|Year : 2018 | Volume
| Issue : 1 | Page : 47-52
Audio-vestibular dysfunction in rheumatoid arthritis: An undervalued extra-articular feature
Reem Elbeltagy1, Dalia Galhom1, Marwa Hammad2, Ghada A Dawa2
1 ENT Department, Audio-Vestibular Medicine, Faculty of Medicine, Zagazig University, Zagazig, El Sharkia, Egypt
2 Department of Rheumatology and Rehabilitation, Faculty of Medicine, Zagazig University, Zagazig, El Sharkia, Egypt
|Date of Web Publication||24-May-2018|
Dr. Reem Elbeltagy
ENT Department of Audio.Vestibular Medicine, Faculty of Medicine, Zagazig University, Zagazig, El Sharkia
Source of Support: None, Conflict of Interest: None
Objective: The study objective was to assess vestibular system either peripherally or centrally in patients with rheumatoid arthritis (RA) using video-nystagmography (VNG) and cervical vestibular-evoked myogenic potentials (cVEMP) in an Egyptian group of RA patients and to study whether there is a correlation between hearing levels, VNG, and cVEMP test results. Materials and Methods: This study was a comparative cross-sectional study. A total of forty individuals (twenty apparently healthy controls [40 ears] and twenty RA patients previously diagnosed by a rheumatologist [40 ears]) were included in the study. RA patients were recruited from the Rheumatology and Internal Medicine Departments of Zagazig University Hospitals. All participants gave their written consent before participation in the study. All participants in the study were subjected to basic audiological evaluation and vestibular evaluation (cVEMP-VNG). Results: There was a highly significant difference in VEMP latencies between RA patients and controls (P < 0.001) and nonsignificant difference as regards amplitude (P > 0.05). There was no statistically significant difference in VEMP latencies and amplitude between males and females of the study group (P > 0.05). There was a nonsignificant difference between VEMP latencies and amplitudes among subgroups A and B. All RA patients showed absence of spontaneous gaze-evoked positional and positioning nystagmus, normal oculomotor test, and unilateral caloric weakness in 12 ears. Conclusion: The findings of the current study add more evidence to the cochlea–vestibular involvement in patients with RA. Audio-vestibular function assessment is highly recommended for all RA patients as a routine examination.
Keywords: Cervical vestibular-evoked myogenic potential, rheumatoid arthritis, video-nystagmography
|How to cite this article:|
Elbeltagy R, Galhom D, Hammad M, Dawa GA. Audio-vestibular dysfunction in rheumatoid arthritis: An undervalued extra-articular feature. Indian J Otol 2018;24:47-52
|How to cite this URL:|
Elbeltagy R, Galhom D, Hammad M, Dawa GA. Audio-vestibular dysfunction in rheumatoid arthritis: An undervalued extra-articular feature. Indian J Otol [serial online] 2018 [cited 2021 Apr 11];24:47-52. Available from: https://www.indianjotol.org/text.asp?2018/24/1/47/233127
| Introduction|| |
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease of unknown etiology that affects approximately 1% of the worldwide population. Females are more commonly affected than males, usually between 30 and 50 years of age. The hallmark feature of RA is the presence of chronic symmetric polyarthritis of the hands and feet.
Although RA primarily targets the synovial membranes, it does not exclusively affect the joints., Extra-articular affection is also noted including rheumatoid nodules and ophthalmologic, cardiopulmonary, renal, and neurologic diseases. Moreover, Felty's syndrome, secondary vasculitis, and amyloidosis may also occur. Eighty percent of RA patients are “seropositive,” having a positive rheumatoid factor (RF), while about 20% are “seronegative.” Seropositivity and long disease duration are determinants of extra-articular involvement in RA patients.
Hearing impairment is a common problem in the general population. The association between hearing impairment and autoimmune disease was first described by McCabe in 1979. The probability of auditory system involvement in RA has been one of the areas with great interest; however, the results of previous studies evaluating the link between RA and hearing impairment are really confusing. Huang et al. in 2018 demonstrated that RA patients are at an increased risk of developing hearing loss (HL) and recommended scheduled auditory examinations for prevention and early detection. RA is thought to affect the auditory system through different mechanisms causing different types of HL.,,, Severe hearing impairment is significantly associated with having a hearing-related disability and self-reported communication difficulties. Social and psychological well-being in those patients may be profoundly affected. Extra-articular manifestations and complications of disease including the auditory system may all be attenuated or reduced with effective treatment.
