Review of the pathology underlying benign paroxysmal positional vertigo
Article Information
Received: September 05, 2019; Accepted: November 13, 2019
Sertac Yetiser, Department of Otolaryngology–Head and Neck Surgery, Anadolu Medical Center, Cumhuriyet Mahallesi, 2255 sokak, No. 3, Gebze, Kocaeli 41400, Turkey. Email: sertac.yetiser@anadolusaglik.org
The pathophysiological mechanism underlying benign paroxysmal positional vertigo (BPPV) is related to free-floating debris/otoliths in the semicircular canal (canalolithiasis) or debris/otoliths attached to the cupula (cupulolithiasis). These debris/otoliths are considered to originally accumulate after detachment from the neuroepithelium of the utricular macula secondary to a type of degeneration. An idiopathic form, which is assumed to occur spontaneously, is diagnosed when the causative pathology is obscure. However, an association between various other systemic or inner ear conditions and BPPV has been reported, indicating the existence of secondary BPPV. This study was performed to present the first review of the pathology underlying BPPV following a complete PubMed/Medline search. In total, 1932 articles published from 1975 to 2018 were reviewed. The articles were classified according to 17 potentially causative factors (aging; migraine; Meniere's disease; infection; trauma; idiopathic sudden sensorineural hearing loss; sleeping habits; osteoporosis and vitamin D insufficiency; hyperglycemia and diabetes mellitus; chronic head and neck pain; vestibule or semicircular canal pathology; pigmentation disorders; estrogen deficiency; neurological disorders; autoimmune, inflammatory, or rheumatologic disorders; familial or genetic predisposition; and allergy). A discussion of the underlying cause of BPPV for each factor is presented.
Benign paroxysmal positional vertigo (BPPV) can be defined as transient, position-induced torsional, vertical, or horizontal nystagmus with vertigo. Symptoms are provoked in association with a specific head position. The diagnosis is supported by the brief latency, limited duration, fatigability, and reversibility of the nystagmus upon returning to an erect position. The pathology is based on displacement of the cupula due to either free-floating debris/otoliths in the semicircular canal (canalolithiasis) or attachment of debris/otoliths to the cupula (cupulolithiasis).
Any inner ear pathology that detaches the otoconia appears to be capable of causing BPPV. Secondary BPPV is diagnosed when an associated cause is clearly identified. However, the underlying pathology is often obscure; in such cases, idiopathic BPPV is diagnosed.1 This study was performed to review the pathologies possibly underlying the occurrence of BPPV.
A review of the literature on the pathology underlying BPPV was conducted. The articles were identified by means of a search of the PubMed database using the keyword "BPPV," which yielded 1932 articles. The search included articles published from 1975 to 2018. In total, 545 articles were reviewed for the study after exclusion of those that were not published in English, those that were technical or guideline reports, those based on the outcomes of a specific treatment method or analysis of quality of life only, experimental studies that focused on a mathematical model of BPPV, and single case reports. Comparative studies were excluded if the discussion of the underlying pathology was not clear. If more than one article by the same author(s) or institution was found, only the most recent article matching the aforementioned criteria and those that were not overlapping were included.
Seventeen factors possibly associated with the pathology underlying BPPV were identified: aging; migraine; Meniere's disease; trauma; infection and vestibular neuronitis; idiopathic sudden sensorineural hearing loss; sleeping habits; osteoporosis and vitamin D insufficiency; hyperglycemia and diabetes mellitus; chronic head and neck pain; vestibule or semicircular canal pathology; pigmentation disorders; estrogen deficiency; neurological disorders; autoimmune, inflammatory, or rheumatologic disorders; familial or genetic predisposition; and allergy.
After searching articles regarding BPPV in older people, including reports focused on the aging of the labyrinth, 78 articles were selected. Forty-seven articles were about the association of migraine and BPPV; 56 were about Meniere's disease and BPPV; 37 were about viral infections and vestibular neuronitis, which may have a role in the pathogenesis of BPPV; 63 were about BPPV following trauma; 25 were about idiopathic sudden sensorineural hearing loss accompanying BPPV; 21 were about the role of sleeping habits in BPPV; 41 investigated the relationship among vitamin D levels, osteoporosis, and BPPV; 15 focused on the association among hyperglycemia, diabetes mellitus, and BPPV; 8 were about the relationship among myalgia, fibromyalgia, chronic neck pain, and BPPV; 18 investigated vascular or anatomical abnormalities, including a large vestibular aqueduct, Arnold-Chiari malformation, abnormalities in the vertebral and basilar arteries, hypoplasia of the semicircular canals, and other conditions that may have a role in the pathogenesis of BPPV; 2 were about the relationship between BPPV and pigmentation disorders; 5 were about estrogen deficiency in BPPV; 9 focused on the association of BPPV and neurological disease, including multiple sclerosis and Parkinson disease; 12 were about possible defects associated with autoimmunity in patients with BPPV; and 4 were about the familial incidence and possible genetic role in the pathogenesis of BPPV. No article addressed the association between BPPV and allergy. The distribution of these articles about the pathogenesis of BPPV is shown in Figure 1.
Figure 1. Distribution of articles focusing on the pathogenesis of BPPV. BPPV, benign paroxysmal positional vertigo; MD, Meniere's disease; VN, vestibular neuronitis; ISSHL, idiopathic sudden sensorineural hearing loss; Vit D, vitamin D deficiency; PD, pigmentation disorder; ND, neurological disorder.
