Journal of Neuro-Ophthalmology, March 1988, Volume 8, Issue 1

Subjective oscillopsia ("jiggling" vision) presumably due to aminoglycoside ototoxicity. A report of two cases.

Following aminoglycoside antibiotic therapy, two patients developed self-limited subjective oscillopsia in the absence of a detectable ocular motility disturbance (nystagmus or opsoclonus). Oscillopsia represents a rare, but highly distressing symptom resulting from disruption of the vestibulo-ocular reflex, producing profound illusory movement of the visual environment. Although the differential diagnosis includes vascular, inflammatory, and structural disorders impacting on either the central or peripheral projections of this brainstem reflex, iatrogenic aminoglycoside ototoxicity was the likely explanation in the two patients presented. Ways of minimizing the risk of aminoglycoside toxicity are briefly reviewed.

IO! lmal of Cli/ lical N' · / lro- ol'htl, allllo!. lgy sn I: 35- 3S, ] 9S8. .(. 19111l Raven Press, Ltd., New York Subjective Oscillopsia (" Jiggling" Vision) Presumably Due to Aminoglycoside Ototoxicity A Report of Two Cases Thomas R. Marra, M. D., Norman C. Reynolds, Jr., M. D., and Jeffrey J. Stoddard, B. s. Following aminoglycoside antibiotic therapy, two pa­tients developed self- limited subjective oscillopsia in the absence of a detectable ocular motility disturbance ( nys­tagmus or opsoclonus), Oscillopsia' represents a ra're, but highly distressing symptom resulting from disrup­tion of the vestibulo- ocular reflex, produCing profound illusory movement of the visual environment. Although the differential diagnosis includes vascular, inilamma­tory, and structural disorders impacting on either the central or peripheral projections of this brainstem reflex, iatrogenic aminoglycoside ototoxicity was the likely ex­planation in the two patients presented, Ways of mini­mizing the risk of aminoglycoside toxicity are brietly re­viewed, Key Words: Aminoglycoside antibiotic therapy- Ami­noglycoside ototoxici ty - Subj ective osci lIopsia, From the Department of Neurology, University of Wisconsin School of Medicine, Milwaukee, Wisconsin, USA. Address correspondence and reprint requests to Dr. T. R, Marra at Department of Neurology, University of Wisconsin School of Medicine, Milwaukee Clinical Campus, Mount Sinai Medical Center, 950 North 12th Street, P, O. Box 3- 42, Mil­waukee, WI 53201- 0342, U. S, A, 35 Ototoxicity of aminoglycoside antibiotics is well recognized, Such ototoxicity can manifest itself as auditory ( cochlear) dysfunction, vestibular dys­function, or both, Although previously described in the literature ( 1- 4), oscillopsia is not a widely appreciated symptom of aminoglycoside vestib­ular toxicity. Oscillopsia is a peculiar form of dis­equilibrium, characterized by a perception of ver­tical movement or " jiggling" of stationary objects. This sensation is potentiated by sudden move­ment or alteration of head posture, Despite their rather striking symptomatology, such patients may be otologically normal and without visible nystagmus or opsoclonus ( 1,2), Associated findings have notably included unsteadiness of gait and total absence of caloric responses ( 1- 3), The factor accounting for aminoglycoside- induced oscillopsia appears to be bilateral labyrinthine dys­function with resultant breakdown of the vesti­bulo- ocular retlex, a retlexive mechanism capable of generating compensatory eye movements up to 8 Hz and thereby the most important of several reflexes in maintaining visual fixation during mo­ment to moment changes of head position ( 1,3), The prognOSiS for spontaneous recovery ( or visual adaptation) is good, and the majority of patients will become asymptomatic in 3- 4 months ( 1). It is the purpose of this article to present two cases of subjective oscillopsia that developed fol­lowing aminoglycoside therapy, CASE REPORTS Case 1 A 55- year- old woman under treatment for acute myelogenous leukemia noted on discharge from 36 T. R. MARRA ET AL. the hospital that she began to have problems with her vision " jumping up and down" when she moved. The disturbance was noted 4- 5 days after discharge and occurred while walking or moving in a car. Her only other complaint was a feeling of unsteadiness on her feet. She denied weakness, confusion, diplopia, or decreased vision. She had no history of neurologic disease, otitic problems, glaucoma, eye surgery, or renal impairment. During her 24- day hospitalization, she had re­ceived cytosine arabinoside and doxorubicin, fol­lowed by gentamicin, hypercillin, vancomycin, and amphotericin- B because of sepsis. She had also been taking propranolol, Klotrix, and Estinyl. The total aminoglycoside ( gentamicin) exposure was 