Natl. J. Physiol. Pharm. Pharmacol. (2025), Vol. 15(2): 187-192

Original Research

10.5455/NJPPP.2025.v15.i2.12

Evaluation of Brainstem Auditory Evoked Potentials in migraine patients during interictal phase: An observational cross-sectional study

Daniya Khalid¹*, Jyotsna Shukla¹ and Rajni Fulwariya²

¹Department of Physiology, SMS Medical College and Attached Hospitals, Jaipur, India²Department of Neurology, SMS Medical College and Attached Hospitals, Jaipur, India

*Corresponding Author: Daniya Khalid. Department of Physiology, SMS Medical College and Attached Hospitals, Jaipur, India. Email: daniyakhalid6893 [at] gmail.com

Submitted: 07/11/2024 Accepted: 31/01/2025 Published: 28/02/2025

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Abstract

Background: Migraine, the second most common type of primary headache disorder, is a complex neurological syndrome exhibiting a cyclical pattern. The attacks are frequently associated with phonophobia predisposing patients to inflammatory auditory damage. Therefore, they remain hypersensitive to sound even during the headache-free period. Frequent attacks increase the risk of otologic comorbidities early in life. Brainstem Auditory Evoked Potential (BAEP), one of the most sensitive electrophysiological tests of central nervous system (CNS) dysfunction, was selected for this study to identify signal conduction defects within the auditory pathway up to brainstem projections during the interictal phase.

Objective: This study aimed to evaluate Brainstem Auditory Evoked Potentials in terms of wave absolute latencies and interpeak latencies among migraine patients and compare them to healthy matched controls.

Materials and methods: This comparative, cross-sectional study was performed in the Physiology Department of SMS Medical College, Jaipur, Rajasthan, between April 2023 and June 2024 using click stimuli with rarefaction polarity. Seventy consenting participants, aged 20–40 years of both genders were divided into case and control groups, comprising of diagnosed migraine patients during the interictal phase recruited from the Neurology OPD, SMS hospital, Jaipur, and age and gender-matched healthy employees of SMS medical college, Jaipur, respectively. The brainstem potentials in terms of wave absolute and interpeak latencies were recorded at 60 dB above the sensation level (SL) binaurally. Data were analyzed using the unpaired Student’s t-test.

Results: Migraineurs exhibited significantly longer absolute latencies of wave III and wave V as well as inter-peak latencies of waves I-V and III-V (p < 0.05) during the interictal phase compared to age- and gender-matched healthy controls. However, no significant differences were observed between the case and control groups regarding Wave I parameters.

Conclusion: We concluded that the extent of inflammatory insult to auditory neurons causing signal conduction deficit is more pronounced within the central than the peripheral auditory pathway. BAEP test promises to be an efficient tool to detect neural abnormalities during the interictal phase within the subcortical auditory pathway before the signs and symptoms of impaired hearing manifest.

Keywords: Brainstem, Evoked Response, Migraine disorders, Headache, Hearing loss.

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Introduction

Migraine is one of the most prevalent forms of Headache Disorders affecting over 1 billion individuals globally (Ashina et al., 2021). The disease exhibits a cyclical pattern with a period of complete freedom from pain between the attacks, known as the interictal phase (Burch et al., 2019). Across all age groups and both sexes, it is the second most common cause of disability (Vos et al., 2020). Ictal pain as well as psycho-somatic interictal afflictions cause significant paralysis of the socio-personal, scholastic, and financial spheres of life (Vincent et al., 2022).

Migraineurs with a high attack recurrence rate are more prone to neuro-otologic debilitations (Kayan and Hood, 1984). During the interictal phase, a spontaneous wave of gradual depolarization called cortical spreading depression occurs prior to the activation of trigeminal afferents. This triggers neurovascular inflammation and release of mediators (Wahl et al., 1994), such as substance P, calcitonin gene-related peptide, and neurokinin A, from the vascular endothelia and perivascular nerves, culminating in acute pain (De Tommaso et al., 2014). Recurrent episodes of inflammation during attacks cause cytokine accumulation, which damages the neural membrane and impairs the functionality of neurons involved in auditory signal conduction. Hence, inter-dependence exists between sensorineural hearing impairment and intracranial neurovascular hyper-response due to the release of inflammatory neuro-peptides.