Aging
Aging is a risk factor for utricular dysfunction in idiopathic BPPV.2 Animal studies have indicated the occurrence of otoconial degeneration with aging.3,4 The incidence of BPPV is higher at advanced ages, and it has been rarely reported to occur in children. Picciotti et al.5 reviewed 475 patients with BPPV and found that comorbidities were present in 72.6% of patients with recurrent BPPV, and this incidence was higher in female and older patients. Yetiser and Ince6 reviewed the age distribution of 263 patients from 10 to 84 years of age and found that 5 patients were younger than 20 years. Bachor et al.3 reviewed 186 temporal bones from 121 individuals between the ages of newborn and 10 years. They found that the incidence of basophilic cupular deposits, which have been clinically implicated in BPPV, was 12.7%. The lower occurrence in children than adults suggested that the accumulation of deposits could be due to aging of the vestibular labyrinth. The average age at onset of the first episode of BPPV is >50 years. Residual symptoms such as dizziness and balance disorders are more common after otolith repositioning in older patients, and the recurrence rate is high.2,4 This is probably because of otoconia fragmentation secondary to aging. Notably, however, this process is multifactorial.
Migraine
Previous studies have shown that patients with migraine seem more likely to develop BPPV than subjects in the control group.7–9 Kim et al.10 performed a nationwide cohort study and reported a higher incidence of BPPV in patients with migraine (6.0%) than in control subjects (3.2%). Faralli et al.11 reviewed the recovery time, residual dizziness, and recurrence in patients with BPPV with and without migraine. The authors found no significant difference in the number of maneuvers needed to achieve recovery., and they stated that a direct pathophysiological link between migraine and BPPV is unlikely.11 Yetiser and Gokmen12 analyzed whether clinical features in patients with BPPV and migraine differ from those in patients with BPPV without migraine. The comparative analysis of the cure rate of the therapeutic maneuvers between the two groups showed no significant differences.
Meniere's disease
Several reports have indicated an association between Meniere's disease and BPPV. The incidence greatly varies from 0.5% to 44.0%.1,13–15 Meniere's disease and BPPV may share common pathological ground because of the high incidence of Meniere's disease and BPPV in the same ear.16–18 Hydropically induced damage to the maculae of the utricle and saccule or partial obstruction of the membranous labyrinth are possible mechanisms underlying the coexistence of Meniere's disease and BPPV.19–21 Several studies have shown that when BPPV is associated with Meniere's disease, more therapeutic sessions are needed and the recurrence rate is high.16,17,22,23
Infection and vestibular neuronitis
Viral infections may play a role in the pathogenesis of BPPV. The occurrence of BPPV following vestibular neuronitis is not rare.24,25 Hanci et al.26 reported higher serological values for herpesvirus, Epstein–Barr virus, adenovirus, and cytomegalovirus in patients with BPPV than in the control group. BPPV secondary to vestibular neuronitis is associated with a lower age at onset, more frequent involvement of the posterior canal, greater presence of canal weakness, and higher rate of recurrence.27 Arbusow et al.28 isolated herpes simplex virus in the labyrinth of 48% of studied temporal bones. However, the occurrence of infection-related otoconial detachment needs histopathological confirmation in animal studies.
Trauma
Trauma is a common cause of BPPV. Pisani et al.29 reviewed 3060 patients with a clinical diagnosis of BPPV, and a clear association with a traumatic event was present in 23.4% of patients. Chang et al.30 reviewed 768 patients with BPPV and found that 9.2% of patients with BPPV had undergone previous dental surgery. Gordon et al.31 followed the training program of 63 American football players and reported 16 additional cases of BPPV during follow-up. The most common types of trauma were motor vehicle crashes, common falls, temporal bone or stapes surgery, and head trauma.32–35 Acoustic or electrical stimulation, pressure, intense physical activity, and mechanical trauma can lead to otoconial dislodgement.36–38 Traumatic BPPV may involve multiple canals and requires repeated maneuvers.32,39–41
Idiopathic sudden sensorineural hearing loss
Idiopathic sudden sensorineural hearing loss may accompany BPPV. The incidence of BPPV among patients with sudden hearing loss ranges from 5.4% to 12.1%.42–44 Karlberg et al.45 reported four cases of sudden hearing loss and ipsilateral posterior canal BPPV, all of which were resolved following a repositioning maneuver. The findings indicated that the pathology was located inside the labyrinth rather than within the cochleovestibular nerve. Based on these cases, the authors proposed viral labyrinthitis rather than a vascular infarct. Conversely, El-Saied et al.46 described five patients with hearing loss and BPPV and proposed a vascular insult as the common pathophysiological mechanism.46 It seems that when BPPV is associated with sudden hearing loss, treatment requires several sessions of a repositioning maneuver.43,44 Lee and Ban47 reviewed 38 patients with sudden hearing loss and BPPV and proposed that the association of these two pathologies represents definite vestibular damage and is closely related to a poor prognosis.
