Motivation: During my final rotation in the ED, I met surprisingly many patients with sudden onset of severe unrelenting dizziness - chalked up to vestibular neuritis after clean MRI. Besides sympathetic listening and symptomatic control with meclizine, is there anything else to do? I had thought not. I recently found out, however, that steroids can help vestibular neuritis too. How good is the data?
For background, the cause of vestibular neuritis is not definitely known but based on associational data, appears related to viral infection or reactivation of latent HSV1. Symptoms of dizziness usually last three to seven days but recovery is often incomplete with many patients having persistent vestibular deficits on exam.
Paper: Strupp, M., Zingler, V.C., Arbusow, V. et. al. "Methylprednisolone, Valacyclovir, or the Combination for Vestibular Neuritis" N. Engl. J. Med. (2004) 351: 354-61.
Methods: A prospective, randomized, double-blind, 2x2 factorial trial testing methylprednisolone and valacyclovir in patients with acute vestibular neuritis. Adult patients were recruited through ED in academic hospitals in Munich and Mainz, Germany. Diagnosis of vestibular neuritis was based on history of acute onset of severe prolonged vertigo with exam showing unidirectional horizontal nystagmus with a rotational component. Patients were primarily excluded if they had additional cochlear symptoms (tinnitus or hearing loss), other brainstem deficits, central lesions on MRI, or contraindications to steroids or valacyclovir (peptic ulcer disease, osteoporosis, renal failure, liver injury, etc.). Methylprednisolone was dosed at 100 mg on first three days with a prolonged taper ending at 10 mg on day 22. Valacyclovir was dosed at 1000 mg three times daily for seven days. Primary outcome was vestibular paresis at 12 months.
Results:
Cohort: In total, 141 patients were randomized - 38 to placebo, 35 to methylprednisolone, 33 to valacyclovir, and 35 to steroid plus valacyclovir. Baseline characteristics were balanced, and average age was in late 40s for most groups. Treatment was started on average 1.6 to 1.8 days after onset of symptoms. Follow-up data present for 30/38 in placebo, 29/35 in steroids, 27/33 for valacyclovir, and 28/35 for steroid plus valacycolvir group. Most common reason for withdrawing was unwillingness to follow-up or non-compliance.
Efficacy Measurement: Change in vestibular function over time was measured by assessing nystagmus in response to caloric stimulation (warm water) in the ears. Intact vestibular response leads to appropriate nystagmus while damaged vestibular system leads to relative paresis. Analysis was by as treated and not by intention to treat population.
Steroid: At 12 months, patients receiving methylprednisolone had 62.4% improvement in vestibular function compared to 39.6% improvement with placebo (p<0.001).
Valacyclovir: At 12 months, patient receiving valacyclovir had 36% improvement in vestibular function compared to 39.6% improvement with placebo (not significant). Combination of steroid and valacyclovir resulted in 59.2% improvement in vestibular function, but the improvement was not significantly different from that achieved by steroids alone.
Discussion: This trial demonstrates that acute treatment of vestibular neuritis with corticosteroids may help prevent long-term vestibular damage. Interestingly, the authors did not track resolution of vertigo - the primary symptom that brought the patients in. The authors intentionally did not track vertigo because they assumed that the brain would compensate centrally for the imbalanced input from the two ears after a few days. Symptom improvement would not correlate with actual recovery of the vestibular system, but it would have been nice to have the data to compare. The trial also shows that valacyclovir treatment really did not affect the long-term outcome. The reason could either be that vestibular neuritis is usually not HSV mediated or that the actual reactivation and replication occurred prior to symptoms and initiation of treatment with valacyclovir. While convincing, this trial has some serious limitations including small number of subjects, no intention to treat analysis, and significant number of patients lost to follow-up in each group (17% dropout rate in steroid group). This data needs to be backed up with a larger trial. For now, though, for patients with acute vestibular neuritis with no contraindications to steroids, starting treatment early may likely have long-term beneficial effects.
For background, the cause of vestibular neuritis is not definitely known but based on associational data, appears related to viral infection or reactivation of latent HSV1. Symptoms of dizziness usually last three to seven days but recovery is often incomplete with many patients having persistent vestibular deficits on exam.
Paper: Strupp, M., Zingler, V.C., Arbusow, V. et. al. "Methylprednisolone, Valacyclovir, or the Combination for Vestibular Neuritis" N. Engl. J. Med. (2004) 351: 354-61.
Methods: A prospective, randomized, double-blind, 2x2 factorial trial testing methylprednisolone and valacyclovir in patients with acute vestibular neuritis. Adult patients were recruited through ED in academic hospitals in Munich and Mainz, Germany. Diagnosis of vestibular neuritis was based on history of acute onset of severe prolonged vertigo with exam showing unidirectional horizontal nystagmus with a rotational component. Patients were primarily excluded if they had additional cochlear symptoms (tinnitus or hearing loss), other brainstem deficits, central lesions on MRI, or contraindications to steroids or valacyclovir (peptic ulcer disease, osteoporosis, renal failure, liver injury, etc.). Methylprednisolone was dosed at 100 mg on first three days with a prolonged taper ending at 10 mg on day 22. Valacyclovir was dosed at 1000 mg three times daily for seven days. Primary outcome was vestibular paresis at 12 months.
Results:
Cohort: In total, 141 patients were randomized - 38 to placebo, 35 to methylprednisolone, 33 to valacyclovir, and 35 to steroid plus valacyclovir. Baseline characteristics were balanced, and average age was in late 40s for most groups. Treatment was started on average 1.6 to 1.8 days after onset of symptoms. Follow-up data present for 30/38 in placebo, 29/35 in steroids, 27/33 for valacyclovir, and 28/35 for steroid plus valacycolvir group. Most common reason for withdrawing was unwillingness to follow-up or non-compliance.
Efficacy Measurement: Change in vestibular function over time was measured by assessing nystagmus in response to caloric stimulation (warm water) in the ears. Intact vestibular response leads to appropriate nystagmus while damaged vestibular system leads to relative paresis. Analysis was by as treated and not by intention to treat population.
Steroid: At 12 months, patients receiving methylprednisolone had 62.4% improvement in vestibular function compared to 39.6% improvement with placebo (p<0.001).
Valacyclovir: At 12 months, patient receiving valacyclovir had 36% improvement in vestibular function compared to 39.6% improvement with placebo (not significant). Combination of steroid and valacyclovir resulted in 59.2% improvement in vestibular function, but the improvement was not significantly different from that achieved by steroids alone.
Discussion: This trial demonstrates that acute treatment of vestibular neuritis with corticosteroids may help prevent long-term vestibular damage. Interestingly, the authors did not track resolution of vertigo - the primary symptom that brought the patients in. The authors intentionally did not track vertigo because they assumed that the brain would compensate centrally for the imbalanced input from the two ears after a few days. Symptom improvement would not correlate with actual recovery of the vestibular system, but it would have been nice to have the data to compare. The trial also shows that valacyclovir treatment really did not affect the long-term outcome. The reason could either be that vestibular neuritis is usually not HSV mediated or that the actual reactivation and replication occurred prior to symptoms and initiation of treatment with valacyclovir. While convincing, this trial has some serious limitations including small number of subjects, no intention to treat analysis, and significant number of patients lost to follow-up in each group (17% dropout rate in steroid group). This data needs to be backed up with a larger trial. For now, though, for patients with acute vestibular neuritis with no contraindications to steroids, starting treatment early may likely have long-term beneficial effects.
I have read the details and found this information very useful.
ReplyDeleteThanks you for posting such information.
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