Rhino-orbital-cerebral mucormycosis.

This review focuses on sinus, sino-orbital, and rhinocerebral infection caused by the Mucorales. As the traditional term of "rhinocerebral" mucormycosis omits the critical involvement of the eye, the more comprehensive term as rhino-orbital-cerebral mucormycosis (ROCM) is used. The most common underlying illnesses of ROCM are diabetes mellitus, hematological malignancies, hematopoietic stem cell transplantation, and solid organ transplantation. Sporangiospores are deposited in the nasal turbinates and paranasal sinuses in immunocompromised patients. Qualitative and quantitative abnormalities of neutrophils, monocytes and macrophages increase the risk for development of mucormycosis. Altered iron metabolism also is a critical factor in the pathogenesis of patients with diabetes mellitus who are at risk for ROCM. Angioinvasion with thrombosis and tissue necrosis is a key pathophysiological feature of human Mucorales infection. The ethmoid sinus is a critical site from which sinus mucormycosis may extend through the lamina papyracea into the orbit, extraocular muscles, and optic nerve. The brain may be seeded by invasion of the ethmoidal and orbital veins, which drain into the cavernous sinuses. Diplopia and ophthalmoplegia may be the earliest manifestations of cavernous sinus syndrome before changes are apparent on diagnostic imaging modalities. Negative diagnostic imaging does not exclude cavernous sinus mucormycosis. Mucormycosis of the maxillary sinus has a constellation of clinical features that are different from that of ethmoid sinus mucormycosis. A painful black necrotic ulceration may develop on the hard palate, indicating extension from the maxillary sinus into the oral cavity. Orbital apex syndrome is an ominous complication of mucormycosis of the orbit. Once within the orbital compartment, organisms may extend posteriorly to the optic foramen, where the ophthalmic artery, ophthalmic nerve and optic nerve are threatened by invasion, edema, inflammation and necrosis. Early diagnosis of sinus mucormycosis is critical for prevention of extension to orbital and cerebral tissues. Optimal therapy requires a multidisciplinary approach that relies on prompt institution of appropriate antifungal therapy with amphotericin B, reversal of underlying predisposing conditions, and, where possible, surgical debridement of devitalized tissue. Outcomes are highly dependent upon the degree of immunosuppression, site and extent of infection, timeliness of therapy, and type of treatment provided. New modalities for early diagnosis and therapeutic intervention are critically needed for improved outcome of patients with ROCM.