Sleeping habits
Gyo48 was one of the first to indicate the occurrence of BPPV in a group of patients following bedrest restrictions after unrelated surgeries. Sleeping habits may be closely associated with the affected side in patients with BPPV. The ear affected by BPPV has been found to be consistent with the head-lying side.49,50 Sato et al.51 and Shim et al.52 reported that otoconial debris dislodged from the utricle under the influence of gravity may fall into the lateral or posterior semicircular canals of the undermost ear during sleep. This is seen particularly more often in patients with posterior canal BPPV when the affected ear is down.53 The recurrence rate is high when the patient continues to sleep on the affected side.54 Sleeping habits may therefore be associated with hearing loss. Patients with profound unilateral hearing loss often lie on the ear with hearing loss while sleeping to keep the better-hearing ear open to the environment.
Osteoporosis and vitamin D insufficiency
Research on the relationship between vitamin D levels and BPPV is evolving. Otoconia consist of calcium carbonate crystals, which are connected to saccular and utricular hair cells with protein fibers. Vitamin D receptors regulate transportation of calcium through epithelial channels.55 Therefore, vitamin D deficiency may affect the otoconia structure and integrity. The prevalence of a decreased bone mass density among people with BPPV is 81%.56 A low serum vitamin D level is a risk factor for BPPV.57 Yamanaka et al.58 found that the rate of recurrence of BPPV in patients with osteoporosis was significantly higher than that in patients with normal bone mineral density (56.3% vs. 16.1%, respectively). When the symptom severity and recurrence rate were compared between patients with BPPV who had vitamin D deficiency versus a normal serum vitamin level, patients with vitamin D deficiency were found to have more severe symptoms with a longer duration, a lower success rate of repositioning maneuvers, and a higher recurrence rate.59,60 The vitamin D level is particularly low in postmenopausal women with BPPV.61 A low vitamin D level is associated with osteoporosis, and medication to treat osteoporosis can provide protection against BPPV and reduce the incidence of recurrence.62,63 Talaat et al.64 reported that the rate of recurrence of BPPV in patients with an elevated serum vitamin D level following replacement therapy was quite low during the follow-up period (4%) when compared with that in patients with a low serum vitamin D level (43%).
Hyperglycemia and diabetes mellitus
Disruption of capillary vessels causes microvascular degeneration leading to proximal and distal peripheral sensory and motor neuropathy in patients with chronic hyperglycemia and hyperinsulinemia. Yoda et al.65 reviewed 28 temporal bones from 14 patients with type 1 diabetes mellitus and 56 normal temporal bones from 28 age-matched individuals. The prevalence of cupular and free-floating deposits in the lateral and posterior semicircular canals was significantly higher in the patients with type 1 diabetes mellitus than in the patients with normal temporal bones, and this difference was associated with the duration of disease rather than with aging.65 D'Silva et al.66 reported that BPPV was seen 46% of patients with type 2 diabetes mellitus compared with 37% of individuals without diabetes mellitus, and the 42% association between type 2 diabetes mellitus and BPPV was mediated by hypertension. Hyperglycemia is also a risk factor for recurrence.67
Chronic head and neck pain
Observational studies have indicated a connection between chronic BPPV and headache and neck pain.68 Patients with pain benefit from otolith repositioning maneuvers.69 Whether myalgia, fibromyalgia, and pain influence detachment of otoconia remains unclear because most such studies are observational and the results are based on self-scoring questionnaires. Whether neck pain is the cause or consequence of BPPV also remains unclear.
Vestibule or semicircular canal pathology
BPPV is usually a self-limiting disease that responds well to repositioning maneuvers. Schratzenstaller et al.70 reviewed the magnetic resonance images of patients with atypical and intractable BPPV. They found structural changes such as fractures or filling defects in the semicircular canals. Magnetic resonance imaging is helpful to understand micro-abnormalities of the semicircular canals in patients with persistent symptoms.71 In contrast, no gross anatomical abnormalities were found in that study.70 Recurrent BPPV is reportedly related to volumetric abnormalities of the vestibular aqueduct.72 The incidence of BPPV in patients with a large vestibular aqueduct is approximately 19%.73 However, no evidence-based pathological mechanism was demonstrated.
Pigmentation disorders (vitiligo)
Melanocytes arise from the neural crest and are found in the utricle, saccule, ampulla, and endolymphatic duct and sac. Impaired proliferation of these cells results with white patches of the skin known as vitiligo.74 The role and presence of pigment cells in the inner ear are subject to investigation. Melanocytes are particularly present around capillary walls. They seem to have a vasomotor function and play a role in metabolite exchanges.75 Vitiligo-associated auditory problems may be related to a degenerative process.76 Dawoud et al.77 reviewed 30 patients with vitiligo and reported that 17% had BPPV. However, it is difficult to conclude that pigmentation disorders are a cause of BPPV because of the lack of sufficient data.
Estrogen deficiency
The prevalence of BPPV greatly increases with age in both sexes. However, menopausal women are especially susceptible. Decreases in estrogen and progesterone levels can cause inner ear microcirculation disorders in postmenopausal women.78 Animal studies have indicated that estrogen receptors are important in otoconia maintenance. Bilateral ovariectomized mice have reduced expression of otoconial components. The density of otoconia decreases but the size of otoconia increases in female ovariectomized rats. Eventually, ectopic debris formation in the ampulla increases under estrogen deficiency.79,80
Neurological disorders
BPPV has been reported in patients with multiple sclerosis and Parkinson's disease.81,82 The association between BPPV and neurological disorders is weak, and data on the pathophysiological mechanism connecting these two clinical disorders are lacking.83 The occurrence of BPPV in patients with neurological disease seems to be coincidental.
