INTRODUCTION AND LITERATURE REVIEWAuditory evoked potentials can be classified according to latency (time interval between presentation of sound stimulus and wave peak) in 3 groups:
short latency potentials: occur within the first 10 to 12 milliseconds (ms)
medium latency potentials: occur within 12 to 50 ms
long latency potentials: occur within 50 to 600 ms
Brainstem auditory evoked potential (ABR) is a short latency potential that generates a series of waves classified as I to VII, which occur within he first 10 ms after sound stimulus presentation. The waves are generated by sequential activation of the structures through the auditory pathway and captured by electrodes placed on the skin 1.
Aiming at determining wave generating sites, Starr and Hamilton2 correlated ABR data of 10 patients with brainstem damage, confirmed by surgery or necropsy, and concluded that: wave I reflected the activity of auditory nerve, waves II and III, the activity of the cochlear nucleus, corpus trapezoid, and superior olivary complex, and waves IV and V reflected the activity of the lateral lemniscus and inferior colliculus. More recent studies 3, 4 suggested the following wave locations: wave I - distal portion of the auditory nerve; wave II - proximal portion of the auditory nerve; wave III - cochlear nuclei; wave IV - superior olivary complex; wave V - lateral lemniscus; waves VI and VII - inferior colliculus.
ABR is an objective non-invasive method that allows neurophysiological analysis of auditory pathway, from the inner ear to high brainstem.
The use of sensation level (SL) as the unit of ABR stimulation aims at correcting the individual differences of pure tone thresholds to provide constant sound stimulus to the auditory pathways, and therefore, equalize the differences of thresholds that occur as a result of aging. SL is based on the auditory threshold found to a specific type of sound stimulus. To the threshold, we should add constant intensity of the stimulus that normally ranges from 60dB to 70dB.
Eggermont and Don5 studied the effect of intensity of wave clicks in ABR and found clear responses only with 60dB stimuli. Only after this intensity, waves I, III and V were clear and reproducible. In 20dB SL, for example, only wave V was easily identified. Using a population of 11 women and 10 men, Fuzimoto6 standardized ABR using SL as the stimulation unit at Hospital Universitário Clementino Fraga Filho.
Each center should define its own normal range values, since latencies depend on many factors, such as stimulus parameters, the device used and the population characteristics of gender and age 7.
Age is referred to as a variable that modifies ABR findings in childhood, but its real influence in adult life stills remains controversial, reinforcing the importance of studies that address the issue.
ABR assessment in children and adults confirmed the inverse relation between intensity of stimulus and wave V latency and showed that wave V latency reduced progressively from birth to finally reaching the values of an adult at about 12 to 18 months of age, suggesting that the level of nervous fiber myelinization and immaturity of the auditory pathways would affect wave latency 8, 9.
ABR of men and women with normal hearing shows a significant difference between wave latencies. Latencies are shorter in women when compared to men 10-15.
Some authors described a delay in absolute latency in all components of ABR in elderly patients 14, 16-19, 25.
Prebycusis caused by peripheral processes can lead to increase in ABR wave absolute latency, but maintaining interpeak latency (LIP) 11, 17, 18, 23, 24, 26.
Other authors, however, upon studying the age correlation with ABR did not find statistically significant differences in wave latency 19, 20, 24.
Wharton and Church22 assessed ABR in 40 subjects with normal hearing, being 10 young women (19-25 years), 10 women in the menopause without hormone replacement (50-70 years), 10 young men (19-25 years) and 10 men aged 50 to 70 years, in order to assess the influence of gender on ABR. They found increased latencies in men compared to women. In post-menopause women, latency was higher than in pre-menopause subjects, suggesting that hormone affections represented especially in low plasma levels of estrogen, can influence these findings.
Freitas and Oliveira28 assessed ABR in 60 subjects of both genders at 90dB HL intensity with 50dB masking. Subjects were divided into 6 groups according to age range, being half female and half male subjects. They found tendency to increase wave I latency and wave V as a result of aging, especially in subjects with presbycusis.
The present study aimed at analyzing and comparing the absolute latency values of waves I, III and V and interpeak latency I-III, III-V, I-V of ABR in a group of subjects aged 20 to 30 years and in a group of subjects over the age of 60 years, using SL as stimulus unit, in order to assess whether age is a factor that significantly influences these results.
MATERIAL AND METHODThe present study was conducted in the Division of Special Methods (SME) of Otorhinolaryngology, UFRJ.
The study comprised 30 male subjects, being 15 aged 20 to 30 years (group I) and 15 aged over 60 years (group II). The subjects were selected at HUCFF, among the patients of the Ambulatory of Otorhinolaryngology, Medical School undergraduates and employees at UFRJ.