6.96 g ( 107 mg/ kg). Physical examination revealed normal menta­tion. Fundi were normal, and cranial nerves II through XII were intact. No nystagmus, opso­clonus, or other ocular motility disorder was vis­ible at rest or inducible with motion. Neuro- oph­thalmologic evaluation revealed mildly abnormal color vision bilaterally on pseudoisochromatic plates. Visual acuity, stereopsis, pupillary re­sponses, extraocular motility, visual fields, and funduscopic exam were all entirely normal. Opto­kinetics were 3 + in all directions. She was ortho­phoric. Reflex examination was symmetrical and normal throughout. Toes were downgoing. Motor strength was intact. There was no drift of dyssyn­ergia present. Graphesthesia, proprioception, vi­bration, and light touch were normal. No Rom­berg was present, but the patient had difficulty with tandem walk. Brainstem auditory evoked potentials of normal absolute and interpeak latency were demonstrated bilaterally. Visual evoked potentials were ab­normal due to ill- defined responses of low voltage and abnormally delayed latency bilaterally. Cere­brospinal fluid studies ( including the multiple sclerosis panel), head computed tomographic scan without contrast, and magnetic resonance scan were normal. Eight weeks after onset, the pa­tient's symptoms had largely resolved. Case 2 A 62- year- old man with renal failure requiring continuous ambulatory peritoneal dialysis for 3 years complained of a 3- week historv of acute onset visual " jiggling," ataxia, and n- ausea. He had recently been hospitalized for cardiac dys­r1,,;', n, i, Ill" h. 1,1 ,11..,,) had peritonitis ( his sixth episode) during that admission, whic~ had b~ en treated with gentamicin ( 15 mg/ 2 L peritoneal dIal­vsate), four exchanges per day for 14 days, prior to ~ dmission. On the second or third day of that hos­pitalization, he noted the visual disturbance whenever he moved his body or head honzontally or vertically. He complained of rapid movements of objects, such that he could not focus on them. He had great difficulty reading, watching televi­sion, or walking. The problem resolved if he held his head and body still and did not recur when he moved only his eyes keeping his head stationary. The patient described his gait as unsteady, with the feeling that he would topple over or fall for­ward. He also reported nausea with some emesis over the 3- week period, which responded to Com­pazine. He denied weakness, vertigo, light- head­edness, presyncope, or syncope. During his hos­pital stay, gentamicin was discontinued after 4 days. One week after discontinuation, however, gentamicin was again started ( 15 mg/ 2 L dialy­sate), with an additional 125- mg intravenous dose. After four peritoneal dialysis exchanges, genta­micin was discontinued, and tobramycin ( 15 mg/ 2 L dialysate) was administered for four exchanges. As the doses were given via the peritoneal route, the total dose of gentamicin and tobramycin cannot be calculated. The patient's past medical history notably in­cluded polycystic kidney disease and chronic bilat­eral sensorineural hearing loss without significant recent change. Other medications included cefa­zoIin, Coumadin, lidocaine, Compazine, Im­persol, Titralac, aspirin, Allbee with C, and folic acid. His symptoms did not improve following discontinuation of lidocaine. Physical examination revealed extraocular muscles intact in all directions, without horizontal or vertical nystagmus and without ocular move­ment at rest. Fundi were normal. There was no visual field defect by confrontation and no dip­lopia. Vertical and horizontal head movements produced no nystagmus, but did reproduce symptoms as given in the history. Ice water caloric testing of the left ear yielded no response whatso­ever, whereas the right ear was not tested due to tympanic membrane perforation. Markedly de­creased hearing was noted bilaterally. All other cranial nerves were intact. Motor strength was in­tact. Sensory examination revealed decreased vi­bration sense, pinprick and light touch below the knees, and temperature and proprioception were ~ ormal. Finger- to- nose and heal- to- shin were per­tormed well. Deep- tendon reflexes were sym- SUBJECTIVE OSCILLOPSIA 37 metric and toes downgoing. The examination was otherwise noncontributory. Eight weeks after discontinuation of aminogly­coside therapy, the patient remained ataxic, but his subjective visual impairment was much Im­proved, and he was able to drive a car. DISCUSSION The two patients presented in this brief report exhibited the cardinal features of oscillopsia. In both cases, symptoms developed shortly fol­lowing aminoglycoside antibiotic therapy. Pro­found subjective illusory movement of the visual environment without