Gentamicin-Induced Bilateral Vestibular Hypofunction

Abstract

A65-year-oldmanwasreferredtoThe Johns Hopkins Hospital Oncology Service for treatment of acute myelogenous leukemia. On admission, he had fevers, neutropenia, and erythematous papular lesions of the face and left antecubital fossa. Acinetobacter was cultured from his blood. Treatment included vancomycin, ciprofloxacin, and a 3-week course of gentamicin at a dose of 1.7 mg/kg intravenously every 8 hours. Predose and peak postdose gentamicin levels were checked on 4 occasions during treatment and never exceeded the therapeutic range, which is less than 2.5 mg/L within 30 minutes predose and less than 10 mg/L 1 hour postdose. On the fourth day ofbroad-spectrumantibiotic therapy, induction chemotherapy was begun with cytarabine,daunorubicin,andetoposide. Duringthisperiodthepatientdeveloped Aspergillus pneumonia requiring treatment with amphotericin B. The patient’s condition improved, and a bone marrow aspirate about 30 days intothe inductionchemotherapyshowed that his leukemia was in remission. He was discharged to finish his course of intravenous amphotericin B at home. Six weeks after discharge, he was readmitted to Johns Hopkins for consolidation chemotherapy with cytarabine and daunorubicin. Although he had received prophylactic antimicrobial coverage with vancomycin and acyclovir, he developed fevers during the neutropenic phase of his treatment. The fevers were managed with gentamicin (1.7 mg/ kg intravenously every 12 hours) and piperacillin. During this 2-week gentamicin course, predose and peak postdose levels were again checked 4 times and foundtobewithinthetherapeuticrange. As the patient improved over the next 2 months, he noted new unsteadiness and constant disequilibrium. Head movements worsened these symptoms and caused oscillopsia. When he sat with his head still, however, he had no vertigo and minimal complaints about balance or equilibrium. He was referred for a vestibular evaluation. On physical examination, his extraocular movements were intact, with no spontaneous or gaze-evoked nystagmus when examined under Frenzel lenses (magnifying glasses that prevent the patient from fixating). Saccades, smooth pursuit, and vergence eye movements werenormal.Hisvestibulo-ocularreflex inresponsetohigh-accelerationhorizontal head thrusts (rapid “doll’s head” maneuvers)wasdiminished.Thisreduction was so severe that he had to make compensatory saccades to maintain fixation on a still object. On evaluation of posture and gait, the patient was able to maintain a Romberg position for longer than 15 seconds. He was unable to maintain a tandem Romberg position (standing with 1 foot in front of the other, thereby narrowing his base of support) with his eyes open or closed. His gait was moderately ataxic, with an uneven cadence and eyes fixed on the ground. When he tried to walk with his eyes closed or to turn while walking, he was markedly unsteady and would have fallen without support from the examiner. Calorictestingonelectronystagmography showed no responses to warm (44°C) or cold (31°C) irrigations of each ear. Icewater caloric testing evoked a left-beating nystagmus with slow-phase eye velocity of 6° per second for irrigation of the right ear and a right-beating nystagmus withslow-phaseeyevelocityof7°persecond for irrigation of the left ear. Rotatory chair testing showed abnormally low vestibulo-ocular responses. Computerized dynamic posturography showed loss of balance in test conditions in which only vestibular information had the potential for maintaining balance. The patient was treated with a course of vestibular rehabilitation exercises designed to improve his balance control by strengthening his reliance on visual and somatosensory inputs alone. One year later, his leukemia remained in remission. He had resumed relatively normal physical activity, although quick head movements still caused him to lose his balance.