by Elena Moro
For January 2017, we have selected: Patel M, Agarwal K, Arshad Q, et al. Intratympanic methylprednisolone versus gentamicin in patients with unilateral Ménière’s disease: a randomized double-blind, comparative effectiveness trial. Lancet Neurol 2016;388:2753-2762.
Disabling vertigo attacks and hearing loss are characteristics of Ménière’s disease. In patients with severe and frequent vertigo spells, intratympanic injections of gentamicin have proved to be effective, but at the price of permanent vestibular damage and hearing loss. Corticosteroids have also been used with benefit, but solid clinical evidence is lacking.
In this dual-center UK study the efficacy of gentamicin versus methylprednisolone in reducing the number of vertigo attacks in the final 6 months of the treatment was assessed in a double-blind randomized fashion. Sixty patients with definite unilateral Ménière’s disease, and at least two episodes of vertigo lasting ≥20 minutes in the previous 6 months were enrolled over a 4-year period. Patients were randomized to receive two intratympanic injections (separated by a 2-week interval) as outpatients. Follow-up visits were scheduled at 1, 2, 6, 12, 18, and 24 months. Before the second injection patients underwent an audiogram that was read by a masked clinician, and sent directly to the pharmacist, who could switch gentamicin to saline if patients had a 20 dB drop in hearing through any two consecutive frequencies. In non-responder patients, an unmasked clinician could prescribe further injections, keeping blindness for treatment allocation. Patients were asked to complete a short form Vertigo Symptom Scale (VSS), the Dizziness Handicap Inventory, and other quantitative scales. Pure tone audiometry, speech discrimination, and vestibular function were assessed at almost each follow-up visit. The primary analysis was based on ANOVA model and intention-to-treat population.
Thirty patients were allocated to gentamicin and 30 to methylprednisolone. Between 18 and 24 months after the first injections, 19 patients (63%) in the former, and 20 (67%) in the latter group had no vertigo attacks. There was no difference between drugs in the odds of presenting with vertigo attack in the last 6 months of the study (OR 1.2, 95% CI 0.4-3.3; p=0.79). There was a significant improvement in vertigo spells frequency with both drugs compared to before the treatment (from 19.9 to 2.5, 87% reduction with gentamicin, and from 16.4 to 1.6, 90% with methylprednisolone, p<0.0001). No significant differences were found between the two drugs for most scales and assessments, except for speech discrimination, which more improved in the methylprednisolone group. There were no differences in the number of non-responders; in the methylprednisolone group 15 patients needed further injections versus eight in the gentamicin group.
The most common AE was minor ear infections (five patients in total). Before the second injection, nine patients with gentamicin and five with methylprednisolone had hearing loss. Vestibular function was significantly better in the methylprednisolone group.
“This is the first study comparing efficacy and side effects of intratympanic injections of gentamicin versus methylprednisolone in patients with unilateral refractory Ménière’s disease over a 2-year period”, says Prof. Marianne Dieterich, Department of Neurology, University of Munich, Germany. “Overall, both treatments were highly effective in reducing vertigo attacks. However, since methylprednisolone does not have ototoxic properties, it was associated with preserved vestibular function.”
“This study nicely confirms our experience. Intratympanic gentamicin should only be used after unsuccessful repeated intratympanic methylprednisone injections”, says Prof. Dominik Straumann, Department of Neurology, University Hospital Zurich, Switzerland.
The other nominee for the January paper of the month is:
Schonenberger A, Uhlmann L, Hacke W, et al. Effect of conscious sedation vs general anesthesia on early neurological improvement among patients with ischemic stroke undergoing endovascular thrombectomy. A randomized clinical trial. JAMA 26 Oct 2016;doi:10.1001/jama.2016.16623. In this “SIESTA” (Sedation vs Intubation for Endovascular Stroke Treatment) study 150 patients with ischemic stroke in the anterior circulation were randomized to receive thrombectomy under general anesthesia or during nonintubated conscious sedation. Early neurological improvement on the NIHSS score was considered as primary outcome. At 24 hours, there was no better improvement in the conscious sedation group vs the general anesthesia group.