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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 24  |  Issue : 3  |  Page : 135-138

Is there enough evidence to refute the antiviral therapy in vestibular neuritis: A best evidence review


Department of Otorhinolaryngology and Head and Neck Surgery, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India

Date of Web Publication11-Jan-2019

Correspondence Address:
Dr. K Devaraja
Department of Otorhinolaryngology and Head and Neck Surgery, Kasturba Medical College, Manipal - 576 104, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/indianjotol.INDIANJOTOL_13_18

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  Abstract 


Background: Recent research has provided extended support on the viral etiology of vestibular neuritis (VN); however, antiviral therapy is considered non-beneficial helpful in VN, contrary to its role in other similar viral-induced inflammatory conditions. The objective of this review is to segregate the available literature on antiviral therapy in VN and to evaluate and analyze the results of all those studies to know whether the antiviral therapy helps in VN patients or not. Materials and Methods: Electronic databases searched include PubMed, Scopus, Web of science, IndMED, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane library. Study Selection: Prospective randomized controlled trials (RCTs) comparing the outcomes of any form of antiviral therapy in VN, with that of placebo or any form of steroid or any other alternative therapy. Data Extraction and Data Synthesis: Among 581 screened articles, only one RCT was found on this topic, precluding the meaningful statistical analysis. However, this study did not consider the symptomatic improvement after antiviral therapy but only reported caloric response which is of less clinical relevance. No other controlled prospective study on antiviral therapy in VN has been published. Conclusions: The available evidence is not sufficient to disregard the beneficial effect of antiviral therapy in VN. Further randomized trials with better and clinically relevant study design are required to answer the question.

Keywords: Antiviral therapy, vestibular neuritis, vestibular neuronitis


How to cite this article:
Devaraja K. Is there enough evidence to refute the antiviral therapy in vestibular neuritis: A best evidence review. Indian J Otol 2018;24:135-8

How to cite this URL:
Devaraja K. Is there enough evidence to refute the antiviral therapy in vestibular neuritis: A best evidence review. Indian J Otol [serial online] 2018 [cited 2019 May 26];24:135-8. Available from: http://www.indianjotol.org/text.asp?2018/24/3/135/249868




  Introduction Top


Vestibular neuritis (VN) is the most common peripheral cause of vertigo in adults, after benign paroxysmal positional vertigo.[1] Pathophysiologically, it is nothing but the inflammation of the vestibular nerve which hampers the ipsilateral vestibular function. The reported incidence of VN is around 3.5 cases in 100,000.[1] Typical symptoms include sudden onset of severe rotatory giddiness lasting for days, associated with nausea and vomiting, without any hearing impairment. On examination, the affected individual would have spontaneous nystagmus with fast component toward the uninvolved side, along with the abnormal head impulse test and the ipsilateral canal paresis.[2] In general, the acute symptoms of VN improve within few days and the balance gets resorted by the virtue of signals from proprioception and vision, supplemented by central vestibular compensation.[3],[4] The peripheral vestibular function on the affected side also tends to recover in nearly half of the patients, in the form of improved canal response.[2],[5],[6] However, many of these individuals continue to experience episodic giddiness for years, which is attributed to reactivation of latent virus in vestibular ganglia.[7],[8],[9]

Although the etiology of VN is elusive, a viral infection of the vestibular ganglia is the most probable cause of inflammation of vestibular nerve.[10],[11],[12],[13] The vascular and the immune-mediated mechanism had been proposed in the past, but most of the recent research developments have supported the viral etiology.[9],[14],[15] The inflamed nerve gets entrapped inside bony internal auditory canal leading to the degeneration of nerve fibers. Understandably, the steroid therapy is supposed to be useful in the acute setting to reduce the inflammatory edema of the affected nerve. It has been shown that the use of systemic steroids early in the course of VN has resulted in better caloric response.[4],[16] However, the clinical recovery in terms of relief from the symptoms with steroid therapy was not different from that with the placebo.[16],[17] Nevertheless, the current treatment for VN includes the labyrinthine sedatives for symptomatic relief in the acute phase and the labyrinthine rehabilitation to promote the central vestibular compensation later on, without any definitive role of antiviral therapy.[18],[19],[20],[21],[22]

