Open Journal Systems

ORIGINAL CONTRIBUTIONS

Received: December 15^th /2014

Accepted: April 16^th 2015

Brainstem auditory evoked potentials latencies, by age and sex, among mexican adult population

Guadalupe Aguilar-Madrid,^a Arturo Torres-Valenzuela,^b Wendoly Hinojos-Escobar,^c Alejandro Cabello-López,^a Rodrigo Gopar-Nieto,^d Perla Estela Ravelo-Cortés,^a Luis Cuauhtémoc Haro-García,^a Cuauhtémoc Arturo Juárez-Pérez^a

^aUnidad de Investigación de Salud en el Trabajo, Centro Médico Nacional Siglo XXI, Ciudad de México

^bServicio de Audiología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México

^cServicio de Audiología, Hospital Regional 1, Unidad Morelos, Chihuahua, Chihuahua

^dServicio de Medicina Interna, Hospital Lic. Adolfo López Mateos, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México

^a-cInstituto Mexicano del Seguro Social, Ciudad de México, México

Communication with: Cuauhtémoc Arturo Juárez-Pérez

Telephone: (55) 5761 0725

Email: carturojp@gmail.com

Background: Brainstem auditory evoked potentials (BAEP) evaluate the auditory pathway, and are a complementary test for tone audiometry in evaluating auditory diseases. The aim of the study was to determine BAEP mean latencies of waves and intervals, among healthy adults.

Methods: Cross-sectional study, comprising 196 subjects, aged 16 to 65 years, without auditory diseases, to whom family and personal history were asked, physical examination and laboratory studies were made, as well as tonal audiometry, impedanciometry and BAEP.

Results: A total of 107 men and 89 women were studied. The mean latency periods of waves I, III and V, and intervals I-III, III-V and I-V from both ears were similar. An increase in the latency periods for each age category was observed. Latency periods were significantly shorter in women compared to men. The predictors that increased the latency periods in the multiple linear regression models for waves and intervals were male gender and age ≥45 years.

Conclusions: Age and sex were the variables that showed more statistical power to explain the latencies’ differences.

Keywords: Auditory evoked potentials; Brain stem; Audiology; Auditory pathways

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Brainstem auditory evoked potentials (BAEP) represent the response of the central nervous system to an acoustic stimulus.¹ They are composed of five to seven spikes that can be detected in the first 12 milliseconds (ms) after the onset of the stimulus. Neurons process these stimuli along the auditory afferent pathway in the following structures: wave I, in the proximal region of the eighth cranial nerve; wave II, in the cochlear nucleus; wave III, in the superior olivary complex; wave IV, in the lateral lemniscus; wave V, in the inferior colliculus; wave VI, in the medial geniculate body; and wave VII in the auditory temporal cortex.^1-3 In electrophysiology, only the overall responses are measured; to achieve this goal an acoustic stimulus is used, called click, which has a determined frequency and intensity.⁴  

Although tone audiometry is the gold standard to assess hearing, it does not provide information about retrocochlear effects or central auditory processes, so it is late to evidence hearing damage.⁵ In this sense, BAEPs can identify and locate auditory pathologies and dysfunctions in specific regions of the auditory pathway, in addition to sensory disturbances when the clinical presentation and neurological examination are unclear, and they reveal the presence of problems in the central nervous system when a demyelinating disease is suspected. The main advantages of using BAEP include independent interpretation of the subjectivity of the operator, the cognitive status of the patient, the influence of educational and cultural factors,⁷ and minimal modification from the neurological status and awareness of the patient.⁸

Clinically, the most important waves are the waves I, III, and V.³ However, there are conditions such as age,⁹ sex,¹⁰ chronic diseases (diabetes, hypertension, dyslipidemia), social behaviors, and occupational risks (organic solvents, heavy metals, and pesticides) to be assessed to know their influence and determine reference values ​​in populations studied.^8,11,12

The urgent need to standardize BAEP values​​ is intrinsically related to neurological and electrical characteristics, mainly because they are signals measured in a very small range of frequencies, and can be modified by multiple factors. Unfortunately, in Mexico there are no reference values ​​for PEATC in the healthy adult population, although there are populations at risk of hearing pathology due to exposure to risk factors such as ototoxic drugs and high noise levels, alone or combined with ototoxic or neurotoxic substances (organic solvents, heavy metals, and pesticides). Therefore, the objective of this study was to determine the mean values ​​of latencies of waves I, III, and V, as well as the intervals I-III, III-V and I-IV, in a healthy adult population categorized by sex and age, and to identify predictors that explain the variability of the BAEP values​​ in this population, in order to obtain reliable reference values ​​in a population of Mexican workers insured by the Instituto Mexicano del Seguro Social (IMSS).