Autoimmune, inflammatory, or rheumatologic disorders
Possible defects associated with autoimmunity in patients with BPPV have been a topic of interest. However, conflicting results have been reported. The association of giant cell arteritis and BPPV has been reported in 20% of patients, suggesting an ischemic pattern of otoconia degeneration.84 Goto et al.85 reviewed reactive oxygen metabolites and circulating soluble vascular cell adhesion molecule to investigate the possible contributory role of angiitis to the onset of BPPV. The results were significant, suggesting alternative pharmacological treatment. Pérez et al.86 reported successful intratympanic methylprednisolone treatment in seven of nine patients with persistent posterior canal BPPV. Amor-Dorado et al.87 found that the incidence of BPPV among 59 patients with ankylosing spondylitis was low (10%). Modugno et al.88 found anti-thyroid antibodies in 27% of patients with BPPV and proposed the existence of immune complex-mediated inner ear disease. However, another study showed no significant difference in the level of thyroid-stimulating hormone, anti-thyroid peroxidase antibody, or anti-thyroglobulin antibody between patients with and without BPPV.89
Familial incidence
Gizzi et al.90 reviewed the family histories of patients with BPPV, and the results suggested a genetic predisposition to utricular otoconia dislodgement. The authors compared the familial tendencies between 120 successive patients with BPPV and 120 successive patients with dizziness. Patients with BPPV were five times more likely to have relatives with BPPV than were patients with dizziness (control group). However, no clear hereditary or environmental influence on the development of BPPV was found. Whether BPPV is inherited in an autosomal dominant fashion needs to be confirmed in further studies.91
Allergy
No research focusing on the association between BPPV and allergy is available.
This review has provided a discussion of some possible underlying causes of BPPV, although the idiopathic form is clearly the most common. Lee at al.92 reviewed 718 patients with BPPV. Sixty-nine patients (9.6%) had inner ear disorders associated with BPPV, and the most common pathologies were sudden hearing loss, Meniere's disease, and vestibular neuronitis.92 Further studies are required to explore clear links before presenting solid statements. Otoconial degeneration due to aging seems to be important. However, BPPV cannot be solely explained by aging. Secondary problems should be investigated before initiating the clinical decision-making process in patients with BPPV. The gravitational impact of the sleeping position is an interesting factor. Patients should be recommended to sleep on the healthy side following repositioning maneuvers; this is a minor but valuable precaution to reduce recurrence. Additionally, vitamin D and estrogen deficiency should be considered when treating postmenopausal women with BPPV. BPPV following trauma is usually clear in cases of surgery, head trauma, or vehicle accidents. Patients should also be questioned regarding minor impacts. BPPV occurs in combination with many pathologic conditions. The present review has indicated that aging, trauma, migraine, Meniere's disease, and vestibular neuronitis are the most frequently investigated topics. However, studies of vitamin D deficiency have recently been increasing.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Sertac Yetiser https://orcid.org/0000-0003-1430-1026
| 1. | Karlberg, M, Hall, K, Quickert, Net al. What inner ear diseases cause benign paroxysmal positional vertigo? Acta Otolaryngol 2000; 120: 380–385. Google Scholar | Crossref | Medline | ISI |
| 2. | Fujimoto, C, Kawahara, T, Kinoshita, Met al. Aging is a risk factor for utricular dysfunction in idiopathic benign paroxysmal positional vertigo. Front Neurol 2018; 9: 1049. doi: 10.3389/fneur.2018.01049. Google Scholar | Crossref | Medline |
| 3. | Bachor, E, Wright, CG, Karmody, CS. The incidence and distribution of cupular deposits in the pediatric vestibular labyrinth. Laryngoscope 2002; 112: 147–151. Google Scholar | Crossref | Medline | ISI |
| 4. | Jang, YS, Hwang, CH, Shin, JYet al. Age-related changes on the morphology of the otoconia. Laryngoscope 2006; 116: 996–1001. Google Scholar | Crossref | Medline |
| 5. | Picciotti, PM, Lucidi, D, De Corso, Eet al. Comorbidities and recurrence of benign paroxysmal positional vertigo: personal experience. Int J Audiol 2016; 55: 279–284. Google Scholar | Crossref | Medline |
| 6. | Yetiser, S, Ince, D. Demographic analysis of benign paroxysmal positional vertigo as a common public health problem. Ann Med Health Sci Res 2015; 5: 50–53. Google Scholar | Crossref | Medline |
