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(36.8%) patients with no identifiable cause for immunosuppression.Magnetic resonance imaging (MRI) was done in all the patients. Paranasal sinusitis with orbital involvement was noted in 26 (68.4%) patients. Intracranial extension was noted in 12 (31.6%) patients. Cavernous sinus involvement was noted in six and suprasellar extension in two patients. Stroke secondary to probable vasculitis was seen in 12 patients - 11 had internal carotid artery (ICA) stroke (bilateral involvement in two) and one had posterior cerebral artery (PCA) stroke. Four patients had intracranial abscess [Figure - 1] (bifrontal -one, temporal lobe-one, capsuloganglionic -one and cerebellopontine angle-one). All the patients underwent spheno-ethmoidectomy and or maxillectomy according to the involvement. Radical surgery (enucleation of eye, orbital exenteration, craniotomy with debridement, extensive craniofacial resection and reconstruction,) was done in 18 (47.4%) patients.The diagnosis of fungal infection was based on direct microscopy of the tissue from the nasal/sinus mucosa or the intracranial mass lesion and histopathology. Zygomycetes and Aspergillus were the commonest organisms found in 18 (47.4%) and 16 (42.1%), respectively [Figure - 2],[Figure - 3]. Melanized fungi was found in two and mixed Aspergillus and Zygomycosis in two patients. The culture was done in 21 cases and it was positive in 12 ( aspergillus species in five, rhizopus in six and cladosporium in one). Aspergillus flavus was isolated in three, Aspergillus fumigatus and Aspergillus terreus in one each. Among those with culture-positive zygomycosis , Rhizopus oryzae was isolated in five and rhizomucor in one patient. Culture was positive in one patient with pheohyphomycosis and basal ganglionic abscess and cladosporium species was isolated.All these patients were treated with amphotericin B. In addition six patients with Aspergillosis received 5-flurocytosine. The total dose of amphotericin B given ranged from 3-6 g. Liposomal amphotericin (Ambisome) was given to seven patients and the total dose given in each patient was 3 g. One patient with rhinoorbitocerebral mixed Aspergillus and Zygomycosis infection and a temporal lobe fungal abscess, did not respond to liposomal amphotericin. Mixed zygomycosis and aspergillus infection was identified on tissue morphology, but culture isolated Aspergillus fumigatus only. He was given intravenous voriconazole 400 mg/day for two weeks followed by oral voriconazole 400 mg/day for six months. The patient improved markedly at the end of one year with no residual neurological deficits and near total resolution of the temporal lobe abscess on MRI [Figure - 1]. The common complications during treatment with amphotericin B were hypokalemia in 30 (78.9%), acute renal failure in four (10.5%), hyponatremia in two (5.3%) and symptomatic hypomagnesemia in three (7.9%). The duration of hospital stay in the survived group was 21-123 (mean 56) days.All the patients underwent follow-up MRI of brain and sinuses (plain and contrast) for the resolution of the lesions. Repeat biopsy/aspiration cytology was done in 12 patients who survived and no fungal elements could be demonstrated on pathology. The follow-up ranged from one to nine years. Eighteen (47.4%) patients died. Elderly patients (age > 60 years) had a mortality of 58.3% compared to 36.4% in adults (age 17-59) and the difference was not statistically significant ( P ≤ 1). There was no statistically significant difference in mortality between males (46.6%) and females (50%) with P ≤ 1. Patients with focal neurological deficits had higher mortality (75%) compared to those without focal deficits (34.6%) and the difference between the two groups is statistically significant ( P < 0.025). The mortality was higher in patients with immunocompromised state (56.5%) compared to those with immunocompetent state (33.3%) but the difference was not statistically significant ( P ≤ 0.2). No significant difference in mortality was noted between the patients who underwent radical surgery (44.4%) and no radical surgery (50%), P ≤ 1. Among the 10 patients who did not undergo radical surgery six patients died due to associated medical complications like septicemia in three, massive upper gastrointestinal bleed in one, acute renal failure in one and myocardial infarction in one. One patient had subarachnoid hemorrhage before death. The mortality was higher in rhinocerebral syndrome due to Zygomycosis (62.5%) than with Aspergillus (38.9%), but the difference was not statistically significant ( P£0.2).
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