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Our objective was to discuss the management and outcome of abducens nerve palsy in patients with Gradenigo's syndrome. In a retrospective analysis of patients with Gradenigo's syndrome at a tertiary-care center in Houston, Texas, from 1987 to 1995, we identified 2 patients with Gradenigo's syndrome, both female. One had bilateral involvement, so that the total was 3 ears. Both patients had complete recovery of their abducens nerve palsy. In 2 ears with chronic mastoiditis, sixth nerve palsies failed to respond to medical therapy alone, but resolved after mastoidectomy with drainage of the petrous apex. We recommend that patients with Gradenigo's syndrome and evidence of chronic mastoiditis be treated with aggressive medical and surgical care.

Cholesteatoma matrix and tympanic epithelia share the unique property of en mass migratory locomotion in vitro. Although this migratory behavior is not well understood, it is thought to be a major contributor to the pathogenesis and pathophysiology of cholesteatoma disease. We have surmised that en mass migration depends on tight calcium-dependent intercellular and substrate cellular adhesions. The purpose of this investigation was to determine the effects of a diminished extracellular calcium level on cholesteatoma migration and adhesion. Cholesteatoma matrixes obtained intraoperatively from patients undergoing mastoidectomies for chronic ear disease were cut into small fragments and grown in culture. When cultured specimens were exposed to low-calcium medium (0.14 mmol/L calcium), a greater than 10-fold reduction in the rate of migration was observed when compared with control values (1.8 mmol/L calcium). This reduction of migration returned to normal within 48 hours after extracellular calcium was replenished. Substrate cellular adhesion was also significantly reduced when cholesteatoma cells were grown in low-calcium medium. These observations were further supported by histomorphologic findings. Our findings suggest that calcium-dependent intercellular and substrate cellular adhesions are essential for cholesteatoma migration and adhesion. These studies further our understanding of the pathophysiology of cholesteatoma disease and may provide clues on how to better treat patients with this disease.

Retinoids have recently become of interest to clinicians because of their ability to inhibit migration and proliferation of premalignant squamous cells while enhancing growth and proliferation of normal cells. An in vitro investigation was undertaken to determine whether retinoic acid exhibits similar inhibitory effects on cholesteatoma cells. Cholesteatoma specimens were obtained intraoperatively from 10 patients undergoing mastoidectomy or revision mastoidectomy for chronic ear disease. Cholesteatoma explant growth and en mass migration were observed daily, and topographic maps were constructed at various time intervals to quantity rate and direction of explant migration in the presence or absence of all-trans retinoic acid. Before all-trans retinoic acid administration, explants migrated very rapidly (1 to 2 mm/day). A maximum threefold inhibition of migratory rate occurred, with explants exposed to 0.1 micromol/L retinoic acid when compared with controls. A sixfold maximum inhibition was observed at higher retinoic acid concentrations (5 micromol/L). On removal of all-trans retinoic acid, twofold and fourfold increases in migratory rates were observed. The direction of explant migration varied significantly for long periods of time and appeared not to be affected by retinoic acid. This investigation suggests that all-trans retinoic acid has an inhibitory effect on cholesteatoma cell migration. Retinoids may have a role in controlling cholesteatoma disease in the future.