| 7. | Teixido, M, Baker, A, Isildak, H. Migraine and benign paroxysmal positional vertigo: a single-institution review. J Laryngol Otol 2017; 131: 508–513. Google Scholar | Crossref | Medline |
| 8. | Uneri, A. Migraine and benign paroxysmal positional vertigo: an outcome study of 476 patients. Ear Nose Throat J 2004; 83: 814–815. Google Scholar | SAGE Journals |
| 9. | Chu, CH, Liu, CJ, Lin, LYet al. Migraine is associated with an increased risk for benign paroxysmal positional vertigo: a nationwide population-based study. J Headache Pain 2015; 16: 62. Google Scholar | Crossref | Medline |
| 10. | Kim, SK, Hong, SM, Park, ISet al. Association between migraine and benign paroxysmal positional vertigo among adults in South Korea. JAMA Otolaryngol Head Neck Surg 2019; 145: 307–312. Google Scholar | Crossref | Medline |
| 11. | Faralli, M, Cipriani, L, Del Zompo, MRet al. Benign paroxysmal positional vertigo and migraine: analysis of 186 cases. B-ENT 2014; 10: 133–139. Google Scholar | Medline |
| 12. | Yetiser, S, Gokmen, MH. Clinical aspects of benign paroxysmal positional vertigo associated with migraine. Int Tinnitus J 2015; 19: 64–68. Google Scholar | Crossref | Medline |
| 13. | Proctor, LR. Results of serial vestibular testing in unilateral Meniere's disease. Am J Otol 2000; 21: 552–558. Google Scholar | Medline |
| 14. | van Esch, BF, van Benthem, PP, van der Zaag-Loonen, HJet al. Two common second causes of dizziness in patients with Meniere's disease. Otol Neurotol 2016; 37: 1620–1624. Google Scholar | Crossref | Medline |
| 15. | Taura, A, Funabiki, K, Ohgita, Het al. One-third of vertiginous episodes during the follow-up period are caused by benign paroxysmal positional vertigo in patients with Meniere's disease. Acta Otolaryngol 2014; 134: 1140–1145. Google Scholar | Crossref | Medline |
| 16. | Yetişer, S. Co-existence of benign paroxysmal positional vertigo and Meniere's Syndrome. J Int Adv Otol 2017; 13: 65–68. Google Scholar | Crossref | Medline |
| 17. | Kutlubaev, MA, Xu, Y, Hornibrook, J. Benign paroxysmal positional vertigo in Meniere's disease: systematic review and meta-analysis of frequency and clinical characteristics. J Neurol. Epub ahead of print 13 August 2019. DOI: 10.1007/s00415-019-09502-x. Google Scholar |
| 18. | Luryi, AL, Lawrence, J, Bojrab, Det al. Patient, disease, and outcome characteristics of benign paroxysmal positional vertigo with and without Meniere's disease. Acta Otolaryngol 2018; 138: 893–897. Google Scholar | Crossref | Medline |
| 19. | Jahn, AF. Benign positional vertigo and endolymphatic hydrops: what is the connection? J Laryngol Otol 2017; 131: 658–660. Google Scholar | Crossref | Medline |
| 20. | Hornibrook, J, Bird, P. A new theory for Meniere's disease: detached saccular otoconia. Otolaryngol Head Neck Surg 2017; 156: 350–352. Google Scholar | SAGE Journals | ISI |
| 21. | Gross, EM, Ress, BD, Viirre, ESet al. Intractable benign paroxysmal positional vertigo in patients with Meniere's disease. Laryngoscope 2000; 110: 655–659. Google Scholar | Crossref | Medline | ISI |
| 22. | Balatsouras, DG, Ganelis, P, Aspris, Aet al. Benign paroxysmal positional vertigo associated with Meniere's disease: epidemiological, pathophysiologic, clinical, and therapeutic aspects. Ann Otol Rhinol Laryngol 2012; 121: 682–688. Google Scholar | SAGE Journals | ISI |
| 23. | Zhu, M, Yu, F, Zhou, Fet al. Benign paroxysmal positional vertigo associated with Meniere's disease. J Vestib Res 2018; 28: 359–364. Google Scholar | Crossref | Medline |
| 24. | Zapala, DA, Shapiro, SA, Lundy, LBet al. Simultaneous acute superior nerve neurolabyrinthitis and benign paroxysmal positional vertigo. J Am Acad Audiol 2006; 17: 481–486. Google Scholar | Crossref | Medline |
| 25. | Mandalà, M, Santoro, GP, Awrey, Jet al. Vestibular neuritis: recurrence and incidence of secondary benign paroxysmal positional vertigo. Acta Otolaryngol 2010; 130: 565–567. Google Scholar | Crossref | Medline |
| 26. | Hanci, D, Ulusoy, S, Muluk, NBet al. Do viral infections have a role in benign paroxysmal positional vertigo? B-ENT 2015; 11: 211–218. Google Scholar | Medline |
| 27. | Balatsouras, DG, Koukoutsis, G, Ganelis, Pet al. Benign paroxysmal positional vertigo secondary to vestibular neuritis. Eur Arch Otorhinolaryngol 2014; 271: 919–924. Google Scholar | Crossref | Medline | ISI |
| 28. | Arbusow, V, Theil, D, Strupp, Met al. HSV-1 not only in human vestibular ganglia but also in the vestibular labyrinth. Audiol Neurootol 2001; 6: 259–262. Google Scholar | Crossref | Medline | ISI |
| 29. | Pisani, V, Mazzone, S, Di Mauro, Ret al. A survey of the nature of trauma of post-traumatic benign paroxysmal positional vertigo. Int J Audiol 2015; 54: 329–333. Google Scholar | Crossref | Medline |