Methods

Study design and participant selection

A cross-sectional study was made involving a sample of Mexican workers affiliated with the Instituto Mexicano del Seguro Social, who were recruited from the Blood Bank of the XXI Centro Médico Nacional Siglo XXI (CMN SXXI) during the period 2009 to 2011. Participants were invited and informed of the protocol and those who agreed to participate in the study signed a letter of informed consent. The study was approved by the Local Research Committee of the Hospital de Especialidades del CMN SXXI. To protect the confidentiality of participants, their names were omitted and an identification number was used. The study criteria were as follows:

• Inclusion criteria: Mexican nationality, age between 16 and 65 years, of both sexes; normal hearing, no hearing diseases corroborated by a medical history including metabolic, otological, trauma, and occupational history; blood chemistry and lipid profile within normal parameters, along with a physical examination, otoscopic and audiologic evaluation within normal parameters (tone audiometry and tympanometry). 
• Exclusion criteria: pregnant patients, people outside the established age ranges, people diagnosed with a chronic disease (hypertension, dyslipidemia, and hyperuricemia), mental disorders, drug use (including binge drinking); occupational exposure to noise, organic solvents, and changes in barometric pressure; history of electric shock, prolonged use of ototoxic drugs, head injuries, otological diseases (acute otitis media, chronic sequelae of otitis media, or tympanic membrane perforation), hematological diseases, or nerve conduction; participants who did not complete at least 80% of the questionnaire or who did not complete audiological evaluations, or if during these any hearing pathology was detected, and those who also decided not to continue the BAEP study.

Evaluations

• Questionnaire: Each participant who gave consent to collaborate in the study provided the following information: demographic data such as age and sex, which were used for the construction of the categories; family, non-pathological, disease, occupational, and environmental history.
• Blood tests: each patient had blood count, blood chemistry, and lipid profile performed. The values ​​established in the clinical analysis laboratory of the CMN SXXI Blood Bank were taken as reference.
• Physical examination: This included the following: a) Blood pressure, measured with an AG1-10 BP sphygmomanometer; b) body temperature, measured with a Hergom CE0197 thermometer; c) Otoscopy, performed with a Welch Allyn 710168-501 otoscope.  
• Tone audiometry: Auditory threshold was measured in a soundproof room, as established by the American National Standards Institute (ANSI), with a two-channel audiometer, Orbiter 922 version 2, calibrated according to ANSI standards 3.1-1996. The auditory threshold was obtained in both ears, in the frequency range of 125-8000 Hz (Hood method), and thresholds > 20 dB were regarded as unusual.
• Impedance measurement: Each patient had tympanometry and ipsilateral acoustic reflex measurement performed. Tympanometry was interpreted according to the Jerger criteria (A, As, Ad, B, C) and the acoustic reflex was reported as present or absent.
• BAEP: was done using the Nicolet Viking Quest Auditory System program in a soundproof room, according to ANSI standards 3.1-1997. The electrodes were placed as indicated by the International System 10-20 (G, Cz, A1, and A2). After explaining the procedure and making the participant comfortable, BAEP was measured, first in the left ear and then in the right ear, following certain stimulation parameters: 2000 clicks of rarefaction at 80 dB, with a stimulation rate of 33 clicks per second, analysis time 10 ms, and a sensitivity of 50 mV.

Statistical analysis

Data were collected in a Microsoft Office Excel spreadsheet, and double data capture was done to avoid errors and inconsistencies in the database. Statistical analysis was performed in STATA version 12. To do this, 4 age groups were created with reference to the quartiles 25, 50, and 75 as follows: ≤ 24, 25-34, 35-44 and ≥ 45 years with the intention of having a similar number of participants in each category. As part of the analysis, frequencies and percentages of variables were determined, as well as measures of central tendency and dispersion, percentiles, and bivariate analysis to observe the behavior of the variable of interest. Student’s t-test, Mann-Whitney U, and ANOVA were used for comparison of means depending on whether the distribution of quantitative variables fulfilled the assumptions of normality; furthermore, Chi-squared independence tests were done for categorical variables. Finally, multiple regression models were performed, adjusted for age and sex to identify the determinants of BAEP variability, which included: noise exposure, alcohol consumption, smoking, blood glucose, and blood lipids. A p < 0.05 was considered statistically significant.

Results

A sample of 196 participants was studied, 107 men (54.6%) and 89 women (45.4%). The power of the sample was calculated considering an alpha = 0.05, which resulted in a 100% power. The mean age for men was 27 ± 9 years and for women 28 ± 10 years. Of the total sample, 114 participants (58.5%) reported family history of hypertension and 121 (62.4%) of diabetes mellitus. In addition, 54 participants (27.7%) reported active smoking and 104 (53.9%) reported occasional alcohol consumption.

The average latencies of waves I, III, and V and intervals I-III, III-V and I-V were similar in both ears. However, a significant increase in latencies of the waves was observed in each age group. In both ears, wave I showed a longer average latency in people ≥ 45 years. However, interval latencies showed no significant increase among the different age categories.

A comparative analysis was performed by sex; in the left ear, women had shorter latency periods compared to men. This pattern was similar in the right ear, but only in wave III (Figures 1 and 2).

According to the analysis by sex and age, significant differences were observed in women in most waves and intervals (Table I). The comparison by sex showed that there are differences in the average time of latencies of all waves and intervals of the right ear, except in wave I (Figures 1 and 2). In the left ear, differences in waves I, III, and V were found, but not in the intervals (Table II).

