Abstract
Objective
To investigate vestibular evoked myogenic potentials combined with audiologic status in Behcet’s disease (BD) and to compare the results with normal healthy subjects.
Methods
Cervical vestibular evoked myogenic potential (cVEMP) test, ocular vestibular evoked myogenic potential (oVEMP) test, Dix–Hallpike test, conventional pure tone audiometry (cPTA) and high frequency audiometry (HFA), and 226 and 1000 Hz tympanometry were performed to each subject of the study. Cranial magnetic resonance imaging (MRI) with contrast enhancement was also performed to evaluate the central nervous system (CNS) in patients with BD.
Results
VEMP parameters including the mean peak latencies of p13-n23 and n10-p15, AR values and thresholds were not statistically different both in cVEMP and oVEMP between the BD and control groups. Except for 250 Hz, mean audiological thresholds were significantly higher in the BD group. Five of the 20 patients had pathological cranial MRI findings that may be compatible with central nervous system involvement.
Conclusion
To our knowledge, the present study is the first report investigating oVEMP and cVEMP responses combined with MRI findings in patients with BD. The presence of high frequency hearing loss is a common finding in BD and HFA may help early detection of hearing loss in patients with BD when combined with cPTA.
1
Introduction
Behcet’s disease (BD) is a systemic, immune mediated vasculitis that was first described by Hulusi Behcet in 1937 . The etiology and pathogenesis of BD are unknown but interactions between genetic and environmental factors may play a role in the expression and prevalence of the disease. BD has an endemic distribution along the ancient Silk Road and occurs at a rate of 37/10,000 in Turkey, which is the highest prevalence worldwide. It commonly presents around the third decade of life with no gender predominance .
The International Study Group of BD published the diagnostic criteria of BD in 1990. Oral ulceration plus two of the following constitute the diagnosis: genital ulceration, eye lesion, skin lesion, or positive pathergy test . Although diagnosis is mainly based on these criteria, BD may affect almost any part of the body. Audiovestibular involvement was first described by Alajouanine et al. in 1961 . Audiovestibular system involvement in BD has been previously reported by many authors in several reports, which ranged from 12 to 80% for hearing impairment and from 20 to 40% for vestibular symptoms.
Vestibular evoked myogenic potentials (VEMPs) are short latency electromyographic responses to high intensity sound stimuli that may reflect the saccule function, termed cervical VEMP (cVEMP), as well as utricular function, termed ocular VEMP (oVEMP). The electromyographic responses show a biphasic waveform in healthy subjects with an initial positivity (p13) and subsequent negativity (n23) in cVEMP. In contrast, oVEMP responses are characterized by an initial negative peak (n10) followed by a positive peak (p15) .
In the present study, we aimed to evaluate both cVEMP and oVEMP recordings in patients with BD and compare the results with normal healthy subjects. Cranial magnetic resonance imaging (MRI) with contrast enhancement was also performed to evaluate the central nervous system (CNS) in patients with BD. Audiologic tests, including conventional pure tone audiometry (cPTA) and high frequency audiometry (HFA), and 226 and 1000 Hz tympanometry, were also performed to examine the audiologic status due to the inseparable integrity of the audiovestibular system.
2
Materials and methods
The BD group consisted of 30 patients with BD who were regularly followed by the Romatology Department of the Kayseri Training and Research Hospital. All the patients fulfilled the criteria published by the International Study Group of BD . Thirty healthy, normal, age and sex-matched subjects were recruited as a control group.
A detailed medical history, including audiovestibular and neurological symptoms, was taken from patients with BD. Age, sex, duration of the disease and organ or system involvement were reviewed from the medical records of the patients. Patients with any metabolic, autoimmune, or connective tissue disorder that might be associated with sensorineural hearing loss (SNHL), ototoxic drug use, a history of any head or ear trauma including exposure to noise and any otologic or neurologic disease unrelated to BD were excluded from the study. Written informed consent was obtained from the subjects and the study protocol was approved by the Ethics Committee of the Kayseri Erciyes University School of Medicine.
All patients with BD and control subjects underwent physical and otolaryngological examinations. Vestibular evaluation was begun with examination of spontaneous and gazing nystagmus, followed by Dix–Hallpike test. Contrast enhanced cranial MRI was acquired from the patients with BD to examine the central nervous system. VEMP procedures were performed with a Neuro-Audio (Version 2010, Neurosoft, Ivanovo, Russia) device. Short-tone burst stimulations were delivered to each ear via TDH-39P acoustically shielded headphones (Interacoustics A/S, Denmark) during the VEMP procedures. The stimulation rate was 5 Hz and the analysis time window was 50 ms. A total of 128 stimuli were applied to each ear and repeated two consecutive times to confirm test wave reproducibility.
