Pharmacotherapy of vestibular and ocular motor disorders, including nystagmus

Abstract

We review current pharmacological treatments for peripheral and central vestibular disorders, and ocular motor disorders that impair vision, especially pathological nystagmus. The prerequisites for successful pharmacotherapy of vertigo, dizziness, and abnormal eye movements are the "4 D's": correct diagnosis, correct drug, appropriate dosage, and sufficient duration. There are seven groups of drugs (the "7 A's") that can be used: antiemetics; anti-inflammatory, anti-Ménière's, and anti-migrainous medications; anti-depressants, anti-convulsants, and aminopyridines. A recovery from acute vestibular neuritis can be promoted by treatment with oral corticosteroids. Betahistine may reduce the frequency of attacks of Ménière's disease. The aminopyridines constitute a novel treatment approach for downbeat and upbeat nystagmus, as well as episodic ataxia type 2 (EA 2); these drugs may restore normal "pacemaker" activity to the Purkinje cells that govern vestibular and cerebellar nuclei. A limited number of trials indicate that baclofen improves periodic alternating nystagmus, and that gabapentin and memantine improve acquired pendular and infantile (congenital) nystagmus. Preliminary reports suggest suppression of square-wave saccadic intrusions by memantine, and ocular flutter by beta-blockers. Thus, although progress has been made in the treatment of vestibular neuritis, some forms of pathological nystagmus, and EA 2, controlled, masked trials are still needed to evaluate treatments for many vestibular and ocular motor disorders, including betahistine for Ménière's disease, oxcarbazepine for vestibular paroxysmia, or metoprolol for vestibular migraine.

Fig. 1

Effects of betahistine dihydrochloride [low dosage (filled square, dotted line): 16 or 24 mg tid versus high dosage (filled diamond, solid line): 48 mg tid] on the frequency of attacks of vertigo in 112 Ménière’s disease patients. The mean number of attacks/month (±SEM) during the 3 months preceding treatment (month 0) is indicated, as well as the number/month during therapy (month 3, 6, 9, 12). After 12 months, the mean (median) number of attacks dropped from 7.6 (4.5) to 4.4 (2.0) (p < 0.0001) in the low-dosage group, and from 8.8 (5.5) to 1.0 (0.0) (p < 0.0001) in the high-dosage group. The number of attacks after 12 months was significantly lower in the high-dosage group than in the low-dosage group (p _12M = 0.0002) (from [38])

Fig. 2

Activation of the flocculus (red) demonstrated, using fMRI, in controls vs patients for the contrast “smooth pursuit in the downward direction” (SMDOWN)—“fixation of a target in the middle of the display” (FIXMID). Results obtained by region of interest group analysis are superimposed onto orthogonal sections (a coronal plane, b sagittal plane, c axial plane) at Montreal Neurological Institute coordinates xyz = −20, −36, −40, through a standard brain template (p < 0.01). d Original recording (search-coil) of vertical pursuit (0.1667 Hz, amplitude ± 18°), which demonstrates relatively normal upward pursuit and impaired downward pursuit in a patient with DBN (from [79])

Fig. 3

Spontaneous vertical drift: vertical drift in control subjects and DBN patients due to cerebellar atrophy (DBN I), unknown etiology (DBN II), or other etiologies (DBN III) before (PRE) and after (POST) administration of 4-aminopyridine (4-AP) (gray circles target visible, black squares target blanked). DBN was reduced most in DBN I and to a lesser extent in DBN II following treatment. Similar effects were observed when the target is blanked. Error bars indicate the 95% confidence intervals (from [91])

Fig. 4

Examples of the vertical components of acquired pendular nystagmus in association with MS (a–c) and OPT (d–f). Representative records are shown when the patients were taking no treatment for their nystagmus (top panels), memantine 40 mg/day (middle panels), or gabapentin 1,200 mg/day (bottom panels). Compare the lower-amplitude oscillations at one frequency (5.6 Hz) in the patient with MS versus the larger-amplitude oscillations at lower, variable frequencies in the patient with OPT. Both drugs (especially memantine) reduce the amplitude of the oscillations in the MS patient without changing their frequency and also suppress a superimposed upbeat nystagmus. Both drugs (especially gabapentin) reduce the oscillations of OPT, which then show more cycle-to-cycle variation