Few studies have assessed the relationship between RA and vestibular function.,, Other studies denied it such as the studies reported by Kakani et al. and King et al. did not find vestibular system dysfunction in patients with RA.,,
The aim of this study was to assess vestibular system either peripherally or centrally in patients with RA using video-nystagmography (VNG) and cervical vestibular-evoked myogenic potentials (cVEMP) in an Egyptian group of RA patients and to study whether there is a correlation between hearing levels, VNG, and cVEMP test results.
| Materials and Methods|| |
Study design and subjects
This study was a comparative case–control study. A total of forty individuals (twenty apparently healthy controls [40 ears] and twenty RA patients previously diagnosed by a rheumatologist [40 ears]) were included in the study. RA patients were recruited from the Rheumatology and Internal Medicine Departments of Zagazig University Hospitals. All participants gave their written consent before participation in the study. The institutional review board approval for this work was obtained on 2017.
- Inclusion criteria included patients that fulfilled the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism Classification (EULAR) criteria for Rheumatoid Arthritis  and age above 16 years
- Exclusion criteria included age above 55 years, family history of HL, history of occupational noise exposure, history of ototoxic drug intake (other than treatment for RA), recent history or presence of any otological problem (such as ear discharge, earache, and ear surgery), systemic diseases such as diabetes mellitus, hypertension, or thyroid dysfunction), or any neurological symptoms.
According to the hearing thresholds, the study group was divided into four subgroups as follows:
- Subgroup A: Ears with normal hearing sensitivity
- Subgroup B: Ears with high-frequency sensorineural HL
- Subgroup C: Ears with normal caloric test
- Subgroup D: Ears with caloric weakness.
The new 2010 ACR/EULAR Rheumatoid Arthritis classification criteria by Aletaha et al. 2010, overruled the “old” ACR criteria of 1987 in clinical practice and are adapted for early RA diagnosis. The new classification criteria, published by the ACR and the EULAR, provide a point value between 0 and 10. Four areas are covered in the diagnosis as follows: joint involvement, serological factors (RF and anti-cyclic citrullinated peptide), acute-phase reactants (erythrocyte sedimentation rate and C-reactive protein), and duration of arthritis. However, a score of 6 or greater classifies a person with a diagnosis of RA.
Full history taking included personal history, history of HL, tinnitus, discharge, earache, headache or vertigo, past history of systemic disease, physical trauma, ototoxic drug or previous operations, and family history.
This included examination of preauricular region, ear pinna, postauricular region, external acoustic canal, and tympanic membrane.
Basic audiological evaluation
Basic audiological evaluation included the following:
- Pure-tone audiometry using Orbiter 922 (GM Otomtrix, Denmark): This included air conduction (air conduction hearing thresholds were determined by frequency range between 0.250 and 8 kHz) and bone conduction (bone conduction hearing thresholds were determined by frequency range between 0.500 and 4 kHz). Hearing thresholds >25 dB were considered as HL
- Speech audiometry (speech reception threshold using Arabic spondee words and the word discrimination scores using Arabic phonetically balanced words)
- Immittancemetry using Amplaid 724 (Amplifon, Italy). This included tympanometry and acoustic reflex threshold measurement.