However, the persistence of episodic giddiness in nearly half of the affected patients contemplates further exploration of alternative treatment. Antiviral therapy seems promising in this regard since the reactivation of virus is the most probable cause of this recurrent giddiness in VN.[9] Optimistic anticipation about antiviral therapy in VN is also because of the fact that it has been able to provide additional benefit in Bell's palsy when given with steroids.[23],[24] VN is comparable to Bell's palsy in many pathophysiological characteristics and natural course.[25],[26] Moreover, the antiviral therapy has been helpful in similar viral-induced inflammatory conditions affecting other cranial nerves such as the facial nerve in Ramsay–Hunt syndrome,[27],[28] the cochlear nerve in sudden sensorineural hearing loss,[29] and the recurrent laryngeal nerve in bilateral abductor cord palsy.[30] This evidence-based review has critically analyzed the available literature, with the objective to determine if there is sufficient evidence to refute (or support) the antiviral therapy for VN.


  Materials and Methods Top


Search strategy

A detailed literature search was carried out by the author in the electronic databases which include PubMed, Scopus, Web of Science, IndMED, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane library. The terms “vestibular neuronitis” or “vestibular neuritis” or “acute vestibular dysfunction” or “vestibular nerve inflammation” or “acute peripheral vestibulopathy” or “episodic recurrent vertigo” or “vestibular neuropathy” AND “antiviral agents” or “antiviral therapy” or “acyclovir” or “ valacyclovir” or “therapy” or “treatment” were used for making the search in the above-mentioned databases. The references of the relevant publications were also looked upon with the intention of possible inclusion into the review. The overall study including the literature search, the scrutiny of articles, and the relevant reference's cross-check was carried out from July 2017 to October 2017.

Selection criteria

The predefined inclusion criteria for the selection of studies include “prospective randomized controlled trial (RCT) which compares the outcomes of any form of antiviral therapy in VN, with that of placebo or any form of steroid or any other alternative therapy.” The time of initiation of therapy and the duration of therapy were not included in the selection criteria; however, the follow-up data of more than 1-month duration was an important prerequisite for the inclusion of the study. The reported outcome measures were also not restricted during the selection of studies and any trials with any one or more of clinical recovery, caloric response, canal paresis rates, and time for recovery, as outcome measurement were deemed suitable for inclusion. No specific exclusion criteria were exercised during the selection of studies except for the language. Studies of any time period published in the English literature were to be included, provided they fulfill the inclusion criteria.

Selection of studies

Search in the above-mentioned electronic databases revealed a total of 581 publications. After meticulous screening, 517 articles were excluded as they were not relevant to the research question. Abstracts of the remaining 64 articles were carefully reviewed and only eight publications seemed to contain the necessary information. However, when full manuscripts of these eight articles were analyzed for study design and methodology, it was realized that only two primary interventional studies had contained the information regarding the use of antiviral agents in VN and only one of them was a prospective RCT [Figure 1]. A manual search of the databases using the references of the relevant articles on the VN and its therapy also did not reveal any additional study.
Figure 1: Selection of studies for the review

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  Results Top


Since only one RCT was available for inclusion into this review, detailed data extraction, segregation, and meaningful statistical analysis were not possible. However, as most of the current understanding and conclusions on antiviral therapy in VN come from this RCT, the methods and outcomes of the RCT have been briefly discussed underneath.

Strupp et al. have published this double-blinded RCT, in which, 141 patients of VN were randomized into four groups, to receive either of methylprednisolone, valacyclovir, placebo or both methylprednisolone and valacyclovir.[31] The drugs were administered within 3 days of the onset of symptoms, and the caloric response was measured once before intervention as well as after 1 year of intervention. A total of 114 patients completed the follow-up of 1 year and were included in the analysis. Although the caloric response had improved after 1 year in the group which received valacyclovir (n = 27), the improvement was not significantly different from the group which received placebo (n = 30). However, the groups which received methylprednisolone (n = 29) and methylprednisolone with valacyclovir (n = 28) had statistically significant improvement in caloric response, as compared to placebo group at 1 year. The cumulative effect of valacyclovir administration on canal paresis was found to be insignificant.