| 30. | Chang, TP, Lin, YW, Sung, PYet al. Benign paroxysmal positional vertigo after dental procedures: a population-based case-control study. PLoS One 2016; 11: e0153092. Google Scholar | Crossref | Medline |
| 31. | Gordon, CR, Levite, R, Joffe, Vet al. Is posttraumatic benign paroxysmal positional vertigo different from the idiopathic form? Arch Neurol 2004; 61: 1590–1593. Google Scholar | Crossref | Medline |
| 32. | Park, SK, Kim, SY, Han, KHet al. Benign paroxysmal positional vertigo after surgical drilling of the temporal bone. Otol Neurotol 2013; 34: 1448–1455. Google Scholar | Crossref | Medline |
| 33. | Suarez, H, Alonso, R, Arocena, Met al. Clinical characteristics of positional vertigo after mild head trauma. Acta Otolaryngol 2011; 131: 377–381. Google Scholar | Crossref | Medline | ISI |
| 34. | Magliulo, G, Gagliardi, M, Cuiuli, Get al. Stapedotomy and post-operative benign paroxysmal positional vertigo. J Vestib Res 2005; 15: 169–172. Google Scholar | Medline |
| 35. | Di Girolamo, S, Fetoni, AR, Di Nardo, Wet al. An unusual complication of cochlear implant: benign paroxysmal positional vertigo. J Laryngol Otol 1999; 113: 922–923. Google Scholar | Crossref | Medline | ISI |
| 36. | Dan-Goor, E, Eden, JC, Wilson, SJet al. Benign paroxysmal positional vertigo after decompression sickness: a first case report and review of the literature. Am J Otolaryngol 2010; 31: 476–478. Google Scholar | Crossref | Medline |
| 37. | Giacomini, PG, Ferraro, S, Di Girolamo, Set al. Benign paroxysmal positional vertigo after intense physical activity: a report of nine cases. Eur Arch Otorhinolaryngol 2009; 266: 1831–1835. Google Scholar | Crossref | Medline |
| 38. | Chen, G, Li, Y, Si, Jet al. Treatment and recurrence of traumatic versus idiopathic benign paroxysmal positional vertigo: a meta-analysis. Acta Otolaryngol 2019; 139: 727–733. Google Scholar | Crossref | Medline |
| 39. | Aron, M, Lea, J, Nakku, Det al. Symptom resolution rates of posttraumatic versus nontraumatic Benign paroxysmal positional vertigo: a systematic review. Otolaryngol Head Neck Surg 2015; 153: 721–730. Google Scholar | SAGE Journals | ISI |
| 40. | Gökler, O, Koçak, İ, Aydoğan, Eet al. Evaluation of Benign paroxysmal positional vertigo in American football players. J Int Adv Otol 2018; 14: 295–298. Google Scholar | Crossref | Medline |
| 41. | Ahn, SK, Jeon, SY, Kim, JPet al. Clinical characteristics and treatment of benign paroxysmal positional vertigo after traumatic brain injury. J Trauma 2011; 70: 442–446. Google Scholar | Crossref | Medline |
| 42. | Hong, SM, Yeo, SG. Clinical analysis of patients with idiopathic sudden sensorineural hearing loss and benign paroxysmal positional vertigo. Acta Otolaryngol 2013; 133: 439–442. Google Scholar | Crossref | Medline |
| 43. | Kim, MB, Ban, JH. Benign paroxysmal positional vertigo accompanied by sudden sensorineural hearing loss: a comparative study with idiopathic benign paroxysmal vertigo. Laryngoscope 2012; 122: 2832–2836. Google Scholar | Crossref | Medline |
| 44. | Lee, JB, Choi, SJ. Canal paresis in Benign paroxysmal positional vertigo secondary to sudden sensorineural hearing loss. Otol Neurotol 2015; 36: 1708–1713. Google Scholar | Crossref | Medline |
| 45. | Karlberg, M, Halmagyi, GM, Büttner, Uet al. Sudden unilateral hearing loss with simultaneous ipsilateral posterior semicircular canal benign paroxysmal positional vertigo: a variant of vestibulo-cochlear neurolabyrinthitis? Arch Otolaryngol Head Neck Surg 2000; 126: 1024–1029. Google Scholar | Crossref | Medline |
| 46. | El-Saied, S, Joshua, BZ, Segal, Net al. Sudden hearing loss with simultaneous posterior semicircular canal BPPV: possible etiology and clinical implications. Am J Otolaryngol 2014; 35: 180–185. Google Scholar | Crossref | Medline |
| 47. | Lee, NH, Ban, JH. Is BPPV a prognostic factor in idiopathic sudden sensory hearing loss? Clin Exp Otorhinolaryngol 2010; 3: 199–202. Google Scholar | Crossref | Medline |
| 48. | Gyo, K. Benign paroxysmal positional vertigo as a complication of postoperative bedrest. Laryngoscope 1988; 98: 332–333. Google Scholar | Crossref | Medline | ISI |
| 49. | Cakir, BO, Ercan, I, Cakir, ZAet al. Relationship between the affected ear in benign paroxysmal positional vertigo and habitual head-lying side during bedrest. J Laryngol Otol 2006; 120: 534–536. Google Scholar | Crossref | Medline |
| 50. | Korres, SG, Papadakis, CE, Riga, MGet al. Sleep position and laterality of benign paroxysmal positional vertigo. J Laryngol Otol 2008; 122: 1295–1298. Google Scholar | Crossref | Medline |