- cVEMP using intelligent hearing system-evoked potential (GN Otometrics - ICS Chartr EP 200, Copenhagen, Denmark). The stimuli were broadband click with rarefaction polarity, 100-μs duration, and 125 sweeps with repetition rate of 5 click/s. The recorded potentials were filtered through a band-pass filter of 30–1500 Hz, with analysis time of 50 ms and at an intensity of 95 dBnHL. Electrode montage: surface electrodes were placed on midpoints of each sternomastoid muscle – one for the right side and then to the left side, with a reference electrode on ipsilateral upper sternum. A ground electrode was placed on the forehead. At least two consecutive averages were recorded from each side to verify reproducibility. The average of two runs was taken for the amplitude and latencies. For latency, the peak latencies of p1 and n1 were measured. p1 is the first positive peak of VEMP and n1 is the first negative peak following p1. The latency was defined as the time from the onset of the stimulus to the first positive peak. For evaluation of the amplitude, the positive-negative peak (p1-n1) was measured. The peak-to-peak amplitude was measured from the maximum positive deflection to the following maximum deflection
- VNG was performed using VNG Incident Command System Chart 200. The following tests were performed:
- Oculomotor tests
- Smooth pursuit testing: The patients were instructed to watch a target that moves horizontally in a sinusoidal fashion at a low frequency (0.2–0.7 Hz) with position amplitude of 200 in each direction. The computer then calculated the gain of smooth pursuit. A gain of <70% indicated impairment
- Saccade testing: The patients were instructed to fixate with eye movements while keeping the head stationary series of randomly displayed dots or lights at eccentricities of 5–300, both to the right and left. Observe for saccades: latency, velocity, accuracy, conjugacy, and asymmetry. Latency of >280° ms, accuracy of <80%, and peak velocity of <300° were considered abnormal. The patient with prolonged latency was diagnosed as having impaired saccadic movement if at least one of the accuracy or peak velocity scores was also outside the reference range
- Optokinetic nystagmus: It measures jerk nystagmus created by presenting a horizontally moving visual field to the patient, at velocities of 30, 40, or 600/s, for ~1 min, followed by a 1-min rest, after which the pattern was presented in the opposite direction.
Positional tests: The eye movements of each patient were recorded for 30 s without visual fixation. The patient had been placed in the sitting, supine, right ear down, left ear down, right side, left side, and head hanging positionsPositioning test (Dix–Hallpike test): each patient was seated upright on the examination table and head is turned 45° such that the chin is toward the right shoulder. The patients were rapidly lowered with the head supported into the right head hanging position 30° below the horizontal position. The patient remains in this position for at least 30 s with careful observation for nystagmus or vertigo (Frenzel lenses will aid in the identification of nystagmus). The patient returned to the upright position and the maneuver was repeated with the head turned 450° toward the left shoulderWater caloric tests: Bi-thermal caloric tests were performed; each ear was irrigated with water at temperatures of 30°C and 44°C for 40 s. The recordings of responses were conducted for 3 min. Canal paresis and directional preponderance were calculated according to Jongkees' formula. Values >20% for canal paresis and 25% for directional preponderance were considered abnormal.
Analysis of data was done by IBM computer using Statistical Package for the Social Sciences, version 20 (SPSS Inc., Chicago, Illinois, USA), software as follows: description of quantitative variables as mean, standard deviation (SD) and qualitative variables as number and percentage. t-test was used for parametric data to compare quantitative variables (standard deviation <50% mean). Pearson's correlation test was used to rank different variables either in positive or inverse manner. Chi-square test was used for finding relations between nonparametric data. P > 0.05 was considered statistically insignificant, P < 0.05 was considered statistically significant, and P < 0.001 was considered highly statistically significant.
| Results|| |
Demographic data and disease duration
Ages ranged between 16 and 55 years, with a mean age of 35 years (±9 years). There were 14 females (60%) and 6 males (40%). Half of the RA patients had disease duration ranging from 5 to 10 years [Table 1].
Pure tone thresholds in rheumatoid arthritis patients
[Table 2] shows the means of pure tone thresholds in dB in RA patients subdivided into subgroups A and B. Subgroup A shows normal hearing sensitivity and subgroup B shows high-frequency sensorineural HL.
Effect of age, sex, and duration of hearing loss on hearing sensitivity, vestibular-evoked myogenic potentials, and caloric testing in patients with rheumatoid arthritis
Age, sex, and duration of HL had no effect on hearing sensitivity, VEMP, and caloric testing in RA patients (P > 0.05) as shown in [Table 3], [Table 4], [Table 5].
|Table 3: The effect of age, sex, and duration of hearing loss on hearing sensitivity|
Click here to view
|Table 4: Comparison between subgroup C and subgroup D regarding age and duration of hearing loss|
Click here to view
|Table 5: The correlation of age and duration of hearing loss with latency and amplitude of vestibular-evoked myogenic potentials|
Click here to view
Comparison between vestibular-evoked myogenic potential wave latencies and amplitudes among patients and controls, males and females, and among subgroups
As shown in [Table 6] and [Table 7], there was a highly significant difference in VEMP latencies between patients and controls (P < 0.001) and nonsignificant difference as regards amplitude (P > 0.05). There was no statistically significant difference in VEMP latencies and amplitude between males and females of the study group (P > 0.05). There was a nonsignificant difference between VEMP latencies and amplitudes among subgroups A and B.
