Following the first description in 1921, benign paroxysmal

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1 Original Research Otology and Neurotology Clinical Features of Recurrent or Persistent Benign Paroxysmal Positional Vertigo Otolaryngology Head and Neck Surgery 147(5) Ó American Academy of Otolaryngology Head and Neck Surgery Foundation 2012 Reprints and permission: sagepub.com/journalspermissions.nav DOI: / Seong Jun Choi, MD 1, Jong Bin Lee, MD 1, Hye Jin Lim, MD 2, Hun Yi Park, MD 2, Keehyun Park, MD, PhD 2, Seung Min In, MD 1, Jeong Hyun Oh, MD 1, and Yun-Hoon Choung, MD, DDS, PhD 2 No sponsorships or competing interests have been disclosed for this article. Abstract Objectives. To identify clinical features and causes of recurrent or persistent benign paroxysmal positional vertigo (BPPV) and to analyze the effectiveness of frequently repeated canalith repositioning procedures (CRPs). Study Design. Case series with chart review. Setting. Academic university hospital. Methods. The authors retrospectively reviewed the clinical records of 120 patients who were diagnosed with BPPV at the Dizziness Clinic in Ajou University Hospital, Korea, between 2004 and Persistent and recurrent BPPV were respectively defined as BPPV continuing more than 2 weeks and recurring BPPV in the same canals after at least 2 weeks of a symptom-free interval following previous successful treatments. The authors treated patients with frequently repeated CRPs such as the modified Epley maneuver or a barbecue rotation every 2 or 3 days in the outpatient clinic. Results. Among 120 patients with BPPV, 93 (77.5%) were typical, 15 (12.5%) were persistent, and 12 (10.0%) were recurrent. Although the most common cause was idiopathic in both recurrent and persistent BPPV, secondary causes, including trauma, were much more common in recurrent and persistent BPPV than in typical BPPV. Typical and recurrent BPPV developed most commonly in the posterior semicircular canals. Persistent BPPV was most commonly detected in the lateral semicircular canals. After frequently repeated CRPs, 91.7% and 86.7% of the patients with recurrent or persistent BPPV, respectively, had resolution of nystagmus and vertigo. Conclusion. Recurrent and persistent BPPV are not rare diseases and occur with a higher incidence than expected, especially in patients with secondary causes. However, they can be successfully treated with frequently repeated CRPs. Keywords benign paroxysmal positional vertigo, recurrence, treatment, diagnosis, canalith repositioning procedures Received January 25, 2012; revised May 8, 2012; accepted June 22, Following the first description in 1921, benign paroxysmal positional vertigo (BPPV) has been recognized as a common vestibular disorder it affects nearly 40% of patients with complaints of vertigo. 1 Benign paroxysmal positional vertigo has been postulated to be a result of the debris of degenerative otoconia floating freely in the semicircular canal (canalolithiasis) 2 or debris that becomes adherent to the cupula of the semicircular canal (cupulolithiasis). 3 Typical BPPV presents as an intermittent attack of vertigo over a brief period and torsional or horizontal nystagmus on provocative head motion. The most commonly involved canal in BPPV is the posterior semicircular canal (PSC); however, the horizontal semicircular canal (HSC) accounts for up to 40.5% of sites for BPPV. 4 For PSC-BPPV, physical therapy and canalith repositioning procedures (CRPs) were introduced to make vestibular habituation or move the free otolith to the utricle. 5-7 These maneuvers are very effective, up to 98%. 5-7 On the other hand, HSC-BPPV is considered more difficult to diagnose and treat than PSC-BPPV. However, this type of BPPV can be easily diagnosed with head-rolling tests and other tests and also can be successfully managed by CRPs such as barbecue rotation. 8,9 Thus, BPPV is generally considered a benign disease. However, some patients experience a serious disturbance with persistent or repeated attacks of BPPV even after several trials of CRPs. Nylen 10 was the first to recognize that some forms of positional nystagmus were not benign but were caused by central nervous system (CNS) diseases. Del 1 Department of Otorhinolaryngology, College of Medicine, Konyang University, Daejeon, Republic of Korea 2 Department of Otolaryngology, Ajou University School of Medicine, Suwon, Republic of Korea Corresponding Author: Yun-Hoon Choung, MD, DDS, PhD, Department of Otolaryngology, Ajou University School of Medicine, San 5, Wonchon-dong, Yeongtong-gu, Suwon , Republic of Korea yhc@ajou.ac.kr