| 51. | Sato, G, Sekine, K, Matsuda, Ket al. Effects of sleep position on time course in remission of positional vertigo in patients with benign paroxysmal positional vertigo. Acta Otolaryngol 2012; 132: 614–617. Google Scholar | Crossref | Medline |
| 52. | Shim, DB, Kim, JH, Park, KCet al. Correlation between the head-lying side during sleep and the affected side by benign paroxysmal positional vertigo involving the posterior or horizontal semicircular canal. Laryngoscope 2012; 122: 873–876. Google Scholar | Crossref | Medline |
| 53. | Shigeno, K, Ogita, H, Funabiki, K. Benign paroxysmal positional vertigo and head position during sleep. J Vestib Res 2012; 22: 197–203. Google Scholar | Crossref | Medline |
| 54. | Lopez-Escámez, JA, Gámiz, MJ, Fiñana, MGet al. Position in bed is associated with left or right location in benign paroxysmal positional vertigo of the posterior semicircular canal. Am J Otolaryngol 2002; 23: 263–266. Google Scholar | Crossref | Medline |
| 55. | Lundberg, YW, Zhao, X, Yamoah, EN. Assembly of the otoconia complex to the macular sensory epithelium of the vestibule. Brain Res 2006; 1091: 47–57. Google Scholar | Crossref | Medline |
| 56. | Parham, K, Leonard, G, Feinn, RSet al. Prospective clinical investigation of the relationship between idiopathic benign paroxysmal positional vertigo and bone turnover: a pilot study. Laryngoscope 2013; 123: 2834–2839. Google Scholar | Crossref | Medline | ISI |
| 57. | Jeong, SH, Kim, JS, Shin, JWet al. Decreased serum vitamin D in idiopathic benign paroxysmal positional vertigo. J Neurol 2013; 260: 832–838. Google Scholar | Crossref | Medline |
| 58. | Yamanaka, T, Shirota, S, Sawai, Yet al. Osteoporosis as a risk factor for the recurrence of benign paroxysmal positional vertigo. Laryngoscope 2013; 123: 2813–2816. Google Scholar | Crossref | Medline |
| 59. | Jang, YS, Kang, MK. Relationship between bone mineral density and clinical features in women with idiopathic benign paroxysmal positional vertigo. Otol Neurotol 2009; 30: 95–100. Google Scholar | Crossref | Medline |
| 60. | Kahraman, SS, Ozcan, O, Arli, Cet al. Calcium homeostasis during attack and remission in patients with idiopathic benign paroxysmal positional vertigo. Otol Neurotol 2016; 37: 1388–1392. Google Scholar | Crossref | Medline |
| 61. | Han, W, Fan, Z, Zhou, Met al. Low 25-hydroxyvitamin D levels in postmenopausal female patients with benign paroxysmal positional vertigo. Acta Otolaryngol 2018; 138: 443–446. Google Scholar | Crossref | Medline |
| 62. | Vibert, D, Kompis, M, Häusler, R. Benign paroxysmal positional vertigo in older women may be related to osteoporosis and osteopenia. Ann Otol Rhinol Laryngol 2003; 112: 885–889. Google Scholar | SAGE Journals | ISI |
| 63. | Mikulec, AA, Kowalczyk, KA, Pfitzinger, MEet al. Negative association between treated osteoporosis and benign paroxysmal positional vertigo in women. J Laryngol Otol 2010; 124: 374–376. Google Scholar | Crossref | Medline |
| 64. | Talaat, HS, Kabel, AM, Khaliel, LHet al. Reduction of recurrence rate of benign paroxysmal positional vertigo by treatment of severe vitamin D deficiency. Auris Nasus Larynx 2016; 43: 237–241. Google Scholar | Crossref | Medline |
| 65. | Yoda, S, Cureoglu, S, Yildirim-Baylan, Met al. Association between type 1 diabetes mellitus and deposits in the semicircular canals. Otolaryngol Head Neck Surg 2011; 145: 458–462. Google Scholar | SAGE Journals | ISI |
| 66. | D'Silva, LJ, Staecker, H, Lin, Jet al. Retrospective data suggests that the higher prevalence of benign paroxysmal positional vertigo in individuals with type 2 diabetes is mediated by hypertension. J Vestib Res 2016; 25: 233–239. Google Scholar | Crossref | Medline |
| 67. | Webster, G, Sens, PM, Salmito, MCet al. Hyperinsulinemia and hyperglycemia: risk factors for recurrence of benign paroxysmal positional vertigo. Braz J Otorhinolaryngol 2015; 81: 347–351. Google Scholar | Crossref | Medline |
| 68. | Molvaer, OI. Chronic Benign paroxysmal positional vertigo (BPPV): A possible cause of chronic, otherwise unexplained neck-pain, headache, and widespread pain and fatigue, which may respond positively to repeated particle repositioning maneuvers (PRM). Scand J Pain 2017; 4: 231–232. Google Scholar | Crossref |
| 69. | Iglebekk, W, Tjell, C, Borenstein, P. Treatment of chronic canalithiasis can be beneficial for patients with vertigo/dizziness and chronic musculoskeletal pain, including whiplash related pain. Scand J Pain 2017; 8: 1–7. Google Scholar | Crossref |
| 70. | Schratzenstaller, B, Wagner-Manslau, C, Alexiou, Cet al. High-resolution three-dimensional magnetic resonance imaging of the vestibular labyrinth in patients with atypical and intractable benign positional vertigo. ORL J Otorhinolaryngol Relat Spec 2001; 63: 165–177. Google Scholar | Crossref | Medline | ISI |
