Introduction

Benign Paroxysmal Positional Vertigo (BPPV) is the most common type of vestibular disorder, characterized by episodic vertigo lasting for a few seconds induced by changes in the head posi-tion. The prognosis is good, with spontaneous recovery in approximately 20% of cases by one month and in up to 50 percent in three months [1]. Posterior semicircular canal (PSC) is the most common clinical variant, followed by horizontal and superior canals (HSC and SSC). Rarely BPPV may be bilateral, or affect more canals simultaneously [2-4]. Diagnosis is based on the charac-teristics of the nystagmus evoked by Dix Hallpike maneuver, used to explore the PSC and the SSC canals and Mc Clure maneuver or roll test for the HSC (Table 1). Treatment is based on different repositioning maneuvers, these are grounded on the two currently accepted etiopathogenic hypothesis, the cupulolithiasis and canalolithiasis theories5, both described by Schuknecht. The Epley (EM) and The Semont Maneuvers (SM) are for the posterior semi-circular canal; the Gufoni and Lempert maneuvers, for the horizontal semicircular canal; the Yacovino maneuver for the superior semicircular canal. The particle replacement maneuvers are very effective, especially in the case of the posterior duct: the success rate is estimated in 90 to 95% with an average of 1 to 3 maneuvers [3-8]. The rate is lower in the case of the HSC (85%) [9,10], the SCC success rate is dif-ficult to esti mate due to data scarcity. However, there are patients (3.5 to 12%, depending on the series) [11,12] in which the symptomatology and nystagmus persist despite the reiteration of the ma-neuvers, and others, where it recurs after the symptomatology has been resolved (around 25%, especially in the first 6 to 12 months). Horii et al [13] refers to these cases as intractable BPPV. In this scenario an imaging study by Magnetic Resonance Imaging (MRI) is mandatory to rule out inner ear or central nervous system abnormalities. Treatment of intractable BPPV is a challenge. Two surgical techniques have been described as the last therapeutic step after failure of reposi-tioning maneuvers: 1) the section of the posterior ampullary nerve and 2) the occlusion of the posterior semicircular canal. The latter is considered the most appropriate for patients with intrac-table vertigo, since is less destructive and easier to perform than the posterior ampullary nerve section [14]. Several endocrinological and metabolic factors have been proposed in relationship with persistent BPPV and intractable forms. Vitamin D, estrogens, growth hormone, thyroid hor-mones and corticosteroids seem to act in bone metabolism and otoconial mineralization [15]. Additionally corticosteroids after interacting with the intracellular glucocorticoid receptors of the inner ear, produce important anti-inflammatory effects and play a role in fluid and electrolyte regula-tion, improving homeostasis of the inner ear [16]. In several studies in which high resolution 3D MRI has been employed to study patients with intractable persistent BPPV, structural changes in the inner ear such as filling defects in the semicircular canals have been observed. These findings may indicate a narrowing of the semicircular canal suggesting an inflammatory process of the membranous labyrinth that could explain the failure of the repositioning maneuvers [17,18]. Based on these considerations, Perez et al [19] published in 2016 the first study on the use of intratympanic (IT) corticosteroids for the treatment of persistent BPPV of PSC in 9 patients. Authors showed that after 2 sessions of IT methylprednisolone injections, combined with repositioning maneu-vers, patients experienced symptoms improvement without recurrence in 78% of cases. Similar results have been reported by Kelkar et al [20] two years later using IT dexamethasone in two pa-tients. After reading these promising results, in 2017 we started treating intractable BPPV with IT dexamethasone injections combined with repositioning maneuvers. In this article we report our experience with four patients.

Table 1: Clinical characteristics according to the affected canal.

Materials and Methods

All patients diagnosed with BPPV between June 2017 and December 2019 in a tertiary universi-ty hospital and in two private hospitals were included and analyzed prospectively. A total of 72 patients were included. The high clinical suspicion based on the symptoms referred by the pa-tients was the key to diagnose the BPPV. In every case a complete otoneurological examination was performed, including otomicroscopy, tuning forks, audiometry if needed, exploration of spontaneous nystagmus, head thrust, Romberg and Unterberger tests. Dix Hallpike maneuver was employed to explore the PSC and SSC and roll test for the HSC. PSC, HSC and SSC were involved in 64, 5 and 3 patients respectively. EM and SM were used for the PSC, the Yacovino maneuver for the SSC and Lempert maneuver for the HSC. During the first encounter with the patient, nystagmus was observed with the naked eye. Patients that presented with a difficultto- explore nystagmus, doubts about its direction or poor response after one correctly executed ma-neuver, a videonystagmography was performed. According to the diagnostic protocol used in our department, all cases that required three or more maneuvers with complete resolution or not of the symptomatology, were studied with an MRI with gadolinium to rule out central causes of paroxysmal positional vertigo or inner ear abnormalities described in previous studies [21]. Patients that required six or more maneuvers were considered candidates for intratympanic injection of corticosteroids, as previously suggested by Perez et al [19]. In all cases a solution of 4mg/ ml dexa-methasone was infused into the middle ear in the affected side through a tympanostomy tube previously placed under microscope and local anesthesia. A 25-gauge spinal needle was em-ployed for this purpose. After each IT treatment, patients were told to avoid swallowing and to turn their head towards the non-affected side for 15 minutes (Figure 1). All patients initially had twoweekly injections of intratympanic dexamethasone, the intervals were increased progressively according to the symptoms and the vestibular examination. Before each dexamethasone injec-tion a DH maneuver was performed to confirm the persistence of BPPV, the following day a re-positioning maneuver was executed. Success was defined as the absence of symptoms and nystagmus during DH maneuver. Follow-up ranged from 15 to 23 months with a mean follow-up of 18.75 months [20].