2 920 Otolaryngology Head and Neck Surgery 147(5) Rio and Arriaga 11 reported that the lowest success rate with a single CRP was found in patients with prior labyrinthitis or trauma. Leveque et al 12 defined chronically disabling BPPV as refractory vertigo persistent for 1 year even with physical therapy. Many clinicians frequently see intractable BPPV with secondary or unknown causes that seriously affect patients normal activities, thus surgical solutions have been proposed for chronically disabled BPPV patients. 12 However, these surgical techniques are exceptional treatments and recently have been practiced with decreasing frequency because of surgical risk. Alternative treatments for recurrent or persistent BPPV are repeated CRPs, habituation therapy (Brandt-Daroff maneuver), 5 or automated nystagmus-based repositioning (Omniax system). 13 Therefore, we tried to classify patients with BPPV according to the time of clinical evolution and the recurrent pattern. Repeated CRPs with short intertreatment intervals, which are considered an easily applicable method, were used to treat recurrent or persistent BPPV. The purpose of this study was to identify clinical features and possible causes of recurrent or persistent benign BPPV and to analyze the effectiveness of repeated CRPs. Materials and Methods One hundred sixty-eight patients with BPPV who were diagnosed at the Dizziness Clinic in the Department of Otolaryngology, Ajou University Hospital, Suwon, Republic of Korea, between February 2004 and February 2008 were enrolled in this study. The study was approved by the Institutional Review Board of Ajou University School of Medicine, Suwon, Republic of Korea. The present study was limited to patients who directly visited our hospital without stopping at local clinics. Posterior semicircular canal BPPV was diagnosed with the Dix-Hallpike maneuver in the direction of the involved canal. Intense vertigo in conjunction with a burst of nystagmus with the typical characteristics of latency, crescendo, fatigability, and transience was considered necessary to establish the diagnosis, 1 with the nystagmus beating upward and toward the downside affected ear. 14 On the other hand, HC-BPPV was diagnosed by the presence of horizontal geotropic and apogeotropic paroxysmal nystagmus provoked by the head-rolling test, performed by turning the head from the supine to either lateral position. The geotropic type of horizontal nystagmus was denoted canalolithiasis of the lateral canal on the side with the more intense nystagmus, whereas the apogeotropic nystagmus was indicative of cupulolithiasis on the side with the less intense nystagmus. 14 Patients were excluded from the study if they had been treated with CRPs in local clinics, if involvement of CNS disorders had been identified by magnetic resonance imaging (MRI) or neurologic examination, if the diagnosis of multiple-canal BPPV was established on positional testing, if patients were diagnosed with acute vestibular neuritis, and if the follow-up period was less than 6 months. Eventually, 120 patients were enrolled, and their follow-up was 6 months at minimum. To enhance the confidence of the head roll test, Dix- Hallpike test, and results of CRPs, diagnosis and treatment of BPPV were performed by a tester who had a lot of clinical experience and knowledge of BPPV and has been working in the Dizziness Clinic more than 5 years. The tester recorded uncertain or refractory cases and had a discussion about that with the authors. We divided patients into 3 groups: typical, recurrent, and persistent BPPV. A typical BPPV was defined as a case that had a decrescendo course of characteristic vertigo, was easily controlled by CRPs within 2 weeks, and did not have recurrence during the follow-up period. A recurrent BPPV was defined as one with symptoms and nystagmus recurring in the same canal after at least 2 weeks of a symptom-free interval following previous successful treatments. A persistent BPPV meant a BPPV continuing for more than 2 weeks (more than 5 sessions) in the same canal despite repeated CRPs. All patients with BPPV were treated with frequently repeated CRPs. Frequently repeated CRP protocols were made up of 2 stages of maneuver and evaluation. We performed only 1 cycle of CRP on the first day of the treatment because of a relatively high resolution rate and patients fear on head motion. We treated patients with PSC-BPPV using modified Epley maneuvers. 6 Patients with the canalolithiasis (geotropic) type of HSC-BPPV were treated with 360 barbecue rotations in the direction of the nonaffected side from the affected eardown position. 15 The procedure consisted of moving the patient s head in step increments of 90, starting from supine in the direction of the healthy side until a 360 turn was accomplished. After every 90 step, the patient was asked to remain in the new position for 30 seconds. For the cupulolithiasis (apogeotropic) type of HSC-BPPV, vibrating attempts were first applied to the mastoid area of the affected ear for 10 seconds with an electric vibrator for the purpose of converting the apogeotropic type into the geotropic type. 15 Then we immediately performed 360 head rotation in the direction of the nonaffected side regardless of the nystagmus change. 