Multiple linear regression models were performed to identify predictors of variability in latency of the waves and intervals. In this sense, male sex and age ≥ 45 years were the variables that showed statistically significant differences for most waves and intervals included in the models (Table II).

In the model that included sex, average latencies in both ears showed statistically significant differences in waves III and V, as well as the intervals I-III and I-V. Differences were also found in waves I and III in the group ≥ 45 years, compared with the younger age group taken as a reference (Table II).

Discussion

The findings of this study show the differences between men and women according to the age groups constructed. Differences in latency times were observed in all age groups, mainly in the groups of 25-34 years and 35-44 years, for waves III and V and intervals I-III and IV, similar to results reported by Michalewsky et al. and Houston et al.^13,14

Sex differences were observed in all age groups, women having shorter latencies compared to men. As for these differences, Stochard et al. reported that women had shorter latencies compared to men; this feature was attributed to the fact that women have shorter auditory pathway segments because the size of their brains is smaller, with reference to cephalic perimeter measurements.³ These results have been replicated in several reports,^14-17 although the origin of these differences are not fully known. A possible anatomical explanation is that women have a smaller head size compared to men;^3,14 however, some reports have shown that men have longer latencies compared with women with a similar cephalic diameter.¹⁷ So, other factors must influence these differences. Some authors have evaluated the role of sex hormones in the auditory pathway. Elkind-Hirsch et al. found an increase in waves III and V and in the I-V interpeak interval associated with the hyperestrogenic state in healthy women with normal menstrual cycles.¹⁸ Recent evidence has demonstrated the presence of estrogen receptors (ER-alpha and ER-beta) in the human inner ear, including type 1 spiral ganglion cells, the stria vascularis, and cochlear blood vessels. Theoretically, estrogen can affect auditory function at different levels within the central nervous system (CNS) as a modulator of GABAergic, serotonergic, and glutamatergic systems.¹⁹ In our study, the levels of estrogen and head circumference were not measured or correlated.  

While differences were found in most latencies as age increased, these were not significant, probably due to fewer participants in the older group. Some studies have documented differences by age- mainly between child and adult populations- related to CNS development;¹⁴ some other reports have found longer latencies in older adults,²⁰ while others have not.²¹ Some reports have found a significant increase due to age in wave III and a minor effect on the other waves and intervals.^17,22 The results found in our study showed an effect on the latency of waves I and V as participant age increased, suggesting peripheral auditory changes at the midbrain level with age. Also, wave V showed a greater difference in latency between the sexes (Figures 1 and 2) (Table I). 

Hypoglycemia has been linked to an increase in latencies of III-V and I-V intervals.³ However, statistical analysis was done to rule out BAEP modifications due to higher than normal glucose levels but no significant differences were found. 

Multiple regression models included all demographic variables, in addition to laboratory results and BAEP. The variables with high R2 and the largest beta coefficient were age and sex.

In this regard, it was found that for all latencies of waves and intervals, men tend to have longer latency times. In terms of age, only waves I and III had a positive correlation with increasing age. Trune et al. reported similar results using linear regression models.¹⁷ In addition, Mitchell et al. conducted a simple regression model adjusted for age and found a positive correlation between the latter and the latencies of the waves, as well as longer latencies in men.²⁰

One of the main causes of occupational hearing loss is noise exposure, together with organic solvents,^23-25 ​​which affect the central auditory pathway.^25,26 While most human studies have used audiometry as a method of assessing the damage caused by organic solvents, few studies have explored the effects these substances incur at the central level.²⁷ In addition, there is no consensus for assessing simultaneous exposure to noise and organic solvents, or hearing impairment prevention programs or surveillance of populations at risk.²⁸ Therefore, it is important to establish a battery of tests to fully assess hearing damage, with BAEP a possible tool for this purpose.  

The limitations of this study include its retrospective nature, and the lack of measurements of participant head circumference, which may have been correlated with average times of waves and intervals. In addition, the exclusion of subjects over 65 and the small number of participants in the category ≥ 45 years probably contributed to the differences between younger and older people being minimal.

Since the population was not selected randomly and is not representative of the adult population insured by IMSS, the results lack external validity for use as reference values ​​in other studies; however, because measurement errors and the effect of confounding variables were controlled, the results have internal validity for our research purposes as ​​useful reference values for audiological studies we conduct, including BAEP evaluation.

Conclusions

This study determined the average latencies of waves and intervals of BAEPs in a sample of Mexican adults.

According to multiple linear regression models, age and sex were the variables with the greatest statistical power to explain the differences in latencies of this population. This research also contributes to consolidating the evidence for the standardization of BAEP, emphasizing the importance of generating reference values ​​and reliable standards for testing BAEP, in order to use this diagnostic tool in healthy populations and those at risk of hearing pathologies.

Acknowledgements

To all participants who contributed to this study and to the CMN SXXI Blood Bank staff who worked with us.

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