The attack manifests as moderate to severe pulsating, unilateral headache that lasts for 4–72 hours and patients experience an array of autonomic, cognitive, emotional, and sensorimotor symptoms (Goadsby et al., 2017; Pescador Ruschel and De Jesus, 2024). Seventy to ninety percent of these patients exhibit noise aversion during the attack episodes and remain hypersensitive to acoustic stimuli even after the attack. This phenomenon arises from the atypical activation of auditory neural networks (De Tommaso et al., 2014), which lowers the sound discomfort threshold during the interictal phase (Main et al., 1997; Vingen et al., 1998; Ashkenazi et al., 2009).

Previous visual and auditory evoked potential studies have demonstrated the presence of defective sensory information processing at the cortical level during the pain-free period (Kennard et al., 1978; Drake et al., 1990). This altered synchronicity of auditory neural firing occurs not just at the cortical but also subcortical level (De Tommaso et al., 2014). However, recordings of Brainstem Auditory Evoked Potentials among migraine patients have yielded contradictory results (Sand and Vingen, 2000; Dash et al., 2008; Hamed et al., 2012).

Brainstem Evoked Response Audiometry (BERA) is an objective noninvasive electrophysiological test with 70–90% sensitivity and specificity (Balasubramanian, 2015), making it highly suitable for studying any functional abnormalities within subcortical structures involved in processing auditory information and signal conduction up to brainstem nuclei throughout the disease cycle.

This study was conducted among migraine patients during the interictal phase to elucidate the involvement of auditory brainstem structures for risk assessment of otologic morbidity. The location and extent of damage to the auditory pathway were determined by analyzing the response of auditory neuronal components to external acoustic stimuli up to brainstem nuclei using wave absolute and interpeak latencies. This will facilitate the detection of even mild subclinical auditory involvement and will aid in the incorporation of prophylactic interventions at the earliest.

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Materials and Methods

The present study was a hospital-based, comparative, cross-sectional type of observational study conducted at the Physiology Department of S.M.S Medical College, Jaipur (Rajasthan) from April 2023 to June 2024 after receiving the desired approval from the Research Review Board and the Institutional Ethics Committee (Order no. 718/MC/EC/2023, 12/03/2023). A total of 70 study participants were recruited within the age group of 20–40 years from both genders after obtaining the written informed consent. The procedure was explained to all before commencing any test and a detailed history was recorded.

Inclusion criteria

Diagnosed case of migraine (Headache Classification Committee of the International Headache Society (IHS), 2013) during the interictal phase and age- and gender-matched healthy employees who were cooperative and willing to participate in the study.

Exclusion criteria

Participants with any history of other neurological, otologic, psychiatric, and acute or chronic medical illnesses, migraine patients during the ictal and immediate post-ictal phases, pregnant and lactating women, chronic alcoholics, and smokers were excluded from the study.

A sample size of 35 in each group was calculated for the study purpose, using MedCalc 16.2 software at a 95% confidence level (α error=0.05) and 80% power, as a previous study (Kalita et al., 2021) showed a minimum detectable difference (BERA wave II at 40 dB sensation level [SL]) in the mean of 0.09 µV and SD of 0.13 µV between the migraine patients and the healthy control group.

The participants were 35 migraine patients from Neurology OPD, SMS Hospital, Jaipur (Rajasthan) during the headache-free period and 35 age- and sex-matched healthy employees of SMS Medical College, Jaipur (Rajasthan) comprising case and control groups, respectively.

Baseline anthropometric parameters, such as height, weight, and Body Mass Index (BMI), were recorded. All participants were subjected to clinical aural examination as well as subjective audiometric tests to rule out conductive disorders and any overt hearing impairment. BERA was performed to evaluate the responses of auditory neurons involved in signal conduction and compare them between migraineurs and their matched healthy counterparts. The parameters assessed were the absolute latencies and interpeak latencies of Waves I, III, and V, the clinically most significant waves (Chiappa and Ropper, 1982).

