PMC:4630263 / 5622-13698 JSONTXT

{"project":"TEST0","denotations":[{"id":"26527349-119-125-1499009","span":{"begin":327,"end":329},"obj":"[\"20591729\", \"20601917\"]"},{"id":"26527349-61-67-1499010","span":{"begin":4668,"end":4670},"obj":"[\"16481825\"]"},{"id":"26527349-160-165-1499011","span":{"begin":6848,"end":6849},"obj":"[\"20080441\"]"},{"id":"26527349-223-229-1499012","span":{"begin":7288,"end":7290},"obj":"[\"21305862\"]"}],"text":"Methods\n\nSubjects\nThis study collected data obtained from consecutive first-visit patients with migraine without aura and episodic TTH treated in the neurology outpatient department of a university hospital. All participants were between 20 and 60 years of age, and only females were included to eliminate age and gender bias [24–26]. Headache diagnoses were classified by a board-certified neurologist based on the criteria of the International Classification of Headache Disorders-3 beta version (ICHD-3β) using patient history, a neurological examination, and laboratory or neuroimaging studies. To exclude other primary headaches, patients were required to have at least a 1-year history of migraine or TTH headaches prior to enrollment. Patients who had auras or vestibular symptoms during headache attacks were excluded. In total, 38 patients with migraine without aura and 30 patients with episodic TTH based on the ICHD-3β were enrolled in the study. Subjects with episodic TTH were defined as those with headaches lasting from 1 to 15 days per month (frequent episodic TTH). The control group consisted of age-matched volunteers. We recruited the control group by inviting persons who accompanied the patients to join the study (e.g., friends) and also through advertisements (e.g., posted notices in the hospital). Controls were free of headaches for at least three months prior to the study, experienced no more than an occasional mild headache (\u003c5 times per year) and had not sought medical treatment for headaches.\nAll participants were underwent physical and neurological examinations performed by an experienced neurologist. Participants were asked to complete a questionnaire regarding their headache symptoms, including frequency, duration, and intensity, during the previous 4 weeks. Headache frequency (days/week) was calculated by dividing the number of days with headaches by 4 weeks. Headache duration (hours/day) was calculated by dividing the sum of the total hours of headaches by the number of days with headaches and headache intensity (numeric rating scale [NRS]: 0 = no pain to 10 = unbearable pain) was calculated as the mean NRS for days with headaches. We also obtained a comprehensive neuro-otological history from all participants. The detailed interview for assessing vestibular symptoms in headache patients or diagnosing VM according to the ICHD-3β included questions about clinical features (e.g., main type of vertigo and duration, frequency, severity) and concomitant symptoms. Exclusion criteria included subjects with hearing loss, middle ear disease or surgery, history of vestibular disease, history of recurrent vertigo or vertigo that lasted more than one day or required hospitalization, a cervical disorder that affected head movement, the presence of neurological disorders (e.g. stroke, multiple sclerosis), pregnancy, daily medication to prevent headaches and/or antidepressant medication, medication-overuse headache, and patients with VM.\nWritten informed consent was obtained from all subjects prior to enrollment. The university hospital ethics committee approved this study.\n\nVEMP recordings\nVEMP tests were performed by an examiner blinded to group and patient clinical examination data. VEMP recordings were performed using a Nicolet EDX EMP/EP machine (Natus Neurology, Middleton, WI, USA). Patients with headache underwent VEMP testing on headache-free days. Specifically, recordings in migraine patients were obtained interictally at least 3 days after the last and before the next migraine attack.\n\noVEMP\nFor oVEMP testing, the active electrode was placed ~1 cm below the center of the inferior eyelid contralateral to the sound stimulation, with the reference electrode located 15 mm below the active electrode and the ground electrode on the forehead. Patients were tested in a seated position. During the test, patients were asked to look upward to a fixed point 2 m away and 25-30° above the horizontal line. Electromyography (EMG) signals were amplified and band pass-filtered between 30 and 3000 Hz. Sound stimuli were presented through headphones as short tone burst sounds (500 Hz) at a frequency of 5 Hz. In total, 100 stimuli were applied to each ear and repeated twice consecutively at 130 dB normal hearing level (nHL).\n\ncVEMP\nFor cVEMP testing, the active electrode was placed on the upper one-third of the sternocleidomastoid (SCM) muscle, ipsilateral to the sound stimulation, with the reference electrode on the anterior margin of the clavicle and the ground electrode on the forehead. Patients were tested in a seated position. To contract the SCM, we used the blood pressure cuff method [27]. Subjects had to flex the head ~30° forward and rotate it ~30° to the opposite side. While holding the cuff between the right hand and jaw, the subject pushed with her head against the hand-held cuff to generate a cuff pressure of 40 mmHg. The obtained cuff pressures and background muscle activity based on visual feedback system of the VEMP machine were monitored by the subject and investigator during the recording period. EMG signals were amplified and band pass-filtered between 20 and 2000 Hz. Sound stimuli (500 Hz) were presented through headphones as rarefaction clicks 0.1 ms in duration and at a frequency of 5 Hz. In total, 128 stimuli were applied to each ear and repeated twice consecutively at a 125 dB nHL.