15 After treatment, patients were given verbal instructions to avoid rapid head movements, extreme flexion and extension of the neck, and positions that provoke symptoms of vertigo for 2 to 3 days. The evaluation of treatment results was composed of the patient s symptoms and nystagmus by the Dix-Hallpike test and the head roll test. If the patient s symptoms or nystagmus did not disappear 2 days later, we made an effort to do CRP several times in a day until symptoms or nystagmus disappeared. All patients were followed up every 2 to 3 days. A negative positional response and improvement of symptoms verified that therapy for the BPPV was successful. We used electronystagmography (Micromedical Technologies, Inc, Chatham, Illinois) and a computerized video eye movement recorder (SLMED, Seoul, Korea) to document nystagmus. We did bithermal caloric tests (META-4; Micromedical Technologies, Inc) in some patients to evaluate canal paresis. The clinical charts of these patients were retrospectively reviewed with regard to sex ratio, incidence, causes, types

3 Choi et al 921 Figure 1. The incidence of persistent or recurrent benign paroxysmal positional vertigo. of involved semicircular canals, frequency of CRPs, and treatment results. Statistical analyses were done using SPSS statistical software version 18.0 (SPSS, Inc, an IBM Company, Chicago, Illinois). Chi-square tests with Bonferroni correction and analysis of variance (ANOVA) followed by post hoc Tukey test were used for comparison of clinical characteristics and CRPs of each group. The level of significance was set at P \.05. Exceptionally, a corrected P value \.05/3 was considered significant as a solution for the problem of multiple testing on the x 2 analysis. Results Incidence Of 120 patients with BPPV, 93 (77.5%) were typical, 15 (12.5%) persistent, and 12 (10.0%) recurrent (Figure 1). The mean (SD) ages of these groups were, respectively, 49.8 (12.2), 56.2 (9.8), and 47.8 (15.4) years. The sex ratio of men to women was 36:57 in the typical group, 3:12 in the persistent group, and 4:8 in the recurrent group. There were no significant differences in mean ages and sex ratios among the groups, but there were more women in all groups. The median periods of follow-up were 6.2 months (range, 6-12 months) in the typical group, 9.5 months (range, 6-31 months) in the persistent group, and 12.3 months (range, 6-29 months) in the recurrent group. Causes In typical BPPV, the causes were idiopathic (84.9%), trauma (8.6%), and sudden sensorineural hearing loss (3.2%). Idiopathic causes were also most common in recurrent and persistent BPPV. However, secondary causes were frequently found in recurrent or persistent BPPV. The most frequently detected causes were trauma (16.7%) and Ménière s disease (16.7%) in the recurrent type and trauma (13.3%) and sudden hearing loss (13.3%) in the persistent type (Table 1). Involved Canal Types Typical BPPV included 55 cases in PSCs and 38 cases in HSCs (24 canalolithiasis and 14 cupulolithiasis). For recurrent BPPV, 7 cases occurred in PSCs and 5 cases in HSCs (2 canalolithiasis, 3 cupulolithiasis). The persistent BPPV group consisted of 5 cases with PSC-BPPV and 10 cases with HSC-BPPV (3 canalolithiasis, 7 cupulolithiasis) (Figure 2). Typical or recurrent BPPV most commonly developed in PSCs. Persistent BPPV was most common in HSCs, especially in the type with cupulolithiasis. Response to Repeated CRPs After repeated CRPs, 91.7% with the recurrent type and 86.7% with persistent BPPV had resolution of the nystagmus and vertigo (Figure 3). For resolution of BPPV, trials of CRPs averaged sessions for the typical type, for the recurrent type, and for the persistent type of BPPV. Patients with persistent BPPV received a greater number of CRPs than did other types (P =.000). Analyzing the trial number of CRPs according to the possible causes, the average number of trials of CRPs were 3.3 sessions for sudden hearing loss, 2.0 for Ménière s disease, 1.7 for trauma, and 1.5 for idiopathic causes (Figure 4). Discussion Although BPPV is usually a self-limited disease or shows a high response to physical maneuvers, clinicians sometimes encounter atypical and intractable BPPV. Horii et al 16 defined intractable BPPV as cases showing either a persistent nystagmus or a frequent relapse of nystagmus that lasted more than a year after the initial diagnosis. They reported that the occurrence rate of intractable BPPV was 18 (3.6%) of the 495 patients. 16 Pérez et al 17 described that Table 1. Possible Causes of Persistent and Recurrent Benign Paroxysmal Positional Vertigo (N = 120) Possible Causes Typical Group (n = 93) Recurrent Group (n = 12) Persistent Group (n = 15) Idiopathic 79 (84.9) 8 (66.7) 11 (73.3) Trauma 8 (8.6) 2 (16.7) 2 (13.3) SSNHL 3 (3.2) 0 2 (13.3) Ménière s disease 2 (2.1) 2 (16.7) 0 Ear operations 1 (1.2) 0 0 Values are presented as No. (%). Abbreviation: SSNHL, sudden sensorineural hearing loss.