The test was conducted with an RMS EMG SALUS–2C machine in the laboratory of the Physiology Department at SMS Medical College, Jaipur (Rajasthan). All selected candidates were instructed to refrain from applying hair oil or gel to minimize interference during recordings using silver chloride cup electrodes connected to the Pre-Amp. The electrodes were affixed to the scalp as follows: Reference electrode at the vertex (Cz), Ground electrode over the forehead (Fz), and Active electrodes over the mastoid processes (left mastoid – A1, right mastoid – A2) (Wikipedia Contributors, 2024). The impedance was kept below 5 kOhms for all electrodes.

The click sound stimuli of rarefaction polarity were delivered monaurally using supra-aural headphones at 60 dB above the SL at a rate of 10/second while the contralateral ear was masked with white noise at 30 dB below the stimulus intensity for better response (Jewett and Williston, 1971). The ipsilateral stimulation-derivation technique was used for recording the absolute latencies of Waves I, III, and V and interpeak latencies of Waves I-III, III-V, and I-V from both ears. Responses were live averaged for 1,000 stimuli and analyzed in side-specific manner.

All data were quantitative and expressed as mean ± SD. The results for both ears were statistically analyzed using “SPSS software” version 25 and compared between the case and control groups with respect to wave absolute latencies and interpeak latencies by applying the two-tailed Unpaired Student’s “t” Test. The significance level was assigned at a p-value < 0.05.

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Results

Table 1 presents the baseline anthropometric characteristics of migraine patients and healthy controls. The mean ages of the participants in the case and control groups were 31.6 ± 6.27 and 31 ± 6.11, respectively. In our study, the proportions of female and male migraine patients were 62.8% and 37.2%, respectively. There were no significant differences in age, height, weight, and BMI between the groups.

A significantly prolonged Wave III and Wave V absolute latencies (p-value < 0.05) for the left ear (Table 2) as well as the right ear (Table 3) among migraine patients was observed, while Wave I latency failed to show any significant difference (p-value > 0.05) binaurally when compared to matched healthy controls at 60 dB SL.

The interpeak latencies that represent signal conduction between different stations of the auditory pathway showed significantly prolonged Wave III-V and Wave I-V inter-peak latencies (IPLs) at 60 dB SL for the left ear (Table 2) as well as for the right ear (Table 3) among migraine patients during headache-free period compared with controls. IPL of Wave I-III was prolonged among cases in both ears but the difference was insignificant compared with healthy controls.

Table 1. Baseline characteristics of migraine patients and control groups (mean ± SD).

Table 2. Comparison of wave latencies (mean ± SD) between migraine patients and control groups: left ear.

Table 3. Comparison of wave latencies (mean ± SD) between migraine and control groups: right ear.

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Discussion

This study assessed the responses of structures involved in auditory signal conduction up to the brainstem level among migraine patients during the interictal period to detect any subclinical dysfunction.

There was no statistically significant difference in age, sex, and BMI between the case and control groups, ruling out the effect of confounding variables.

From stimulus presentation to response generation, the duration of an auditory impulse to traverse the brain pathway is represented as absolute wave latencies. The absolute latencies of waves I, III, and V are indicative of the neural integrity of the 8th cranial nerve, neural conduction up to the cochlear nucleus, and up to brainstem nuclei (lateral lemniscus), respectively.

This study revealed significantly prolonged absolute latencies of waves III and V among migraine patients at 60 dB SL binaurally, indicating delays in signal conduction within the auditory pathway. Schlake et al. (1990) recorded longer absolute latencies for all waves among migraineurs using similar stimulus conditions but the results were not statistically significant.

Yang et al. (2000), Bayazit et al. (2001), Dash et al. (2008), and Sowmiya and Vinodha (2015) found that migraineurs have significantly longer absolute latencies of waves III and V, which is consistent with our findings. Their recordings, however, also exhibited significantly longer wave I latencies, emphasizing cochlear defects along with central affections, which contrasts with our study where no significant difference in wave I latencies was found. This discrepancy could be attributed to the patient recruitment pattern since prior studies examined cases during ictal as well as interictal periods, our study included patients only during the interictal phase.

