1.1

Aim of work

The aim of this study was to objectively assess the functions of cochlea and peripheral and central auditory pathways in a group of patients with migraine using routine diagnostic audiometry along with evoked otoacoustic emissions [EOAEs, transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emission (DPOAEs)] and ABR testing. Otoacoustic emissions are sensitive objective methods to assess cochlear function and monitor dynamic changes in cochlear responsiveness before functional and significant hearing loss occurs from any cause .

2.1

Patients

This study included 58 adults with migraine and 40 healthy subjects matched for age, sex, socioeconomic status, and educational level as controls for comparison. Headache was classified according to the criteria of the International Headache Society (second edition) . Patients were studied during the attack-free periods with at least 3 days since the last attack. Patients were recruited from the outpatient headache clinic of Assiut University Hospital, Assiut, Egypt. The protocol of the study was approved by the ethical committee of Assiut University, and subjects included gave informed consents before participation. Excluded were subjects with previous history of otological or labyrinthine disorders, systemic or metabolic diseases associated with hearing loss (eg, renal insufficiency, gout, diabetes mellitus, hypertension, hypercholesterolemia/dyslipidemia, hypothyroidism, or active gastrointestinal disease), reported exposure to unsafe noise, use of ototoxic drugs, family history of hearing loss, or clinical evidence of postural hypotension.

2.2

Methods

All patients and control subjects went through full neurological, medical, and audiological history and examination. The frequency of migraine attacks was monitored per month. Accordingly, patients were divided into 2 groups: ( a ) patients with high frequency attaches: those with at least 4/month and ( b ) patients with low frequency attacks: those with less than 4/month. All participants underwent basic audiological evaluation that included initial otoscopic examination, standard pure tone audiometry (PTA), speech audiometry, tympanometry, and acoustic reflex to exclude pathologic conditions of the external or middle ear. Speech audiometry was used to identify the hearing level (HL) at which subjects understood and repeated at least 90% of a set of 10 monosyllables. Immittance testing was done to determine middle ear function using the Amplaid Model 720 immittance bridge (Amplaid, Milan, Italy). Pure tone audiometric thresholds were measured from 0.25 to 8 kHz (0.25, 0.5, 1.0, 2.0, 4.0, and 8.0 kHz), and pure average thresholds for the right and left ears were obtained (Model AC40, version 1.28; Interacoustics, Assens, Denmark). Hearing thresholds were determined in decibel (dB) HL. The examined ears were defined as normal if no absolute threshold level greater than 20 dB was measured over the whole frequency range. Threshold shifts in PTA were considered to be significant if they showed at least 10 dB change in more than 2 consecutive frequencies or if a threshold greater than 20 dB was observed in any audiometric range.

In the same session, TEOAEs and DPOAEs were recorded and analyzed. The TEOAEs were recorded using a commercially available system (ILO88, version 4.2; Otodynamic Ltd, Hatfield, UK). Applied stimuli were rectangular clicks with a duration of 80 microseconds presented at an overall rate of 50/s at a peak sound pressure level (SPL) of 82 dB (±2 dB) using the nonlinear mode. Starting 5 milliseconds after stimulation, 260 responses were amplified, filtered by band passing (0.5–6 kHz), and averaged within a time window of 20 seconds to generate a mean echo response. The noise rejection level was set at the default level of 45 dB SPL. The TEOAEs were considered present when stimulus stability was better than 80% with response reproducibility of more than 50%. The typical noise floor was −12 dB. TEOAEs’ global and band response levels (1.0, 1.4, 2.0, 2.8, and 4.0 kHz) were compared between patients and controls. DPOAEs were recorded using computer-based ILO92 (version 1.2; Otodynamic Ltd). Two simultaneous pure tone signals (primaries) were presented to the ear at 2 different frequencies (f1 and f2, where f1 < f2), and 2f1-f2 cubic distortion-product component was recorded. The 2 stimuli were mixed acoustically and delivered to a probe. The DPOAE amplitude as a function of f2 frequency at a fixed stimulus level (distortion product frequency profiles or DP-grams) was collected. DP-gram recordings were obtained with a frequency ratio f2/f1 fixed at 1.22. Nine pairs of equal level primary frequencies (L1 = L2 = 70 dB SPL) were used at 3 points per octave, spanning f2 frequency range from 1001 to 6006. The 70-dB level of the primary tones was used as this stimulus level most reliably elicits DPOAEs from ears with hearing difficulties. The primary levels of the 2 stimulus tones (f1 and f2) are related by the formula L1 = 39 dB + 0.4 × L2 (up to an L2 of 70 dB SPL) . The DP-gram amplitude across the entire frequency range was determined for each patient. The measurements were done in 2 points per octave from 1- to 6-kHz distortion product. Detection threshold was calculated 3 dB above the noise floor. The ILO92 system performs a statistical test on the noise in the 2f1-f2 frequency area, and only DPOAEs with amplitudes greater than 2 standard deviations above the noise floor were considered valid.

ABR recording was done by a Nicolet Spirit evoked potential system OS/2 version 3 (Nicolet, Madison, WI). Auditory brainstem response was performed using alternating clicks at 0.1 second, time window was 10 milliseconds, and filter settings were 150 Hz to 3 kHz. The stimuli were delivered at 90 dB HL with repetition rate of 11.1 to 51.1 pulses per second. Each response reflected an average of 1500 stimuli presentations. The absolute latencies of waves I, III, and V and I-III, III-V and I-V IPLs were recorded from both ears.