Patients were tested in a sitting position during the cVEMP procedure. The active electrode was put on the upper half of the SCM ipsilateral to the sound stimulation, with the reference electrode on the sternoclavicular junction and the ground electrode on the forehead. Patients were asked to turn their heads contralaterally to keep the SCM muscle contracted. EMG signals were amplified and bandpass-filtered between 30 and 2000 Hz. Short-tone burst stimulations (110 dB nHL, 500 Hz, each with a 2-ms rise fall time and a 0-ms plateau time) were delivered to each ear. The peak latencies of p13 and n23 were measured and the amplitude asymmetry ratio (AR) was calculated as follows: (larger response-smaller response)/(larger response + smaller response) × 100 . In the present study, AR values were used for interpretation of the VEMP amplitude, since VEMP amplitudes are significantly affected by the force of muscular contraction or stimulus intensity and exhibit wide variation. The test sequence for each frequency began at a maximum intensity of 110 dB nHL, which was reduced in 5–10 dB decrements until the reflex disappeared to obtain the reflex threshold of each ear.
The oVEMP test procedure was performed in a sitting position. The electromyographic activities of extraocular muscles were recorded via surface electrodes that were placed around 1 cm below the center of the two lower eyelids. The other two reference electrodes were put approximately 1–2 cm below the active electrodes and the ground electrode was placed on the forehead. Patients were asked to look upward at a small target located 2 m away and 30 0 above the horizontal line during the test. EMG signals were amplified and bandpass filtered between 1 and 1000 Hz. Sound stimuli were delivered to the contralateral side of the active electrode with an intensity of 110 dB nHL and oVEMP responses were obtained only from the eye contralateral to the stimulated ear. Peak latencies of n10 and p15, AR and reflex thresholds were measured.
The mean peak latencies of p13/n23 and n10/p15 were calculated in the control group and the latencies above the mean values + 2SD were considered as a delayed response. Decreased VEMP response was determined when the AR value was larger than mean + 2SD of normal controls. The mean peak latencies of p13/n23 and n10/p15 in the control group were 14.1 ± 1.8/21.5 ± 1.9 and 10.1 ± 1.2/15.4 ± 1.3, respectively. The values of the latency of p13/n23 above 17.7/25.3 ms (mean + 2SD), and the latency of n10/p15 above 12.5/18 (mean + 2SD) were considered as a delayed response. The mean values of AR in the control group for cVEMP and oVEMP were 15.4 ± 14.1% and 33.4 ± 25.3%, respectively. The values of AR exceeding 43.78% (mean + 2SD) for cVEMP, and the values of AR exceeding 71.3% (mean + 2SD) for oVEMP were determined as a decreased VEMP response. Abnormal VEMP response was defined when any subject of the study exhibits a delayed, absent or a decreased responses.
Conventional pure tone audiometry (0.25, 0.5, 1, 2, 4 and 8 kHz) and HFA (10, 12.5, 14 and 16 kHz) were performed for each subject in the study in a standard soundproof room with a Grason–Stadler GSI-61 clinical audiometer (Madison, WI). Acoustic thresholds greater than 25 dB at any frequency were considered as SNHL. Individual values of hearing thresholds in 10, 12.5, 14, 16 kHz were used to assess hearing level for high frequencies. Standard 226 Hz and also 1000 Hz tympanometric analyses were conducted via an AT235h Impedance Audiometer (Interacoustics A/S, Denmark). Subjects with a value of middle ear pressure lower than − 50 mm H 2 O were excluded from the study.
Statistical analysis was performed using Statistical Package for the Social Sciences (v. 15; SPSS Inc.; Chicago; IL). The independent-samples t test was used to compare the parametric conditions of two groups and chi-square for comparison of categorical variables. Mann–Whitney U test was carried out for nonparametric conditions. A p value less than 0.05 was considered significant for all comparisons.
2
Materials and methods
The BD group consisted of 30 patients with BD who were regularly followed by the Romatology Department of the Kayseri Training and Research Hospital. All the patients fulfilled the criteria published by the International Study Group of BD . Thirty healthy, normal, age and sex-matched subjects were recruited as a control group.
A detailed medical history, including audiovestibular and neurological symptoms, was taken from patients with BD. Age, sex, duration of the disease and organ or system involvement were reviewed from the medical records of the patients. Patients with any metabolic, autoimmune, or connective tissue disorder that might be associated with sensorineural hearing loss (SNHL), ototoxic drug use, a history of any head or ear trauma including exposure to noise and any otologic or neurologic disease unrelated to BD were excluded from the study. Written informed consent was obtained from the subjects and the study protocol was approved by the Ethics Committee of the Kayseri Erciyes University School of Medicine.
All patients with BD and control subjects underwent physical and otolaryngological examinations. Vestibular evaluation was begun with examination of spontaneous and gazing nystagmus, followed by Dix–Hallpike test. Contrast enhanced cranial MRI was acquired from the patients with BD to examine the central nervous system. VEMP procedures were performed with a Neuro-Audio (Version 2010, Neurosoft, Ivanovo, Russia) device. Short-tone burst stimulations were delivered to each ear via TDH-39P acoustically shielded headphones (Interacoustics A/S, Denmark) during the VEMP procedures. The stimulation rate was 5 Hz and the analysis time window was 50 ms. A total of 128 stimuli were applied to each ear and repeated two consecutive times to confirm test wave reproducibility.
