New Vestibular Neuritis Treatment Targets Assumed Etiologic Link to Herpes

Abstract & Commentary

Source: Strupp M et al. Methylprednisolone, valacyclovir, or the combination for vestibular neuritis. N Engl J Med 2004; 351:354-361.

After benign positional vertigo, vestibular neuritis is the most common cause of peripheral vestibular vertigo, with an estimated incidence of 3.5 per 100,000 in one study.1 If it is indeed a manifestation of the reactivation of herpes simplex virus type 1 infection, then corticosteroids, antiviral agents, or a combination of the two may improve the outcome. This study approached the problem using a prospective, randomized, double-blind, two-by-two factorial trial in which patients with acute vestibular neuritis were assigned randomly to treatment with placebo, methylprednisolone, valacyclovir, or methylprenisolone plus valacyclovir. Vestibular function was determined by caloric irrigation, with the use of the vestibular paresis formula to measure the extent of unilateral caloric paresis within three days after the onset of symptoms and 12 months afterward. According to the authors, the diagnosis of vestibular neuritis was based upon four criteria: 1) acute or subacute (i.e., within minutes to hours) onset of severe, prolonged rotatory vertigo, nausea, and postural imbalance; 2) horizontal spontaneous nystagmus with a rotational component toward the unaffected ear (fast phase) without evidence of a central vestibular lesion; 3) an ipsilateral deficit of the horizontal semicircular canal on the head-thrust test (performed by turning the patient’s head quickly to the right and left to elicit compensatory eye movements); and 4) a perceived displacement of verticality and the eyes rotated toward the affected ear without showing vertical divergence of one eye above the other.

There were four randomly assigned treatment groups: placebo, methylprednisolone, valacyclovir, and methylprednisolone-plus-valacyclovir. Methylprednisolone (or a matching placebo) was administered in a tapering, daily dose as follows: a single morning dose of 100 mg on days 1 through 3; 80 mg on days 4 through 6; 60 mg on days 7 through 9; 40 mg on days 10 through 12; 20 mg on days 13 through 15; 10 mg on days 16 through 18; and 10 mg on days 20 and 22. Valacyclovir (or matching placebo) was given for a week as two 500-mg capsules three times daily. The study drugs were first administered to all subjects on the day of admission, which was within three days after the onset of symptoms. Interestingly, patients also received 50 to 150 mg of dimenhydrinate a day for a maximum of three days. The list of exclusionary conditions was extensive, but properly insured that symptoms were specifically from vestibular neuritis. All patients were admitted to the hospital for at least one to seven days until they were able to walk unassisted with their eyes closed.

Of a total of 141 patients who underwent randomization, 38 received placebo, 35 methylprednisolone, 33 valacyclovir, and 35 methylprednisolone plus valacyclovir. At the onset of symptoms, there was no difference among the groups in the severity of vestibular paresis. The mean (+/-SD) improvement in peripheral vestibular function at the 12-month follow-up was 39.6 % (+/-28.1) in the placebo group, 62.4 % (+/-16.9) in the methylprednisolone group, 36.0 % (+/-26.7) in the valacyclovir group, and 59.2 % (+/-24.1) percentage points in the methylprednisolone-plus-valacyclovir group. The number of patients who had complete or partial recovery was 8 of 30 in the placebo group, 22 of 29 in the methylprednisolone group, 10 of 27 in the valacyclovir group, and 22 of 28 in the methylprednisolone-plus-valacyclovir group. That difference statistically favored the use of methylprednisolone but not valacyclovir for patients with vestibular neuritis. There were adverse effects: one patient with a bleeding ulcer, two patients with hyperglycemia, and five patients with mood swings in the methylprednisolone groups; no adverse effects occurred in the placebo or valacyclovir-only group.

Commentary by Richard Hamilton, MD, FAAEM, ABMT

This study is well constructed and clearly points to a therapeutic value for steroids in vestibular neuritis. I am a little curious about the effect that dimenhydrinate had on symptoms, but this is not reported despite the fact that it is a potential confounder to the data. The large and sustained dose of methylprednisolone, the frequent complications, and the authors’ meticulous evaluation and screening of the patients suggest that this is a therapy that should be initiated in consultation with a neurologist and requires admission to a hospital. However, there is much room for an ED-based study that evaluates the role of shorter courses and smaller doses of steroids for this condition. ED physicians should be aware of this new therapy and consult an informed neurologist to consider this treatment for patients suffering from acute vestibular neuritis.

Dr. Hamilton, Associate Professor of Emergency Medicine, Residency Program Director, Department of Emergency Medicine, Drexel University College of Medicine, Philadelphia, PA, is on the Editorial Board of Emergency Medicine Alert.

References

1. Sekitani T et al. Vestibular neuronitis: Epidemiological survey by questionnaire in Japan. Acta Otolaryngol Suppl 1993;503:9-12.