All subjects were previously informed about the study objectives, as well as the procedures involved and they consented to participate in the study. The research protocol was analyzed and approved by the Ethics Committee of HUCFF, complying with all the requirements necessary to conduct a clinical trial in human beings.
All subjects underwent otoscopy and pure tone audiometry in frequencies of 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 3000 Hz, 4000 Hz, 6000 Hz and 8000 Hz, with auditory thresholds for pure tone that were equal or better than 40dB hearing level (HL). We excluded from the study patients that presented clinical history of otological or neurological disease, past history of diabetes mellitus, blood hypertension, syphilis, or head trauma.
The tests were conducted in a sound and electrical proof room, under controlled lighting and temperature of about 25o C. First, we identified thresholds for click in each ear in peSPL. To these stimuli, we added 70dB peSPL determining the stimulus intensity in SL to be employed by each ear in ABR. The contralateral ear to the sound stimulus was masked with white noise 40 dB SPL below that of the intensity of the stimulus used.
ABR was conducted using a device brand Amplaid, model MK15, with headsets TDH-49, which is located at SME, HUCFF, with calibration conducted at the beginning of the study and regularly monitored throughout the study time.
Next, the volunteers were positioned in comfortable dorsal position on an examination bed in order to allow appropriate muscle relaxation. During the exam, they had closed eyes, many times reaching natural sleep. None required sedation. After cleaning the skin with alcohol-ether solution at 50% and applying abrasive paste, 0.5cm diameter shell-shaped surface gold electrodes were fixed using electrolytic betonite paste and adhesive tape. As to position of electrodes to conduct the test, we used configuration of 3 channels. The grounding electrode was placed in the mentalis region, negative electrodes (A2 and A1) related to the right ear and left leaf, respectively, were fixed on the anterior aspect of the respective earlobe. Positive electrode (Fpz) was fixed on the forehead, at the level of the saggital plan, close to the hairline. When we stimulated RE, correlation Fpz-A2 was considered as ipsilateral recording and Fpz-A1 had contralateral recording. The opposite happened when stimulating the LE. Horizontal recording was related to correlation A2-A1. We only accepted electrode impedance below 5 KOhms and the inter-electrode difference was below 3 KOhms.
ABR was conducted using a non-filtered click as stimulus, with 100 µs, negative polarity (rarified) at a stimulus speed of 11 clicks/s and previously determined intensity for each ear, in SL. The investigation was always monaural, starting from the right ear, in a total of 2,000 stimuli. The period of analysis was 12 ms. The duplication of each recording was conducted in order to ensure wave reproducibility and reliability.
We used ipsilateral, contralateral and horizontal correlations. Latency values were recorded from ipsilateral measures only, whereas the other recordings were used only to facilitate identification of the waves.
For each test, we used absolute latency values in ms of waves I, III and V as well as LIP II, III-V and I-V for each ear. Later, the waves were definitely printed on paper so that it could be used in the study.
The values were submitted to statistical analysis by the Scientific Investigation Commission, HUCFF.
We analyzed absolute latency values of waves I, III and V, and LIPs I-III, III-V and I-V using t Student test for independent samples, in order to compare the two studied groups. Mann-Whitney test was used to analyze the click intensity data and stimulus intensity in the ABR study.
The criterion to determine significance was 5%, that is, when p value in the statistical test was equal or below 0.05, there was statistically significance (p<0.05). The statistical analysis was processed by statistical software. Data were expressed in mean, standard deviation (DP), minimum and maximum for each Group.
RESULTSThe analysis of ABR recordings was made in 30 subjects, being 15 aged 20 to 30 years (group I) and 15 older than 60 years (group II). The mean age of group I was 24 years and the mean age of group II was 65.6 years (table 1).
The study started by determining the mean of thresholds for clicks in individual subjects. The mean thresholds for group I was 40.8dB peSPL and for group II it was 54.8 peSPL (table 2).
In all tests, waves I, III and V were easily defined and reproduced. There was no atypical morphology or wave desynchronization.
Later on, we analyzed latency of waves I, III and V and LIPs I-III, III-V and I-V in each ear using t Student test for independent samples. The values of each wave and LIPs in the two studied groups are presented in mean, DP and p value (Table 3).
DISCUSSIONIn this study, we analyzed only male patients since in men absolute latencies are higher than in women 10-13. Allison et al.7 complained of increase in latency of all waves in men compared to women, especially that of wave V, suggesting the analysis of genders separately. These increases were related to anatomical differences in the head region of both genders, a fact that was not confirmed by Costa Neto et al.12, who studied the influence of gender and head size on ABR latency. Another reason for choosing only male subjects was to exclude the hormone effect of menopause as a confounding factor. There are significant hormone differences in women aged 20 to 30 years and women aged 60 years, especially concerning plasma estrogen levels. Wharton and Church22 reported affections of wave latency of ABR in women in menopause resultant from hormone affections.