4 922 Otolaryngology Head and Neck Surgery 147(5) Figure 2. The kinds and types of semicircular canals involved in persistent or recurrent benign paroxysmal positional vertigo (BPPV). Figure 3. The resolution rate of canalith repositioning procedures in persistent or recurrent benign paroxysmal positional vertigo (BPPV). the recurrence rate of BPPV was 27% of the 69 patients. In our study, recurrent (12.5%) and persistent (10.0%) BPPV was not rare and presented with a higher incidence than we expected. The difference in incidence rate of intractable BPPV may be related to age or sex of the group, cause, the method of CRP, period of follow-up, and other undetermined reasons. Although the mechanism of persistent or recurrent BPPV is not established, hypotheses are intralabyrinthine fibrosis or ossification involving the endolymphatic space, 18 utricular macula lesions or lesions involving the membranous labyrinth, 19 cupula lithiasis, 20 endolymphatic hydrops, 21 otolith adherence to the membranous labyrinth, 22 vestibular atelectasia, 23 and so on. Schratzenstaller et al 24 reported evidence of filling defects in the semicircular canal seen on a labyrinth MRI for each of 5 patients who suffered from untreatable BPPV. From these hypotheses, persistent BPPV may be related to structural changes in membranous organs Figure 4. The trial frequency of canalith repositioning procedures in persistent or recurrent benign paroxysmal positional vertigo (BPPV). ANOVA, analysis of variance. or otolith adherence; recurrent BPPV may be caused by late detachment of the otolith from the cupula or membranous labyrinth. Benign paroxysmal positional vertigo is associated with various disorders of the labyrinth, including trauma, sudden hearing loss, acute vestibular neuronitis, Ménière s disease, ear surgeries, or, rarely, CNS disorders. However, most cases are thought to be idiopathic. 25,26 Smouha and Roussos 27 described 38 cases of intractable BPPV in which the causes were idiopathic (26%), traumatic (16%), otogenic (29%), and ischemia or CNS diseases (29%). Beynon et al 28 reported that the causes of the recurrent PSC-BPPV were idiopathic (84%) and a minor head injury (16%). In our study, the common causes of persistent BPPV were idiopathic (73.3%), trauma (13.3%), and sudden hearing loss (13.3%). For recurrent BPPV, the causes were idiopathic (66.7%), trauma (16.7%), or Ménière s disease (16.7%). In addition, problematic diseases in persistent and recurrent BPPV were found more frequently than that of typical BPPV, and more CRP repetitions were required to cure these patients. The results of this study grossly were very similar to the study by Beynon et al. 28 Furthermore, the patients with persistent BPPV had a high rate of sudden hearing loss in our study. The cause of cochlear damage in sudden sensorineural hearing loss (SSNHL) is viral infection, hypoperfusion, and so on. 29 Although most diagnoses are idiopathic for BPPV, labyrinth viral infections have been described in many reports. 30 Therefore, SSNHL can be associated with the occurrence of BPPV, and these coincidences represent wide labyrinthine damage. For this reason, more sessions of CRP are required as a treatment for patients who have SSNHL and BPPV at the same time. For some intractable BPPV, we should bear in mind that the cause of the BPPV might be a CNS disorder, and we frequently recommend an MRI check despite a low diagnostic yield. In this study, we also recommended brain or inner ear MRIs in recurrent or persistent BPPV but did not find CNS abnormalities.