|Table 6: Comparison between vestibular-evoked myogenic potential wave latencies and amplitudes among patients, controls, males, and females|
Click here to view
|Table 7: Comparison between vestibular-evoked myogenic potential latencies and amplitudes among different subgroups|
Click here to view
Video-nystagmography in patients with rheumatoid arthritis
All RA patients showed absence of spontaneous gaze-evoked positional and positioning nystagmus, normal oculomotor test, and unilateral caloric weakness in 12 ears [Table 8].
| Discussion|| |
RA is considered one of the autoimmune disorders that affect ears, causing reversible sensorineural HL. The autoimmune sensorineural HL (SNHL) is usually bilateral, fluctuant, and may be associated with vestibular manifestations. The aim of our study was to assess central and peripheral vestibular affection in RA patients and its relation with hearing levels, VNG, and VEMP results.
In the present study, 13 patients (65%) had high-frequency SNHL and 6 patients had normal hearing sensitivity. These results matched with that of previous studies that suggest the association between RA and SNHL., Furthermore, El-Fatta et al. reported that about 57.75% of patients with RA had SNHL. Similar result was reported by Oztürk et al. (19%), where they found that the percentage of association varied from 24% to 60%. However, these results were different from the results found by Halligan et al., where they did not find any difference in objective audiometric assessments in patients with RA when compared with non-RA controls.
In this study, 65% of patients had SNHL and no patients complained of conductive HL (CHL), this agreed with the results found by Heyworth and Liyanage  who suggested that there was no evidence that suggests hearing impairment due to rheumatoid involvement of the ossicular joints. Furthermore, Dikici et al. reported that the conductive component may start later after the occurrence of sensorineural component that will result in mixed HL. On the other hand, El-Fatta et al. reported only five (11.11%) cases with CHL. In addition, Murdin et al. reported that CHL is also present in patients with RA, but at a lower prevalence, between 0% and 13%.
SNHL may be a result of vasculitis that causes auditory neuropathy which is a part of mononeuritis multiplex, and also may be a result of the autoimmune process that causes destruction of cochlear hair cell. Moreover, salicylate and nonsteroidal anti-inflammatory drugs that used in treatment of RA could have an ototoxic effect on cochlear hair cell.,,,,
In this study, latencies of p13 and n23 were significantly higher in RA patients than controls. This agreed with the results reported by Heydari et al. Moreover, this could be attributed to slow conduction along the vestibulospinal pathway that may occur in RA patients and lead to elimination of VEMP response or increased latency.
On the other hand, there was insignificant difference between RA patients and controls as regards amplitude. The absolute amplitude is not considered as an important factor in the differential diagnosis due to the large variation range that varies from 25 to 250 μv. In addition, the VEMP amplitude depends on sound intensity and contraction of sternocleidomastoid muscle.
All RA patients in this study showed absence of spontaneous gaze-evoked positional and positioning nystagmus, which indicated that there was no acute vestibular disease and this means that vestibular dysfunction in RA could be associated with the chronic inflammatory process of the disease and this agrees with the findings of Yilmaz et al. In this study, the oculomotor test revealed normal saccade velocity, accuracy, and latency. Eye tracking and optokinetic tests also were normal. These findings exclude the presence of central oculomotor tract affection. Bi-thermal caloric irrigation revealed that 12 patients had unilateral caloric weakness, while it was found to be within normal limits in all controls. Accordingly, the combined absence of spontaneous, positioning, and positional nystagmus together with normal oculomotor test findings in the presence of abnormal caloric test results reflects the peripheral nature of vestibular system affection in RA patients. These results were in agreement with the results obtained by Kakani et al. who assessed the saccade tracings of 25 patients with RA and found no abnormalities in these tests. In addition, King et al. investigated the vestibulo-ocular reflex, optokinetic reflex, and postural function in twenty patients with RA and concluded that RA was not associated with substantial vestibular dysfunction. These results disagreed with the results of Yilmaz et al. who found central and/or peripheral vestibular dysfunction in 34.7% of the patients with RA. Furthermore, El-Fatta et al. reported central and/or peripheral vestibular dysfunction in 47.7% of the patients with RA. Moreover, recently, El Dessouky et al. found central abnormalities in 12 (30%) patients, peripheral abnormalities in 9 (22.5%) patients, and mixed abnormalities in 1 (2.5%) patient.
