Vestibular and hearing manifestations of phenytoin toxicity: A retrospective series

Ear, Nose & Throat Journal, June, 2001 by Juan I. De Diego, Maria P. Prim, Sol Marcos, Maria J. De Sarria, Javier Arpa, Javier Gavilan

Abstract

We undertook a study to identify the vestibular and hearing abnormalities associated with phenytoin toxicity. Since October 1977, 23 patients with phenytoin toxicity have been referred to the Department of Otorhinolaryngology by the Department of Neurology for electrooculographic (EOG) evaluation. (There have been no cases of serious phenytoin toxicity seen in our department since August 1989.) In addition to EOG, all patients had undergone otoscopic, audiometric, and neurologic examinations. We found that the most common pathologic findings detected by EOG were abnormalities in pursuit tracking. The most common signs found on clinical exploration were cerebellar dysfunction and facial palsy. EOG findings in patients with phenytoin toxicity are compatible with cerebellar disease.

Introduction

Phenytoin (diphenylhydantoin) is one of the most widely used anticonvulsants, particularly in the acute and chronic management of epilepsy in children and adults. This drug is remarkably free of serious side effects, [1] although toxic blood levels can cause adverse neurotologic effects. [2] Long-term therapy has been reported to cause cerebellar atrophy in humans. [3] Adverse effects in experimental animals have included a loss of Purkinje's cells, edema of Bergmann's glial cell layer, and degenerative cell changes. [4] The primary signs and symptoms of toxicity are shown in table 1. [1,5-13] Generally, all these effects are reversible and disappear after a reduction in dosage or cessation of the drug, except for chronic cerebellar ataxia secondary to long-term phenytoin intake, which is considered to be irreversible. [2] The aim of our study was to identify the vestibular and hearing abnormalities associated with phenytoin toxicity.

Materials and methods

Since October 1977, 23 patients with phenytoin toxicity have been referred to the Department of Otorhinolaryngology by the Department of Neurology for electrooculographic (EOG) evaluation. (There have been no cases of serious phenytoin toxicity seen in our department since August 1989.) The diagnosis of phenytoin toxicity had been made in the Department of Neurology according to the presence of certain clinical manifestations (table 2). According to our retrospective chart review, the 15 female and 8 male patients ranged in age from 13 to 64 years (mean: 34.6). Otoscopy, audiometry, a basic neurologic exploration, and an EOG examination had been performed on all subjects. Since 1985, it has been possible to obtain blood phenytoin levels at our hospital, and this information was included in the records of 8 patients who had been seen after 1985.

During the EOG examination, eye movements were registered by a Grass polygraph (model 79D) and DC register, with an upper cutoff frequency of 75 Hz. Monocular horizontal eye movements were measured with surface electrodes fixed medially to the inner canthus and laterally to the outer canthus of each eye. A pair of vertically fixed electrodes attached over the eyebrow and below the lower eyelid was used to detect blink artifacts and vertical nystagmic components. Each patient was evaluated for saccades, spontaneous nystagmus, response to rotational and positional tests, vestibulo-ocular reflex suppression, optokinetic nystagmus, and pursuit tracking. Saccades were studied with an alternating luminous point that was driven by an OK4 generator (ServoMed). Spontaneous nystagmus was registered with closed eyes. Rotational tests were conducted with a diminished pendular stimulus; at the same time, vestibulo-ocular reflex suppression was registered with the patient's gaze fixed on a point that moved simultaneously w ith the pendular motion. Optokinetic nystagmus was stimulated with a rotating drum that was electrically controlled at two different speeds: 30[degrees] and 150[degrees]/sec. All results were analyzed by the Department of Research at our institution.

Results

We found no hearing impairment in any of these patients. The most common clinical findings were cerebellar signs and facial palsy. On EOG, the most common pathologic findings were abnormalities in pursuit tracking. We saw no case of diplopia or impairment of the IIIrd, IVth, or VIth cranial nerves. Details:

* Only 1 patient had an abnormal otoscopic examination (4.4%).

* There were 13 vestibular and auditory complaints: 8 cases of dizziness (34.8%), 3 of vertigo (13.0%), and 2 of hypoacusis (8.7%). There were no cases of algiacusis or tinnitus.

* The results of clinical exploration are shown in table 3.

* EOG revealed that 1 patient (4.4%) had dysmetric saccades; saccades were normal in the remaining patients.

* Spontaneous nystagmus was found in 3 patients (13.0%); 2 had periodic alternating nystagmus, and 1 had gaze-evoked horizontal nystagmus.

* During the rotational test, abnormalities were registered in 7 patients (30.4%); 2 had a left preponderance, 1 had bilateral hyperreflexia, 3 had bilateral hyporeflexia, and 1 had an atypical morphologic pattern. Only 1 patient exhibited alterations during the positional test; this patient had a type II recording according to Arslan's method.