5 Choi et al 923 In general, the most common type of BPPV is caused by the involvement of the PSC as this canal is most susceptible anatomically to the entrance of free-floating utricular particles during routine head motion, but HSC-BPPV accounts for approximately 10% to 40% of all patients presenting with BPPV. 4,31 In the present study, the incidence of HSC-BPPV was also about 40%, similar to that of the study by Chung et al. 4 The difference in incidence may be related to geographic, racial, and other undetermined reasons. However, it is not easy to find studies that describe the type of involved canals in recurrent and persistent BPPV. In our study, recurrent BPPV most commonly developed in PSCs (58.3%), but persistent BPPV was most frequently detected in HSCs, especially of the cupulolithiasis type (46.7%). The involved canal pattern of the persistent BPPV group was significantly different from that of the recurrent group. This finding might be caused by structural abnormalities of the canal, otolith sticky adherence to the cupula, or the absence of a standard method for position, duration, and strength of vibrations to detach the otolith from the cupula. Horii et al 16 hypothesized that intractable BPPV would be due to an otoconial jam in the canal or otoconial debris attached to the cupula. The stenosis and filling defect of the semicircular canals, observed in the inner ear MRI, would support this hypothesis. 16 Until now, many authors have been treating all patients with BPPV of the cupulolithiasis type with experience-based CRPs. Although the mechanism of persistent and recurrent BPPV remained unknown, we suggested that persistent BPPV might be related to structural changes in membranous organs or otolith adherence; recurrent BPPV might be caused by late detachment of the otolith from the cupula or membranous labyrinth. Further studies are needed to elucidate the mechanism of persistent and recurrent BPPV. From the involved canal s point of view, the mechanisms of recurrent or persistent BPPV look different. Studies show a wide range of response rates of BPPV, ranging from 44% to 100%. 28 Posterior semicircular canal BPPV has a good resolution rate of more than 90%, on average, after proper CRPs. 32 Although the success rate of managing HSC-BPPV was slightly lower than for PSC-BPPV, the success rate for HSC-BPPV was approximately 60% to 90%. 8 Although there were differences in success rates of various CRPs, BPPV is believed to be a benign disease that is easily treated by CRPs. In the present study, most of the patients with typical BPPV showed good improvement of symptoms after 1 or 2 sessions of CRP. Furthermore, considerable variability exists in terms of the number of times the CRP is applied for the initial treatment of BPPV. 33 Some authors perform only 1 CRP cycle at the initial treatment, whereas others repeat a fixed number of cycles or perform the CRPs repeatedly until the vertiginous symptoms extinguish or the Dix-Hallpike converts to negative. 34 Although it was not possible to determine the optimal number of cycles for the CRP or a protocol for repeated procedures, we thought the repeated application of the CRP was likely to be determined by the severity of the symptoms if they persist or a positive result of the Dix-Hallpike test or head roll test. Dorigueto et al 35 reported that aquatic physical therapy for vestibular rehabilitation (APVR) protocols was a very effective treatment for persistent BPPV. Norré and Beckers 36 insisted that the results of habituation exercises were similar to those achieved in the Semont maneuver after 6 weeks of follow-up. However, they did not report the rate of recurrence and persistence of BPPV in their patients. Many authors have tried many methods to increase the success rate of CRP, but up to the present time, there has been no formulated treatment method for persistent or recurrent BPPV. In the present study, frequently repeated CRP that was performed every 2 or 3 days was used for treatment of recurrent or persistent BPPV. Frequently repeated CRPs were effective for 91.7% of the recurrent type and 86.7% of persistent BPPV, although we needed several trials of CRPs to abolish positional nystagmus and the patient s symptoms. From this study, we recommend frequently repeated CRPs (every 2 or 3 days) as the primary treatment method of persistent or recurrent BPPV because of simplicity, lower cost, and ease of use in outpatient clinics. Conclusion Recurrent and persistent BPPV are not rare. They presented a higher incidence than expected, especially in patients with secondary causes, including trauma. However, they can be successfully treated with frequently repeated CRPs. Author Contributions Seong Jun Choi, drafting the manuscript, data analysis; Jong Bin Lee, data analysis, statistical analysis; Hye Jin Lim, data collection and analysis; Hun Yi Park, consult for study design; Keehyun Park, review of the manuscript; Seung Min In, acquisition of data; Jeong Hyun Oh, data collection; Yun-Hoon Choung, study design, result interpretation, correction of manuscript. Disclosures Competing interests: None. Sponsorships: None. Funding source: None. References 1. Dix R, Hallpike CS. The pathology symptomatology and diagnosis of certain common disorders of the vestibular system. Ann Otol Rhinol Laryngol. 1952;6: Hall SF, Ruby RRF, McClure JA. The mechanics of benign paroxysmal vertigo. J Otolaryngol. 1979;8: Schuknecht HF. Cupulolithiasis. 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