\n\nVEMP analysis\nFrom the oVEMP graphs, unrectified signals from 100 trials were averaged. The first negative and positive responses were designated as n1 and p1 waves, respectively. The oVEMP response was only considered reliable if the n1 and p1 peaks were reproducible in two consecutive trace runs. Additionally, the cVEMP response was only considered reliable if the p13 and n23 peaks were reproducible in two consecutive runs of the unrectified trace. The p13-n23 responses were observed best in the unrectified trace. Initial positive and negative polarities of the waveform with peaks were termed p13 and n23 on the basis of their respective latencies. Rectified values were used since the VEMP response amplitude is significantly affected by the force of muscular contraction or stimulus intensity. After rectification (Synergy Reader software, version 20.1), peak latencies of p13 and n23 and amplitude parameters p13 and n23 were measured. The results of both runs were averaged, providing the final response from which the peak-to-peak amplitude (n1-p1) and absolute latencies (n1, p1) in oVEMP and rectified amplitude and absolute latencies (p13, n23) in cVEMP were derived. Interside differences of n1 and p1 latencies in oVEMP and p13 and n23 latencies in cVEMP were calculated. Amplitude asymmetry ratio (AR) was calculated in oVEMP and cVEMP as follows: (larger response - smaller response) / (larger response + smaller response) × 100 [4].\n\nStatistical analyses\nStatistical analyses were performed using ‘R’ (version 3.01; R Foundation for Statistical Computing, Vienna, Austria) and P-values \u003c0.05 were considered to indicate statistical significance. The planned sample of 38 migraineurs and 46 healthy subjects resulted in a power of 90 % for detecting a 40 % reduction in the bilateral oVEMP response at a significance level of 0.05 using a two-sided Fisher’s exact test [16]. Additionally, the sample size calculation for the t-test to detect the difference in N1 latencies between the migraine and healthy control groups required 24 and 48 subjects, respectively. Data were expressed as the means ± standard deviation (SD) for continuous variables and as numbers (rates) for categorical variables. Continuous variables were compared using a two-sample t-test or Wilcoxon’s rank sum test, whereas categorical variables were evaluated using the χ2 test or Fisher’s exact test. Results of oVEMP and cVEMP parameters were compared among three subgroups. Multiple group analyses were performed using one-way analysis of variance (ANOVA) or the Kruskal-Wallis test. Pair-wise comparisons were assessed using the Wilcoxon’s rank sum test with Bonferroni correction."}

{"project":"2_test","denotations":[{"id":"26527349-20591729-60553891","span":{"begin":327,"end":329},"obj":"20591729"},{"id":"26527349-20601917-60553891","span":{"begin":327,"end":329},"obj":"20601917"},{"id":"26527349-16481825-60553892","span":{"begin":4668,"end":4670},"obj":"16481825"},{"id":"26527349-20080441-60553893","span":{"begin":6848,"end":6849},"obj":"20080441"},{"id":"26527349-21305862-60553894","span":{"begin":7288,"end":7290},"obj":"21305862"}],"text":"Methods\n\nSubjects\nThis study collected data obtained from consecutive first-visit patients with migraine without aura and episodic TTH treated in the neurology outpatient department of a university hospital. All participants were between 20 and 60 years of age, and only females were included to eliminate age and gender bias [24–26]. Headache diagnoses were classified by a board-certified neurologist based on the criteria of the International Classification of Headache Disorders-3 beta version (ICHD-3β) using patient history, a neurological examination, and laboratory or neuroimaging studies. To exclude other primary headaches, patients were required to have at least a 1-year history of migraine or TTH headaches prior to enrollment. Patients who had auras or vestibular symptoms during headache attacks were excluded. In total, 38 patients with migraine without aura and 30 patients with episodic TTH based on the ICHD-3β were enrolled in the study. Subjects with episodic TTH were defined as those with headaches lasting from 1 to 15 days per month (frequent episodic TTH). The control group consisted of age-matched volunteers. We recruited the control group by inviting persons who accompanied the patients to join the study (e.g., friends) and also through advertisements (e.g., posted notices in the hospital). Controls were free of headaches for at least three months prior to the study, experienced no more than an occasional mild headache (\u003c5 times per year) and had not sought medical treatment for headaches.\nAll participants were underwent physical and neurological examinations performed by an experienced neurologist. Participants were asked to complete a questionnaire regarding their headache symptoms, including frequency, duration, and intensity, during the previous 4 weeks. Headache frequency (days/week) was calculated by dividing the number of days with headaches by 4 weeks. Headache duration (hours/day) was calculated by dividing the sum of the total hours of headaches by the number of days with headaches and headache intensity (numeric rating scale [NRS]: 0 = no pain to 10 = unbearable pain) was calculated as the mean NRS for days with headaches. We also obtained a comprehensive neuro-otological history from all participants. The detailed interview for assessing vestibular symptoms in headache patients or diagnosing VM according to the ICHD-3β included questions about clinical features (e.g., main type of vertigo and duration, frequency, severity) and concomitant symptoms. Exclusion criteria included subjects with hearing loss, middle ear disease or surgery, history of vestibular disease, history of recurrent vertigo or vertigo that lasted more than one day or required hospitalization, a cervical disorder that affected head movement, the presence of neurological disorders (e.g. stroke, multiple sclerosis), pregnancy, daily medication to prevent headaches and/or antidepressant medication, medication-overuse headache, and patients with VM.