  Discussion Top


Although it is not wrong to infer that the valcyclovir does not improve caloric response in VN patients as per the RCT, there are certain issues one needs to consider before writing off the utility of antiviral therapy in VN. First, the reported outcomes in this RCT are not the appropriate parameters to decide upon the effectiveness of antiviral therapy. Many authors have independently confirmed that the improved caloric response does not necessarily imply symptomatic improvement in VN patients.[16],[17],[32] Authors of the RCT have neither reported the clinical course of the patients after antiviral therapy nor have collaborated the improved caloric response to individuals' symptomology. It would have been more meaningful had the authors commented about the clinical course in follow-up, in terms of “time for symptomatic improvement after therapy,” “presence or absence of episodic vertigo,” “duration between those episodes,” etc., Perhaps, these are the parameters which are likely to be benefited by antiviral therapy, considering the pathophysiology of VN.

In vitro studies have shown that the virus infects the vestibular ganglia in two forms – lytically and latently.[14] When acutely infected by the virus, lytic replication inside the ganglia causes inflammation and partial degeneration of fibers, leading to acute vertigo episode. However, as the immunity controls the viral replication, this infection persists latently without any symptoms. The latent infection can become the lytic replication again when the host's immunity is low, which corresponds to the reactivation of latent virus, manifesting clinically as recurrence of vertigo episode. It has also been shown that the addition of acyclovir suppresses the lytic replication in vitro.[14] These observations have certain clinical implications. The inhibition of lytic replication of the virus by acyclovir could potentially be used in VN, for controlling the recurrent episodes of vertigo by prescribing the antiviral agent. Such a supposition is supported by the report that the valacyclovir given for herpes labialis has completely relived the recurrent vertiginous episodes in a confirmed case of VN.[33] Another corroborative evidence for this extrapolation is the fact that the prolonged antiviral therapy completely controlled the vertigo episodes in 93 of 104 refractory cases of VN.[34] Interestingly, other than the RCT by Strupp et al., this is the only other primary interventional study published in the English literature, studying the effectiveness of antiviral therapy in VN.

In this prospective study by Gacek, either of acyclovir or valacyclovir was given to the nonresponding cases of VN (n = 104) after discontinuing all other previous medications and all the patients were followed up for a minimum of 8 years. Although most of these patients became free of vertigo within 2 weeks of initiating the antiviral therapy, they had to be kept under maintenance dose of antiviral agent for a longer duration for maintaining this symptom-free period. However, the authors have neither clarified the exact duration of the maintenance antiviral therapy nor have they commented about any side effects observed during this prolonged therapy. Considering that this study is an uncontrolled case series, it constitutes a lower level of evidence to formulate any recommendations based on its results. Nevertheless, the quantum of response shown in this study is not to be disregarded as “88% of refractory VN patients had no recurrence of symptoms with antiviral therapy, even at 8-year follow-up.”

There is a dearth in further research on this topic and unsurprisingly, most of the other publications/reviews related to VN have derived their conclusion on antiviral therapy based on the only RCT available on this topic, whose methodology seems inappropriate to answer the desired question. In other words, deeming the antiviral therapy as ineffective in VN seems inaccurate, since the available evidence is not sufficient for such a conclusion. The antiviral therapy has been beneficial in many other similar viral inflammatory conditions, and considering the recent concepts in the pathophysiology of VN, this therapy certainly seems to play a role in VN. The main drawback of the review is the inclusion of single study, precluding meaningful statistical analysis. However, by identifying this lack of trials on antiviral therapy in VN, this review hopes to form the epitope for further research in this particular area of antiviral therapy in VN. It is worthwhile to perform more randomized controlled studies with the appropriate dose and duration regimens of antiviral therapy the clinically sensible outcome measures along with the objective tests of canal response.


  Conclusions Top


There is only one RCT in English literature which has evaluated the effectiveness of antiviral therapy in VN. Although the results of this trial do not support antiviral therapy, the measured outcomes were not appropriate to evaluate the effectiveness of antiviral therapy. In view of the insufficient evidence to refute antiviral therapy and the recent understandings in the pathophysiology of VN, more RCTs with appropriate methodology are required to verify the role of antiviral agents in VN.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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