2.1

Patients

This study included 58 adults with migraine and 40 healthy subjects matched for age, sex, socioeconomic status, and educational level as controls for comparison. Headache was classified according to the criteria of the International Headache Society (second edition) . Patients were studied during the attack-free periods with at least 3 days since the last attack. Patients were recruited from the outpatient headache clinic of Assiut University Hospital, Assiut, Egypt. The protocol of the study was approved by the ethical committee of Assiut University, and subjects included gave informed consents before participation. Excluded were subjects with previous history of otological or labyrinthine disorders, systemic or metabolic diseases associated with hearing loss (eg, renal insufficiency, gout, diabetes mellitus, hypertension, hypercholesterolemia/dyslipidemia, hypothyroidism, or active gastrointestinal disease), reported exposure to unsafe noise, use of ototoxic drugs, family history of hearing loss, or clinical evidence of postural hypotension.

2.2

Methods

All patients and control subjects went through full neurological, medical, and audiological history and examination. The frequency of migraine attacks was monitored per month. Accordingly, patients were divided into 2 groups: ( a ) patients with high frequency attaches: those with at least 4/month and ( b ) patients with low frequency attacks: those with less than 4/month. All participants underwent basic audiological evaluation that included initial otoscopic examination, standard pure tone audiometry (PTA), speech audiometry, tympanometry, and acoustic reflex to exclude pathologic conditions of the external or middle ear. Speech audiometry was used to identify the hearing level (HL) at which subjects understood and repeated at least 90% of a set of 10 monosyllables. Immittance testing was done to determine middle ear function using the Amplaid Model 720 immittance bridge (Amplaid, Milan, Italy). Pure tone audiometric thresholds were measured from 0.25 to 8 kHz (0.25, 0.5, 1.0, 2.0, 4.0, and 8.0 kHz), and pure average thresholds for the right and left ears were obtained (Model AC40, version 1.28; Interacoustics, Assens, Denmark). Hearing thresholds were determined in decibel (dB) HL. The examined ears were defined as normal if no absolute threshold level greater than 20 dB was measured over the whole frequency range. Threshold shifts in PTA were considered to be significant if they showed at least 10 dB change in more than 2 consecutive frequencies or if a threshold greater than 20 dB was observed in any audiometric range.

In the same session, TEOAEs and DPOAEs were recorded and analyzed. The TEOAEs were recorded using a commercially available system (ILO88, version 4.2; Otodynamic Ltd, Hatfield, UK). Applied stimuli were rectangular clicks with a duration of 80 microseconds presented at an overall rate of 50/s at a peak sound pressure level (SPL) of 82 dB (±2 dB) using the nonlinear mode. Starting 5 milliseconds after stimulation, 260 responses were amplified, filtered by band passing (0.5–6 kHz), and averaged within a time window of 20 seconds to generate a mean echo response. The noise rejection level was set at the default level of 45 dB SPL. The TEOAEs were considered present when stimulus stability was better than 80% with response reproducibility of more than 50%. The typical noise floor was −12 dB. TEOAEs’ global and band response levels (1.0, 1.4, 2.0, 2.8, and 4.0 kHz) were compared between patients and controls. DPOAEs were recorded using computer-based ILO92 (version 1.2; Otodynamic Ltd). Two simultaneous pure tone signals (primaries) were presented to the ear at 2 different frequencies (f1 and f2, where f1 < f2), and 2f1-f2 cubic distortion-product component was recorded. The 2 stimuli were mixed acoustically and delivered to a probe. The DPOAE amplitude as a function of f2 frequency at a fixed stimulus level (distortion product frequency profiles or DP-grams) was collected. DP-gram recordings were obtained with a frequency ratio f2/f1 fixed at 1.22. Nine pairs of equal level primary frequencies (L1 = L2 = 70 dB SPL) were used at 3 points per octave, spanning f2 frequency range from 1001 to 6006. The 70-dB level of the primary tones was used as this stimulus level most reliably elicits DPOAEs from ears with hearing difficulties. The primary levels of the 2 stimulus tones (f1 and f2) are related by the formula L1 = 39 dB + 0.4 × L2 (up to an L2 of 70 dB SPL) . The DP-gram amplitude across the entire frequency range was determined for each patient. The measurements were done in 2 points per octave from 1- to 6-kHz distortion product. Detection threshold was calculated 3 dB above the noise floor. The ILO92 system performs a statistical test on the noise in the 2f1-f2 frequency area, and only DPOAEs with amplitudes greater than 2 standard deviations above the noise floor were considered valid.

ABR recording was done by a Nicolet Spirit evoked potential system OS/2 version 3 (Nicolet, Madison, WI). Auditory brainstem response was performed using alternating clicks at 0.1 second, time window was 10 milliseconds, and filter settings were 150 Hz to 3 kHz. The stimuli were delivered at 90 dB HL with repetition rate of 11.1 to 51.1 pulses per second. Each response reflected an average of 1500 stimuli presentations. The absolute latencies of waves I, III, and V and I-III, III-V and I-V IPLs were recorded from both ears.