| 71. | Dallan, I, Bruschini, L, Neri, Eet al. The role of high-resolution magnetic resonance in atypical and intractable benign paroxysmal positional vertigo: our preliminary experience. ORL J Otorhinolaryngol Relat Spec 2007; 69: 212–217. Google Scholar | Crossref | Medline |
| 72. | Manzari, L. Enlarged vestibular aqueduct (EVA) related with recurrent benign paroxysmal positional vertigo (BPPV). Med Hypotheses 2008; 70: 61–65. Google Scholar | Crossref | Medline | ISI |
| 73. | Song, JJ, Hong, SK, Kim, JSet al. Enlarged vestibular aqueduct may precipitate benign paroxysmal positional vertigo in children. Acta Otolaryngol 2012; 132: S109–S117. Google Scholar | Crossref | Medline |
| 74. | Moellmann, G, Klein-Angerer, S, Scollay, DAet al. Extracellular granular material and degeneration of keratinocytes in the normally pigmented epidermis of patients with vitiligo. J Invest Dermatol 1982; 79: 321–330. Google Scholar | Crossref | Medline | ISI |
| 75. | Gill, SS, Salt, AN. Quantitative differences in endolymphatic calcium and endocochlear potential between pigmented and albino guinea pigs. Hear Res 1997; 113: 191–197. Google Scholar | Crossref | Medline |
| 76. | Aydogan, K, Turan, OF, Onart, S. Audiological abnormalities in patients with vitiligo. Clin Exp Dermatol 2006; 31: 110–113. Google Scholar | Crossref | Medline | ISI |
| 77. | Dawoud, EAE, Ismail, EI, Eltoukhy, SAet al. Assessment of auditory and vestibular functions in vitiligo patients. J Otol 2017; 12: 143–149. Google Scholar | Crossref | Medline |
| 78. | Yang, L, Xu, Y, Zhang, Yet al. Mechanism underlying the effects of estrogen deficiency on otoconia. J Assoc Res Otolaryngol 2018; 19: 353–362. Google Scholar | Crossref | Medline |
| 79. | Vibert, D, Sans, A, Kompis, Met al. Ultrastructural changes in otoconia of osteoporotic rats. Audiol Neurootol 2008; 13: 293–301. Google Scholar | Crossref | Medline | ISI |
| 80. | Yang, CJ, Kim, Y, Lee, HSet al. Bone mineral density and serum 25-hydroxyvitamin D in patients with idiopathic benign paroxysmal positional vertigo. J Vestib Res 2018; 27: 287–294. Google Scholar | Crossref | Medline |
| 81. | Frohman, EM, Kramer, PD, Dewey, RBet al. Benign paroxysmal positioning vertigo in multiple sclerosis: diagnosis, pathophysiology and therapeutic techniques. Mult Scler 2003; 9: 250–255. Google Scholar | SAGE Journals | ISI |
| 82. | Aranke, SV, Sethi, KD. Benign paroxysmal positional vertigo in Parkinson's disease. Neurology 2003; 61: 1156. Google Scholar | Crossref | Medline |
| 83. | van Wensen, E, van Leeuwen, RB, van der Zaag-Loonen, HJet al. Benign paroxysmal positional vertigo in Parkinson's disease. Parkinsonism Relat Disord 2013; 19: 1110–1112. Google Scholar | Crossref | Medline |
| 84. | Amor-Dorado, JC, Llorca, J, Costa-Ribas, Cet al. Giant cell arteritis: a new association with benign paroxysmal positional vertigo. Laryngoscope 2004; 114: 1420–1425. Google Scholar | Crossref | Medline | ISI |
| 85. | Goto, F, Hayashi, K, Kunihiro, Tet al. The possible contribution of angiitis to the onset of benign paroxysmal positional vertigo (BPPV). Int Tinnitus J 2010; 16: 25–28. Google Scholar | Medline |
| 86. | Pérez, P, Franco, V, Oliva, Met al. A pilot study using intratympanic methylprednisolone for treatment of persistent posterior canal benign paroxysmal positional vertigo. J Int Adv Otol 2016; 12: 321–325. Google Scholar | Crossref | Medline |
| 87. | Amor-Dorado, JC, Barreira-Fernández, MP, Vázquez-Rodríguez, TRet al. Benign paroxysmal positional vertigo and clinical test of sensory interaction and balance in ankylosing spondylitis. Otol Neurotol 2011; 32: 278–283. Google Scholar | Crossref | Medline |
| 88. | Modugno, GC, Pirodda, A, Ferri, GGet al. A relationship between autoimmune thyroiditis and benign paroxysmal positional vertigo? Med Hypotheses 2000; 54: 614–615. Google Scholar | Crossref | Medline |
| 89. | Sari, K, Yildirim, T, Borekci, Het al. The relationship between benign paroxysmal positional vertigo and thyroid autoimmunity. Acta Otolaryngol 2015; 135: 754–757. Google Scholar | Crossref | Medline |
| 90. | Gizzi, M, Ayyagari, S, Khattar, V. The familial incidence of benign paroxysmal positional vertigo. Acta Otolaryngol 1998; 118: 774–777. Google Scholar | Crossref | Medline | ISI |
| 91. | Gizzi, MS, Peddareddygari, LR, Grewal, RP. A familial form of benign paroxysmal positional vertigo maps to chromosome 15. Int J Neurosci 2015; 125: 593–596. Google Scholar | Crossref | Medline |
| 92. | Lee, NH, Ban, JH, Lee, KCet al. Benign paroxysmal positional vertigo secondary to inner ear disease. Otolaryngol Head Neck Surg 2010; 143: 413–417. Google Scholar | SAGE Journals | ISI |