Patients were tested in a sitting position during the cVEMP procedure. The active electrode was put on the upper half of the SCM ipsilateral to the sound stimulation, with the reference electrode on the sternoclavicular junction and the ground electrode on the forehead. Patients were asked to turn their heads contralaterally to keep the SCM muscle contracted. EMG signals were amplified and bandpass-filtered between 30 and 2000 Hz. Short-tone burst stimulations (110 dB nHL, 500 Hz, each with a 2-ms rise fall time and a 0-ms plateau time) were delivered to each ear. The peak latencies of p13 and n23 were measured and the amplitude asymmetry ratio (AR) was calculated as follows: (larger response-smaller response)/(larger response + smaller response) × 100 . In the present study, AR values were used for interpretation of the VEMP amplitude, since VEMP amplitudes are significantly affected by the force of muscular contraction or stimulus intensity and exhibit wide variation. The test sequence for each frequency began at a maximum intensity of 110 dB nHL, which was reduced in 5–10 dB decrements until the reflex disappeared to obtain the reflex threshold of each ear.
The oVEMP test procedure was performed in a sitting position. The electromyographic activities of extraocular muscles were recorded via surface electrodes that were placed around 1 cm below the center of the two lower eyelids. The other two reference electrodes were put approximately 1–2 cm below the active electrodes and the ground electrode was placed on the forehead. Patients were asked to look upward at a small target located 2 m away and 30 0 above the horizontal line during the test. EMG signals were amplified and bandpass filtered between 1 and 1000 Hz. Sound stimuli were delivered to the contralateral side of the active electrode with an intensity of 110 dB nHL and oVEMP responses were obtained only from the eye contralateral to the stimulated ear. Peak latencies of n10 and p15, AR and reflex thresholds were measured.
The mean peak latencies of p13/n23 and n10/p15 were calculated in the control group and the latencies above the mean values + 2SD were considered as a delayed response. Decreased VEMP response was determined when the AR value was larger than mean + 2SD of normal controls. The mean peak latencies of p13/n23 and n10/p15 in the control group were 14.1 ± 1.8/21.5 ± 1.9 and 10.1 ± 1.2/15.4 ± 1.3, respectively. The values of the latency of p13/n23 above 17.7/25.3 ms (mean + 2SD), and the latency of n10/p15 above 12.5/18 (mean + 2SD) were considered as a delayed response. The mean values of AR in the control group for cVEMP and oVEMP were 15.4 ± 14.1% and 33.4 ± 25.3%, respectively. The values of AR exceeding 43.78% (mean + 2SD) for cVEMP, and the values of AR exceeding 71.3% (mean + 2SD) for oVEMP were determined as a decreased VEMP response. Abnormal VEMP response was defined when any subject of the study exhibits a delayed, absent or a decreased responses.
Conventional pure tone audiometry (0.25, 0.5, 1, 2, 4 and 8 kHz) and HFA (10, 12.5, 14 and 16 kHz) were performed for each subject in the study in a standard soundproof room with a Grason–Stadler GSI-61 clinical audiometer (Madison, WI). Acoustic thresholds greater than 25 dB at any frequency were considered as SNHL. Individual values of hearing thresholds in 10, 12.5, 14, 16 kHz were used to assess hearing level for high frequencies. Standard 226 Hz and also 1000 Hz tympanometric analyses were conducted via an AT235h Impedance Audiometer (Interacoustics A/S, Denmark). Subjects with a value of middle ear pressure lower than − 50 mm H 2 O were excluded from the study.
Statistical analysis was performed using Statistical Package for the Social Sciences (v. 15; SPSS Inc.; Chicago; IL). The independent-samples t test was used to compare the parametric conditions of two groups and chi-square for comparison of categorical variables. Mann–Whitney U test was carried out for nonparametric conditions. A p value less than 0.05 was considered significant for all comparisons.
3
Results
The BD group consisted of 19 women and 11 men, whereas the control group consisted of 17 women and 13 men. The mean age of the BD and control groups was 40.7 (range 21–62) and 39.7 years (range 18–63), respectively. There was no statistically significant difference between the two groups with regard to age and sex (p > 0.05). The mean duration of disease in the BD group was 8.58 years (range 1–23 years).
Twenty-one (70%) patients reported complaints of dizziness, which subsided within a few seconds. Spontaneous or gazing nystagmus was not detected in any subjects. Dix–Hallpike tests were within normal limits for all subjects. VEMP parameters did not show any statistical difference between right and left ears (p > 0.05). VEMP responses were elicited in each subject for cVEMP while those were absent in two subjects for oVEMP in the control group. The response rate was 100% and 93.3% for cVEMP and oVEMP responses, respectively. The response rate was 90% for cVEMP and oVEMP each in BD group. The mean latencies of cVEMP (p13-n23) and oVEMP (n10-p15) were not significantly different between the two groups. AR values were higher in the BD group but the difference was not statistically significant. The differences between the two groups in terms of cVEMP and oVEMP thresholds were not significantly different. The values of VEMP parameters and statistical evaluations are shown in Table 1 .