detectable ocular motility dysfunction ( nystagmus or opsoclonus) was en­countered. Symptoms could be provoked by mo­tion. Unsteadiness of gait was observed in each case, representing a consistent, but nonspecific, finding for oscillopsia. Both cases represen ted a largely reversible clinical syndrome. In addition to aminoglycoside- induced vestibu­lopathy, the differential diagnosis of oscillopsia encompasses other conditions impacting on either the central or peripheral projections of the vesti­bulo- ocular reflex, including various end- organ diseases, multiple sclerosis, brainstem or cere­bellar vascular disease, and encephalitis ( 3). As a subjective symptom, oscillopsia may be associated with no objective sign of an ocular motility distur­bance, and the clinician is often forced t~ relv on the patient's rather dramatic account of his'dis­tress. Under such circumstances, disease recogni­tion can be exceedingly difficult. This was particu­larly true in our first patient, who eventuallv un­derwent an elaborate diagnostic evalua'tion, including formal neuro- ophthalmologic consulta­tion, computed tomographic and magnetic reso­nance brain scanning, evoked potentials, and spinal fluid immunologic studies for multiple scle­rosis, before her condition was clarified. Evoked potentials, particularly the brainstem auditory evoked response, have been shown to have diagnostic utility in patients with suspected aminoglycoside ototoxicity and may show revers­ible abnormalities during intravenous drug infu­sion ( 5). Our first patient had a normal study. However, as the brainstem auditory evoked re­Sponse test selectively measures conduction ve­locity through the ascending auditory pathway, a normal study may have reflected the presence of selective damage to vestibular fibers with relative sparing of the cochlear system. In one study, none of 15 patients with aminoglycoside- induced oscil­lopsia demonstrated clinical hearing loss, and only 3 patients had mild audiometric evidence of hearing impairment ( 1). We were surprised to find an abnormal visual evoked potential, suggesting the presence of optic nerve dysfunction, and this finding initially led to a fruitless pursuit of diag­nostic investigations for multiple sclerosis. In ret­rospect, the abnormal visual evoked response study likely reflected the presence of an associated toxic optic neuropathy. Streptomycin has pre­viously been implicated as a cause of optic neurop­athy ( 6), and it is conceivable that other aminogly­cosides could also produce subclinical optic nerve damage. The second patient with chronic end­stage renal disease, requiring maintenance dialysis therapy, demonstrated total absence of caloric re­sponses. This parallels the experience of Ramsden and Ackrill ( 1). All 15 of their patients suffered from renal failure, and 80 C! c had no caloric re­sponse. Therapeutic considerations for the prevention of oscillopsia ( and other aminoglycoside ototoxic ef­fects) include the following: chronic renal failure patients appear to be particularly vulnerable to aminoglycoside ototoxicity, and frequent mea­surement of creatinine levels should be performed ( 7); concomitant use of loop diuretics ( especially ethacrynic acid) and aminoglycosides should be avoided ( 8,9); netilmicin has been shown to have reduced ototoxic potential relative to gentamicin, tobramycin, and amikacin ( 10- 13) and thus ap­pears to be a sound alternative agent for patients at risk. Concurrent or sequential use of more than one aminoglycoside or high total oral dosage of a single agent increases the ototoxic risk ( 7), and monitoring of peak and trough drug levels may further help to prevent ototoxicity. Elderly pa­tients or those patients with a preexisting hearing loss, severe visual impairment, or blindness mav also be at increased risk ( 8). . REFERENCES 1. Ramsden RT. Acknll D Bl) bbll1g lhCllll) p~ la trom genta­micin toxicity 81 I Audl,, 1 1982.16 1- l7- 50. , Mau AR. B~) bbing oscillllpsia . .' 11111 01,'/ Rhill"/ LII I'!/ II ,\,, 1 1' 171; 80233- 9 . , 3. Crest\' MA. Hess K, Leech J. Disorders l) f the \' estibulo- oc­ular r~ f1ex producing oscillopsla and mechanisms com pen­satll1g tor Il) S' of labvrinthine tunction. 8I'll 1/ 1 1977; 100: 6' 13- 71h. . - l. Adams RD. Victor M Prill" l!, lcs " t ' lcur" I",\ I/. Boston: 1\ kCra\\' Hill. 1981; 206. ' , 5, Cuerit ] M. Mahieu P, Houben- Cuirgea S, et al. The intlu­ence of brainstem auditof\' potentials in man. Arch Ol" rhi­! 1l'/ llryllx,,/ 1981; 233: 189- YY. 10,,, ;\ iclll't'-( lI" ltiltIllI1( ll. V" I. 8. N". 1. 1988 38 T. R. MARRA ET AL. 6. Grant WM. Toxicology of the eye. Springfield, IL: Charles C Thomas, 1974; 459. 7. 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