These conflicting results may be due to the difference in the number of the patients in these studies. In this study, twenty patients were included, while in that of Yilmaz et al., El-Fatta et al., and El Dessouky et al., 43, 40, and 45 RA patients, respectively, were included, which was quite larger than previously reported series.
None of the patients in this study reported balance instability except one patient. Similar findings were encountered in the study done by Yilmaz et al. They attributed these findings to the slow and gradual affection of the vestibular nerve that would provide efficient time for central compensation mechanisms to operate. Therefore, despite the affection of vestibular nerve in RA patients, they could not experience any vestibular symptoms.
From the previous results, 12 patients who had reduced caloric response had more delayed VEMP latencies on the same side of weakness. On the other hand, most of the patients that had delayed VEMP latencies had normal caloric test. Therefore, some patients could have shown normal caloric responses but abnormal VEMP. Accordingly, in this study, 12 patients had combined superior and inferior vestibular nerve affection in one ear and inferior nerve affection in the other ear. On the other hand, the other 14 patients had inferior nerve affection in both ears.
Age, sex, and duration had no effect on auditory affection, VEMP, and caloric abnormalities in patients with RA and this finding agreed with that of Yilmaz et al. On the other hand, the study group was divided into two groups according to pure tone thresholds as follows: Groups A (normal hearing sensitivity [14 ears]) and Group B (high-frequency SNHL [26 ears]). There were no significant differences between the two groups as regards VEMP latencies and amplitude. In other words, this means that there was no association between cochlear and vestibular affection in our study. The lack of correlation between the dysfunction of the cochlea and vestibular system can be explained by their different vascular supply. Murdin et al., Kakani et al., and King et al. suggested that vestibular system dysfunction in RA is rare and the involvement of the cochlea was more frequent than the involvement of the vestibular system. Yoon et al. found extensive fibrosis and new bone formation in their study of histopathologic examinations of the temporal bone of patients with systemic vasculitis.
There is evidence of peripheral and central vestibular affection in inflammatory diseases such as RA. Possible mechanisms for central involvement are vascular lesions, production of autoantibodies, inflammation due to local cytokine production, and probably an inflammatory demyelinating process of the spinal cord. There was no association between cochlear and vestibular affection in this study. Age, sex, and duration of RA had no effect on auditory affection, VEMP, and caloric abnormalities in patients with RA.
| Conclusion|| |
The findings of the current study add more evidence to the cochlea–vestibular involvement in patients with RA. Audio-vestibular function assessment is highly recommended for all RA patients as a routine examination.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Emery P, Gottenberg JE, Rubbert-Roth A, Sarzi-Puttini P, Choquette D, Taboada VM, et al.
Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study. Ann Rheum Dis 2015;74:979-84.
Majithia V, Geraci SA. Rheumatoid arthritis: Diagnosis and management. Am J Med 2007;120:936-9.
Bongartz T, Nannini C, Medina-Velasquez YF, Achenbach SJ, Crowson CS, Ryu JH, et al.
Incidence and mortality of interstitial lung disease in rheumatoid arthritis: A population-based study. Arthritis Rheum 2010;62:1583-91.
Vela P. Extra-articular manifestations of rheumatoid arthritis. EMJ Rheumatol 2014;1:103-12.
Sahatciu-Meka V, Rexhepi S, Manxhuka-Kerliu S, Rexhepi M. Extra-articular manifestations of seronegative and seropositive rheumatoid arthritis. Bosn J Basic Med Sci 2010;10:26-31.
McCabe BF. Autoimmune sensorineural hearing loss. Ann Otol Rhinol Laryngol 1979;88:585-9.
Murdin L, Patel S, Walmsley J, Yeoh LH. Hearing difficulties are common in patients with rheumatoid arthritis. Clin Rheumatol 2008;27:637-40.
Emamifar A, Hansen IM. An update on hearing impairment in patients with rheumatoid arthritis. J Oto 2018;13:1-4.
Huang CM, Chen HJ, Huang PH, Tsay GJ, Lan JL, Sung FC, et al.
Retrospective cohort study on risk of hearing loss in patients with rheumatoid arthritis using claims data. BMJ Open 2018;8:e018134.