\nWritten informed consent was obtained from all subjects prior to enrollment. The university hospital ethics committee approved this study.\n\nVEMP recordings\nVEMP tests were performed by an examiner blinded to group and patient clinical examination data. VEMP recordings were performed using a Nicolet EDX EMP/EP machine (Natus Neurology, Middleton, WI, USA). Patients with headache underwent VEMP testing on headache-free days. Specifically, recordings in migraine patients were obtained interictally at least 3 days after the last and before the next migraine attack.\n\noVEMP\nFor oVEMP testing, the active electrode was placed ~1 cm below the center of the inferior eyelid contralateral to the sound stimulation, with the reference electrode located 15 mm below the active electrode and the ground electrode on the forehead. Patients were tested in a seated position. During the test, patients were asked to look upward to a fixed point 2 m away and 25-30° above the horizontal line. Electromyography (EMG) signals were amplified and band pass-filtered between 30 and 3000 Hz. Sound stimuli were presented through headphones as short tone burst sounds (500 Hz) at a frequency of 5 Hz. In total, 100 stimuli were applied to each ear and repeated twice consecutively at 130 dB normal hearing level (nHL).\n\ncVEMP\nFor cVEMP testing, the active electrode was placed on the upper one-third of the sternocleidomastoid (SCM) muscle, ipsilateral to the sound stimulation, with the reference electrode on the anterior margin of the clavicle and the ground electrode on the forehead. Patients were tested in a seated position. To contract the SCM, we used the blood pressure cuff method [27]. Subjects had to flex the head ~30° forward and rotate it ~30° to the opposite side. While holding the cuff between the right hand and jaw, the subject pushed with her head against the hand-held cuff to generate a cuff pressure of 40 mmHg. The obtained cuff pressures and background muscle activity based on visual feedback system of the VEMP machine were monitored by the subject and investigator during the recording period. EMG signals were amplified and band pass-filtered between 20 and 2000 Hz. Sound stimuli (500 Hz) were presented through headphones as rarefaction clicks 0.1 ms in duration and at a frequency of 5 Hz. In total, 128 stimuli were applied to each ear and repeated twice consecutively at a 125 dB nHL.\n\nVEMP analysis\nFrom the oVEMP graphs, unrectified signals from 100 trials were averaged. The first negative and positive responses were designated as n1 and p1 waves, respectively. The oVEMP response was only considered reliable if the n1 and p1 peaks were reproducible in two consecutive trace runs. Additionally, the cVEMP response was only considered reliable if the p13 and n23 peaks were reproducible in two consecutive runs of the unrectified trace. The p13-n23 responses were observed best in the unrectified trace. Initial positive and negative polarities of the waveform with peaks were termed p13 and n23 on the basis of their respective latencies. Rectified values were used since the VEMP response amplitude is significantly affected by the force of muscular contraction or stimulus intensity. After rectification (Synergy Reader software, version 20.1), peak latencies of p13 and n23 and amplitude parameters p13 and n23 were measured. The results of both runs were averaged, providing the final response from which the peak-to-peak amplitude (n1-p1) and absolute latencies (n1, p1) in oVEMP and rectified amplitude and absolute latencies (p13, n23) in cVEMP were derived. Interside differences of n1 and p1 latencies in oVEMP and p13 and n23 latencies in cVEMP were calculated. Amplitude asymmetry ratio (AR) was calculated in oVEMP and cVEMP as follows: (larger response - smaller response) / (larger response + smaller response) × 100 [4].\n\nStatistical analyses\nStatistical analyses were performed using ‘R’ (version 3.01; R Foundation for Statistical Computing, Vienna, Austria) and P-values \u003c0.05 were considered to indicate statistical significance. The planned sample of 38 migraineurs and 46 healthy subjects resulted in a power of 90 % for detecting a 40 % reduction in the bilateral oVEMP response at a significance level of 0.05 using a two-sided Fisher’s exact test [16]. Additionally, the sample size calculation for the t-test to detect the difference in N1 latencies between the migraine and healthy control groups required 24 and 48 subjects, respectively. Data were expressed as the means ± standard deviation (SD) for continuous variables and as numbers (rates) for categorical variables. Continuous variables were compared using a two-sample t-test or Wilcoxon’s rank sum test, whereas categorical variables were evaluated using the χ2 test or Fisher’s exact test. Results of oVEMP and cVEMP parameters were compared among three subgroups. Multiple group analyses were performed using one-way analysis of variance (ANOVA) or the Kruskal-Wallis test. Pair-wise comparisons were assessed using the Wilcoxon’s rank sum test with Bonferroni correction."}