Our study findings are consistent with those of Sand et al. (2008), who recorded the BAEP parameters of migraine patients during the pre-attack, attack, and post-attack periods. During the interval period following attack episodes, significantly longer absolute latencies of waves III and V were demonstrated. However, our findings on Wave V latencies are entirely at odds with those recorded by Firat et al. (2006), Gopal et al. (2007), and Vijayalakshmi et al. (2016) because they failed to notice any significant difference between the case and control groups.

Trigeminovascular nociceptive activation with dysfunction of Central nervous system (CNS) structures involved in pain modulation manifests as attack paroxysms, whereas recurrence is a result of repetitive insults and sensitization leading to sequential intracranial structural and functional alterations (Noseda and Burstein, 2013; Goadsby et al., 2017).

A central auditory dysfunction mostly presents with prolonged IPL of wave I-V. Longer IPL of wave I-III indicates auditory nerve or cochlear pathology while that of wave III-V indicate pathology above the level of the cochlea up to the medulla oblongata and pons (Young et al., 2024).

In a cross-sectional study conducted by Bayazit et al. (2001), 20% of patients exhibited normal IPLs, while 15% showed prolonged IPLs compared to standard normative data. Hence, their results were inconclusive. Similarly, Firat et al. (2006) showed prolonged wave I-V IPL during the asymptomatic period but the difference was insignificant.

Dash et al. (2008) and Sowmiya and Vinodha (2015) reported prolonged IPLs compared with healthy controls, marking them to be the earliest indicator of impending auditory involvement in migraine. However, they also reported prolonged Wave I-III IPL, which does not match our study’s results in which no significant difference was found between the patient and control groups. This might be due to the difference in the selection criteria since participants with any clinical or subjective hearing impairment were excluded from this study.

Our study recorded a significantly prolonged IPL wave III-V and wave I-V at 60 dB SL for both ears among migraine patients during the headache-free period compared to controls. These results are in line with the studies performed by Drake et al. (1990) at 70 dB SL who recorded longer IPL wave I-V and III-V (Drake et al., 1990). Yang et al. (2000) and Sand et al. (2008) observed significantly prolonged IPL wave III-V. Hamed et al. (2012) reported a notably longer IPL for wave I-V among migraine patients at 90 dB, while Xue et al. (2020) found similar results at 80 dB. These findings regarding the IPL of waves III-V and I-V closely resemble our results.

The outcome of the study by Zhang et al. (2020) showed central pathway damage beyond eight cranial nerves, which is in concordance with the results of this study. However, according to a study conducted by Albanese et al. (2021), the damage to auditory neural pathways was peripheral (cochlear). When Hamed et al. (2012) and Xue et al. (2020) performed otoacoustic emissions along with BERA studies, they concluded the presence of both peripheral and central damage among migraineurs. These findings do not support our results because wave I latency as well as IPL wave I-III were not significantly prolonged.

Limitation(s)

This study had a small sample size and a cross-sectional design which cannot be used to establish a direct cause-effect relationship between migraine attacks and otologic damage. In addition, the patients were not segregated on the basis of treatment received and disease duration. Since, these can impact the ongoing auditory neural damage and, thereby, the final results, they should be considered in future studies.

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Conclusion

The rise in the prevalence of sensorineural hearing impairment among migraine patients poses a serious risk of otologic morbidities early in life. BAEP recordings can provide better insight into the disrupted processing of sensory information from the cochlea up to the brainstem among patients and identify any functional anomalies within structures related to auditory signal transmission. This study emphasizes the importance of including preventative measures during the asymptomatic phase into patients’ treatment regimens while also ensuring strict patient compliance. Therefore, BAEP testing can facilitate the early diagnosis of mild subclinical auditory damage and help monitor patient responses to various interventions over time.

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Acknowledgments

We would extend our thanks to the Neurology Department of SMS Medical College and Hospital for their continuous support.

Ethical approval

The Institutional Research Review Board approved this study.

Conflict of interest

The authors declare no conflicts of interest.

Funding

Nil.

Author’s contribution

Dr. Daniya Khalid: Study design, Literature analysis, Data collection, Data analysis, and Manuscript preparation. Dr. Jyotsna Shukla: Idea of research, Concepts, and Preparing the first draft of the manuscript. Dr. Rajni Fulwariya: Data acquisition and Manuscript review.

Data availability

The data supporting the findings and results of this study are available from the corresponding author upon request.

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