Intracranial complications of mucormycosis: An experimental model and clinical review

Abstract

The clinical course of patients with mucormycosis of the paranasal sinuses can be unpredictable and is often determined by intrinsic host factors. The degree to and mechanism(s) by which these factors influence a patient's ability to survive the disease are poorly understood. Extensions to orbital and intracranial structures occur in some patients with paranasal sinus mucormycosis despite aggressive treatment. Controversies persist over adequate antifungal regimen, the precise role of hyperbaric oxygenation, and the appropriate extent of surgical debridement. We have developed an alloxan-induced immunocompromised murine model of mucormycosis in mice. Deferoxamine iron chelation produced rhinocerebral mucormycosis in these animals when challenged intraethmoidally with Rhizopus spores. The implications of our experimental studies in the content of our clinical experience in managing patients with intracranial extensions of paranasal sinus mucormycosis are discussed.

Zygomycetes in Human Disease

“…In the guinea pig model, ad- Hyphal type Aseptate or nearly aseptate hyphae; may also present as gnarled or "crinkled cellophane" balls in specimens ministration of deferoxamine and iron in experimentally infected animals lead to decreased survival and decreased response to amphotericin B (470). The presence of acidosis together with deferoxamine therapy may also be a fatal combination (15). By inhibiting the binding and sequestration of iron by transferrin, acidosis also serves to keep the concentrations of iron in the plasma high, allowing its use as a growth factor by the zygomycetes (23).…”

“…Rhizopus spp. reportedly have an active ketone reductase system (15). This may act as an additional virulence factor for these organisms, permitting them to grow well in the acidic and glucose-rich environment seen in ketoacidotic states.…”

Current Perspectives on Ophthalmic Mycoses

“…Various zygomycetes are reported to cause rhino-orbito-cerebral zygomycosis (15,435). Criteria for diagnosis include suggestive clinical features; detection of the characteristic large, broad aseptate hyphae in necrotic material or tissue bits or sections; and growth on multiple culture media.…”

“…Spherical, multinucleate yeast-like cells (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) m in diameter) with single broad-based bud and refractile double-contoured walls; generally larger than those of cryptococci (301). Seen in KOH mounts of necrotic material or in tissue sections, and generally extracellularly (215,338), and in culture at 37°C.…”

Rhinocerebral Mucormycosis

“…Gregory et al in 1943 first described three fatal cases of cerebral mucormycosis. 17 The disease rapidly spreads to the orbit 18 and brain 19,20 and is eventually fatal unless clinical recognition is early and specific treatment is instituted rapidly. In our series, the diagnosis was delayed and contributed to the poor prognosis.…”