García Callejo FJ, Conill Tobías N, Muñoz Fernández N, de Paula Vernetta C, Alonso Castañeira I, Marco Algarra J. Hearing impairment in patients with rheumatoid arthritis. Acta Otorrinolaringol Esp 2007;58:232-8.
Dalton DS, Cruickshanks KJ, Klein BE, Klein R, Wiley TL, Nondahl DM, et al.
The impact of hearing loss on quality of life in older adults. Gerontologist 2003;43:661-8.
Theander L, Nyhäll-Wåhlin BM, Nilsson JŠ, Willim M, Jacobsson LTH, Petersson IF, et al.
Severe extraarticular manifestations in a community-based cohort of patients with rheumatoid arthritis: Risk factors and incidence in relation to treatment with tumor necrosis factor inhibitors. J Rheumatol 2017;44:981-7.
Ferrara P, Modica A, Adelfio M, Sallì L, Pappalardo A. Audio-vestibular changes in patients with rheumatoid arthritis. Minerva Med 1988;79:1043-7.
Yilmaz S, Erbek S, Erbek SS, Ozgirgin N, Yucel E. Abnormal electronystagmography in rheumatoid arthritis. Auris Nasus Larynx 2007;34:307-11.
El Dessouky TM, Abu El Khair E, Koura RA, El Sharkawy S. Assessment of the audiovestibular system in patients with rheumatoid arthritis. EJO 2017;4:650-5.
Kakani RS, Mehra YN, Deodhar SD, Mann SB, Mehta S. Audiovestibular functions in rheumatoid arthritis. J Otolaryngol 1990;19:100-2.
King J, Young C, Highton J, Smith PF, Darlington CL. Vestibulo-ocular, optokinetic and postural function in humans with rheumatoid arthritis. Neurosci Lett 2002;328:77-80.
Heydari N, Hajiabolhassani F, Fatahi J, Movaseghi S, Jalaie S. Vestibular evoked myogenic potentials in patients with rheumatoid arthritis. Med J Islam Repub Iran 2015;29:216.
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd
, et al.
2010 rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Arthritis Rheum 2010;62:2569-81.
Rigual NR. Otolaryngologic manifestations of rheumatoid arthritis. Ear Nose Throat J 1987;66:436-9.
Ruckenstein MJ. Autoimmune inner ear disease. Curr Opin Otolaryngol Head Neck Surg 2004;12:426-30.
El-Fatta EA, Abda EA, Herdan O. Assessment of vestibular system in patients with rheumatoid arthritis (RA) using electronystagmography (ENG). Med J Cairo Univ 2011;79:77-86.
Oztürk A, Yalçin S, Kaygusuz I, Sahin S, Gök U, Karlidağ T, et al.
High-frequency hearing loss and middle ear involvement in rheumatoid arthritis. Am J Otolaryngol 2004;25:411-7.
Halligan CS, Bauch CD, Brey RH, Achenbach SJ, Bamlet WR, McDonald TJ, et al.
Hearing loss in rheumatoid arthritis. Laryngoscope 2006;116:2044-9.
Heyworth T, Liyanage SP. A pilot survey of hearing loss in patients with rheumatoid arthritis. Scand J Rheumatol 1972;1:81-3.
Dikici O, Muluk NB, Tosun AK, Unlüsoy I. Subjective audiological tests and transient evoked otoacoustic emissions in patients with rheumatoid arthritis: Analysis of the factors affecting hearing levels. Eur Arch Otorhinolaryngol 2009;266:1719-26.
Jung TT, Rhee CK, Lee CS, Park YS, Choi DC. Ototoxicity of salicylate, nonsteroidal antiinflammatory drugs, and quinine. Otolaryngol Clin North Am 1993;26:791-810.
Murofushi T, Shimizu K, Takegoshi H, Cheng PW. Diagnostic value of prolonged latencies in the vestibular evoked myogenic potential. Arch Otolaryngol Head Neck Surg 2001;127:1069-72.
Yoon TH, Paparella MM, Schachern PA. Systemic vasculitis: A temporal bone histopathologic study. Laryngoscope 1989;99:600-9.
Bruns A, Meyer O. Neuropsychiatric manifestations of systemic lupus erythematosus. Joint Bone Spine 2006;73:639-45.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]