive medical therapy. intracranial aspergillosis; itraconazole; antifungal therapy; fungus infection

Comparison of Efficacy of Amphotericin B and Itraconazole in Chronic Invasive Fungal Sinusitis

“…Despite a long course of treatment the compliance of the patients was good with itraconazole. We used conventional doses of itraconazole (4-6 mg kg body weight per day).Yamanoi et al [14], has used high dose of itraconazole (16-24 mg/kg) in his study with few side effects. Due to erratic bioavailability of itraconazole serum drug concentration monitoring has been advised.…”

Natural Course of Hematoma in Lateral Rectus Muscle Followed by Magnetic Resonance Imaging

“…Severe orbital apex syndrome with EMD and reduced vision caused by aspergillosis might need emergency treatments of antifungal therapy, steroid, and surgical decompression (Yamanoi et al 2004). On the other hand, a spontaneous orbital hemorrhage is a rare condition that causes acute ocular pain, exophthalmos, EMD, diplopia, and reduced vision (Shimura et al 1992).…”

Chronic invasive sinus and intracerebral aspergillosis controlled by combination therapy with micafungin and a daily dose of 400 mg itraconazole oral solution

“…Furthermore, a series of three cases of chronic invasive aspergillosis of the sinus showed that high-dose ITCZ therapy is effective [8]. These three cases were treated only with high-dose ITCZ capsules.…”