Figure 1: The frequency of concomitant diseases in high- and low-risk groups.

Results

Four out of the 72 patients (5.5%) were included in the study three of them were female and one was a male (Table 2). The age at diagnosis ranged from 44 to 83 years old, with a mean age of 61.75 years. Posterior semicircular canal was involved in all cases and no specific cause was identified in any of them. One case showed multicanal involvement of posterior and superior right semicircular canals. No bilateral involvement was observed. A gadolinium MRI was per-formed in all patients, no central nervous system or inner ear abnormalities were detected. One of the patients had a previous diagnosis of multiple sclerosis shown in the MRI. After six unsuc-cessful repositioning maneuvers, treatment with IT dexamethasone was conducted. A grommet was placed in the affected ear (3 in the right side and 1 in the left side) under local anesthesia in the outpatient clinic and IT dexamethasone was administered. Three patients experienced symptom resolution. Two, four and five IT injections were needed respectively. One patient experienced subjective clinical improvement, but nystagmus and vertigo persisted during DH maneuver after 8 IT dexamethasone injections. No complications or side effects were observed during treatment and none of the 3 cured patients experienced disease recurrence during the follow up period [21].

Table 2: Patients Treated with dexamethasone IT injections.

Discussion

BPPV is a common cause of vertigo. Most cases are idiopathic and respond successfully to canalicular repositioning maneuvers, others are self-limited and require no intervention [22]. A smaller group of patients experience persistent symptoms that don’t resolve after multiple repositioning maneuvers (persistent vertigo), or recur after the symptomatology has been resolved (recurrent vertigo). The pathological bases remain unclear although several risk factors have been considered. All patients that belong to either of these two groups should be assessed with a neuro-radiological study to rule out central nervous system conditions that can mimic a BPPV before considering other factors. Although a specific cause is rarely identified, age and female sex seem to be intimately related with the origin of BPPV since it is more commonly observed in female patients older than 60 years old. In a large series of patients with BPPV published by the authors, 6.25% of patients were considered refractory to the treatment, the presence of previous otoneuro-logic disorders such as vestibular neuritis and multiple canal involvement were strongly associat-ed with a higher risk of refractory BPPV [21]. Similar results were observed by Babac et al [23]. Age related vestibular degeneration and hormonal factors involved in changes in bone metabolism could play a role in the etiopathogenesis of BPPV [24,25] and could explain some of the refractory cases. Different studies have identified osteoporosis/ osteopenia, estrogen deficiency, and low serum levels of vitamin D as potential risk factors for BPPV and higher risk of recurrence [26]. On the other hand, the possibility of multiple canal involvement in 4 to 21% of cases in different series [27] and the fact that recurrent vertigo can affect any of the three canals in both labyrinths, suggest that some patients with BPPV do not suffer from a specific ailment in one of their inner ears, but rather develop a pathological condition involving their vestibular organs28. It is likely that a chronic inflammatory process of the inner ear or an alteration of the calcium sodium home-stasis of the labyrinth may be responsible for the refractory cases of BPPV. This hypothesis is suggested also by several findings observed in various studies where a threedimensional high-resolution MRI has been employed to study the inner ear of patients with refractory vertigo13. In these cases a higher incidence of abnormal MRI images (stenosis and canal filling defects) than normal controls have been reported. These anomalies might actually correspond to a ductal narrowness or to plugs of otoconial debris¹³ that could be related to an inflammatory process or anomaly of calcium metabolism. It has been shown that glucocorticoid receptors are widely distributed throughout the inner ear, comprising the vestibular structures including the utricular macula, saccule and semicircular canal duct epithelium. Considering the potential role of gluco-corticoids receptors in the inner ear, IT injections of steroids could improve intractable vertigo through two possible pathways 1) anti-inflammatory properties and 2) modulation of the calcium metabolism. Based on these observations, Pérez et al. began to treat patients with intractable BPPV with intratympanic methylprednisolone and published their encouraging results in 2016. Steroids are largely employed to treat a great variety of inner ear disorders, such as Ménière’s disease, autoimmune hearing loss and sudden idiopathic sensorineural hearing loss. IT steroid administration is a common procedure in the ENT outpatient clinic, it is usually well tolerated by the patient with a very low rate of complications. In our experience we have observed a higher treatment tolerance to the administration of dexamethasone than methylprednisolone, subsequently the first one was given to all patients. The decision to place a tympanostomy tube under microscope was based on the advantages of avoiding multiple punctures and being able to administer the drug with minor disturbance of the patient. In 3 out of 4 patients the symptomatology disappeared and showed no signs of recurrence throughout the followingup period. One patient showed no signs of improvement after multiple IT injections. In this case we identified a multiple canal involvement, a well described risk factor in the literature for persistent/recurrent BPPV [28]. Our results support the ones previously reported by Pérez et al in 2016 and by Kelkar et al two years later.

Conclusion

The use of IT steroids to treat patients with BPPV refractory to the maneuvers showed encouraging results in 3 out of 4 patients, with control of symptoms and improvement on quality of life during the follow-up. Although this study has several limitations, authors consider it is relevant to perform a multicenter randomized clinical trial to assess the efficacy of intratympanic steroids in the management of refractory BPPV.

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