Intensity of stimulus was 70dB SL, that is, 70 dB above psychoacoustic threshold for clicks, as a result of expected responses. Eggermont and Don5 showed that below 60dB SL it was not possible to have a perfect identification of waves I, III and V.
Age is an important variable in the analysis of ABR in children. Normal children below the age of 24 months can present increased latency in all ABR waves, an increase which is evidenced in wave V. Hecox and Galambos8, Lima9 suggested that changes related to age in this age range tend to reflect the maturational development of cochlear and neural generators of ABR.
The effects of age in ABR in adults are more undefined and polemical. Howe 16, Harkins18, Jerger and Hall14 showed that wave V latency of ABR increases systematically with aging. The study by Rowe16 was interpreted as indicative of delay in conduction in the pontine-medullary region as a result of aging, but still maintaining good conduction in the brainstem area. However, the study by Rowe compared 25 patients aged between 51 and 74 years with 25 young patients and included in his work patients with presbycusis.
The study conducted by Luccas, Manzano, Ragazzo20 analyzed 10 normal subjects of both genders aged 25-49 years using 60dB as stimulation unit. It was one of the few studies that used SL as the stimulus unit and, similarly to ours, it did not show differences in absolute latency and interpeak latency of the studied population.
Rosenhall et al.11, Ottaviani et al.24, Freitas and Oliveira28 evidenced that hearing loss related to age (presbycusis) was described in ABR as reduction of electrophysiological thresholds, increase in latency and/or reduction of wave amplitude in humans and animals. For this reason, it is not recommendable to compare young patients with elderly patients that present presbycusis.
Beagley and Sheldrake10 studied 70 subjects with normal hearing aged 14 to 79 years, being 50% male and 50% female subjects, and similarly to our study, the authors did not find effect of age on absolute latency or LIPs.
Macedo15 showed that effects of age on ABR are minimum on the 6th and 7th decades of life, especially when the effects of presbycusis are controlled. For this reason, our study used SL as the stimulation unit, so that we could correct individual differences of pure tone thresholds in order to provide constant sound stimulus to auditory pathways and equalize the differences in thresholds that occurred with aging. Such precaution was not followed by Rowe16 in his study that used patients with hearing loss and did not use SL to correct the loss.
The thresholds for clicks found in our study ranged from 40 to 45dB peSPL (mean of 40.8 dB) in group I and between 50 and 60dB peSPL (mean of 54.8 dB) in group II. This finding was compatible with the study by Fuzimoto6 that used SL as the stimulation unit, analyzing 11 male patients with normal hearing and ages ranging from 20 to 37 years, and found thresholds for clicks ranging from 35 to 55 dB peSPL (mean of 40.5 dB).
In our study, we did not find statistically significant difference in ABR findings in any of the studied parameters comparing men aged 60 years to people aged 20-30 years. We would like to emphasize that in our study we were careful to exclude all patients with presbycusis, hypertension, diabetes mellitus and neurological diseases, in addition to having used SL as the stimulation unit in order to avoid confounding factors in study findings.
The controversial issues in the literature concerning the studies with ABR and age in adults can be owed to the different selection criteria employed, especially concerning health status, subjects' gender and the stimulation unit used.
CONCLUSIONThe results of the present study led us to the conclusion that there is no statistically significant difference in absolute latency of waves I, III and V, nor LIPs I-III, III-V and I-V in ABR in men aged 20 to 30 years when compared to men aged over 60 years, using sensation level as stimulus.
Table I. Mean age of volunteers between 20 and 30 years (Group I) and after 60 years (Group II).
N = number of patients
DP = standard deviation
Table II. Mean thresholds for clicks in peSPL in volunteers aged 20 - 30 years (Group I) and over 60 years (Group II).
N = number of ears
DP = standard deviation
Table III. Mean and standard deviation of absolute latency values of waves I, III and V and LIPs I-III, III-V and I-V in milliseconds (ms) in volunteers aged 20 to 30 years (Group I) and over the age of 60 years (Group II).
DP = standard deviation
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1 Master in Otorhinolaryngology, Medical School, Federal University of Rio de Janeiro (UFRJ).
2 Joint Professor, Discipline of Otorhinolaryngology, FM, UFRJ.
3 Faculty Professor, Discipline of Otorhinolaryngology, FM, UFRJ.
Study conducted at the Service of Otorhinolaryngology, Hospital Universitário Clementino Fraga Filho (HUCFF), UFRJ and part of the master dissertation submitted on 19/02/2003 to be approved as Master in Otorhinolaryngology.
Address correspondence to: Christiane Ribeiro Anias - Rua dos Artistas 355/201 Tijuca Rio de Janeiro RJ 20511-130
Tel (55 21) 2572-0692 - E-mail: chrisra@terra.com.br
This study was financially supported by CAPES.