Benign Paroxysmal Positional Nystagmus and Ototoxic Medications

Benign Paroxysmal Positional Nystagmus (BPPN) and vertigo (BPPV) is due to small crystals of calcium carbonate debris that collect within inner ear fluids. The crystals are derived from structures in the ear called "otoliths" that have been damaged by head injury, infection, other disorders of the inner ear, or age-related degeneration.

The symptoms of BPPV include brief episodes (30--40 seconds) of dizziness or vertigo, lightheadedness, imbalance, and nausea. Activities that bring on symptoms will vary in each person, but symptoms are precipitated by a position change of the head or body. Abnormal nystagmus (rapid, to-and-fro eye movements) occurs as a result of movement of the debris in the inner ear fluid. Nystagmographic criteria for BPPN include 1) latency (interval between assumption of the proper head-hanging position and nystagmus onset); 2) crescendo-decrescendo torsional or rotatory nystagmus with the upper pole of the ocular globe fast phase toward the down ear; 3) reversal of nystagmus upon sitting upright; 4)fatigability (cessation of the nystagmus 10-20 seconds after assumption of the respective head position); and 5) habituation (incremental reduction or absence of nystagmus with repetitive Hallpike tests). Clinically, BPPN is suspected when a subject complains of transient vertigo caused by or occurring after a change in the head position.

The original cause remains unknown in about half of the people with BPPV. In the other half, incidents such as head injuries may cause the disorder; among older people, it is usually caused by degeneration of the vestibular system of the inner ear. About 20 years ago, an NIH-sponsored prospective study was conducted to characterize the vestibular and auditory function of hospitalized subjects receiving medications known to be ototoxic. The subject's vestibular and auditory functions were monitored before, during and after treatment. Researchers noted a large number of subjects receiving ototoxic drugs had positive test results documenting BPPN.

The most common symptoms of developing vestibulotoxicity in an ambulatory subject are dysequilibrium, ataxia or imbalance. The vestibulotoxic subject who is confined to bed may not exhibit these or any other symptoms until becoming ambulatory. The classic symptoms of permanent vestibular ototoxicity are dysequilibrium and oscillopsia (subjective oscillation of viewed objects). Oscillopsia ("jumping" or "bobbing" of objects in the visual field) results from failure of the vestibulo-ocular reflex (VOR) to stabilize the ocular globes with respect to inertial space. This, in turn, resultants in inability to stabilize retinal images during active and passive head movements. Vertigo usually does not occur in ototoxicity unless the induced ototoxic effects are asymmetrical or if subjects undergoing ototoxic drug treatment have a preexisting vestibular asymmetry (difference in function between the two ears).

A team of researchers has set out to investigate the occurrence of BPPN in subjects undergoing treatment with potentially ototoxic medications through prospective and retrospective record reviews. The authors of "Benign Paroxysmal Positional Nystagmus in Hospitalized Subjects Receiving Ototoxic Medications," are F. Owen Black MD FACS, Susan C. Pesznecker RN, Louis Homer MD PhD, and Valerie Stallings, from the Department of Neurotology Research, Legacy Holladay Park Clinical Research and Technology Center, Portland, OR. Their findings will be presented at the annual meeting of the American Otological Society http://itsa.ucsf.edu/~ajo/AOS/aosspr2003.html held May 3-4, 2003, at the Gaylord Opryland Hotel, Nashville, TN.

Methodology: Vestibular function tests (including the "gold standard" Hallpike positional test) were performed prospectively on 225 subjects undergoing treatment of infectious disease or carcinoma with potentially ototoxic medications. Eye movements were recorded using horizontal and vertical DC-coupled electrooculography. All study subjects were hospitalized inpatients when treatment and testing were initiated. Vestibular function testing was done before or within 72 hours of drug initiation and at varying intervals afterwards. When possible, outpatient testing was conducted for one year or longer after ototoxic medication was discontinued.

A record review for positive Hallpike tests was performed on the prospective subject database, setting "Zero Time" as the start date of the ototoxic drug. Hallpike test results from 99 of the 225 study subjects were compared statistically with Hallpike test results from three other previously established subject groups.

Results: Ninety-nine of 225 study subjects underwent Hallpike testing before, during and after receiving ototoxic drugs (mostly aminoglycosides) and were included in the analysis. Forty-one (40 percent) of 99 subjects were female, 59 (60 percent) were male. Age range was 15-73 years (mean age 47 years). Major diagnostic groups included treatment of cancer, osteomyelitis, wound infection and subacute bacterial endocarditis. Study subjects received potentially ototoxic medications that included included gentamicin, tobramycin, vancomycin, streptomycin and cisplatin. In addition to parenteral medication, one subject received a single peritoneal irrigation of neomycin. Study Subjects were followed for at least one week and as long as 596 days from day zero.

Forty-nine (50 percent) of 99 Study Subjects had an unequivocally positive Hallpike test for BPPN in one or both ears. The occurrence of BPPN in the Hallpike-positive population was distributed equally across the age decades. The age range of Hallpike-positive subjects was 17-73, with a mean age of 48. Twenty-two (44 percent) of the Hallpike-positive subjects were female and 27 (56 percent) were male.. Of the 99 study subjects who underwent Hallpike testing, 49 underwent Hallpike tests within 72 hours of Day Zero, while the remaining 50 underwent Hallpike testing four or more days after Day Zero. There was no difference in occurrence of positive Hallpike responses within the two groups; 25 of 49 (51 percent) in the "baseline Hallpike" group and 24 of 50 (48 percent) in the "delayed Hallpike" group had positive Hallpikes. There was also no difference in age or gender distribution within the two groups.

Conclusions: Results of this study support the hypotheses that 1) BPPN is a common occurrence in subjects receiving ototoxic medications; and 2) BPPN may occur in normal subjects. BPPN occurrence in this study was independent of age. Within the study subjects, there was no correlation between positive Hallpike tests for BPPN and development or severity of ototoxicity.

BPPN is the most common cause of vertigo. The high occurrence rate of BPPN in subjects receiving potentially ototoxic medications is compatible with the observation that BPPN occurs in apparently normal subjects and in combination with other pathological conditions, including ototoxicity. The presence of BPPN may complicate the clinical identification of ototoxicity or obfuscate management, especially if not recognized by treating physicians. The incidence of ototoxicity may also be skewed by assuming that vertigo due to BPPN presenting during ototoxic drug administration indicates the onset of ototoxicity. The researchers recommend that subjects who receive ototoxic medication and develop vertigo be tested for BPPN if the subjects' condition permits.