INTRODUCTION
Patients with migraine commonly show vestibular symptoms1. The International Headache Society (IHS) classification of migraine however refers to vertigo as "migrainous" in adults merely within the frame of basilar migraine2. The relation of vertigo to migraine has been addressed in a number of published case series under diverse names such as, migraine-associated dizziness3, vestibular migraine4, migraine-related vestibulopathy5 and lastly migrainous vertigo6. The peripheral or central vestibular localization of this deficit as well as the pathophysiology is unclear7.
Neurotologic abnormalities in vestibular tests occur in the majority of patients with migraine with or without aura7. Despite the fundamental difference in function between semicircular canal, serving angular motion, and otolith structures, transducing linear motion, diagnostic testing has traditionally involved measurement of horizontal semicircular canal8.
The vestibulospinal reflex (VSR) is an important vestibular system reflex. The VSR, via the lateral vestibulospinal tracts, allows input from the vestibular organs to be used for detection of changes in orientation to gravity and linear forces to the antigravity muscles of the neck (e.g. sternocleidomastoid muscle), thorax, and lower limbs9. The vestibular evoked myogenic potential (VEMP) is a sound-evoked muscle reflex generated from acoustical stimulation of the saccule which lies beneath the stapes footplate and is somewhat sensitive to sound. VEMPs are potentials generated by VSR depending on functional integrity of saccule, inferior vestibular nerve, vestibular nuclei, vestibular-spinal pathways and neuromuscular plates. Damage to any of these structures results in affection of potentials. VEMPs are known as the sacculo-collic (vestibulo-collic) reflex (VCR)10.
Another tool that can assess the VSR is posturography. Computerized dynamic posturography (CDP) assesses the patients' utilization of sensory information: visual input from the environment, proprioception from the feet, and inner ear. The sensory organization test (SOT) measures body sways under modified visual and somatosensory conditions. The SOT can qualitatively assess contributions of the three sensory system inputs for static and dynamic postural sway (equilibrium)8,11.
The aim of this study was to find out the frequency of symptoms of vestibular dysfunction and assess the vestibulo-spinal reflex in migraineurs, in headache free periods, utilizing vestibular evoked myogenic potentials and computerized dynamic posturography.
SUBJECTS AND METHODS
A case-control study included 24 patients with migraine selected from the neurology outpatient clinic at Kasr-El-Eini hospital, Cairo University, Egypt. They were 18 females and 6 males whose ages ranged from 18 to 43 years with a mean of 27.54 ±7.38. Migraine with and without aura was diagnosed according to the diagnostic criteria of the Headache Classification Committee of the International Headache Society4. All patients were assessed in the headache free period. Patients were not on any regular anti-migrainous treatment for at least 3 months prior enrollment in this study. Twenty normal adult volunteers, without history of otologic or vestibular disorders, were enrolled as controls, well-matched as regards age (range 19-49 years with a mean of 28.05±6.89) and gender (16 females and 4 males).
Exclusion criteria : a) The presence of middle or inner ear diseases known to affect hearing or balance, b) Past history of skull, neck trauma, noise exposure or ear surgery, and c) Current or past history of medications known to adversely affect hearing, balance or compensate for balance-related problems.
The studied subjects were submitted to: a) Full history taking (specially symptoms of vestibular or balance dysfunction), b) Clinical assessment: including general, neurological examination including posture tests (Romberg test, tandem stance, gait, tandem gait) and otological examination in addition to examination of eye movements and search for spontaneous or gaze nystagmus, smooth pursuit and saccadic testing, head thrust and head shake test, fixation suppression, positional and positioning tests [the Dix–Hallpike and roll maneuvers for benign paroxysmal positional vertigo (BPPV)], C) Laboratory work out including CBC, fasting and postprandial blood sugar, kidney and liver function tests to rule out general systemic disorders. D) MRI of the brain was done in patients complaining of vertigo.
All subjects were subjected to the following procedures:
I. Audiological evaluation including: 1) Pure tone audiometry in the frequency range 250 – 8000 Hz at octave frequencies using Orbiter 922 audiometer in a sound treated room with a TDH 39 earphones. 2) Speech audiometry including speech reception threshold (SRT) using Arabic spondee words12, and word discrimination score (WDS), using, Arabic phonetically-balanced (PB) words13. 3) Tympanometry and acoustic reflex threshold testing using Grason-Stadler imittancemeter GSI 33 middle ear analyser version 2.
II. Vestibular Evoked Myogenic Potentials (VEMPs): VEMPs test was performed by using Schwarzer apparatus at the clinical neurophysiology unit at Kasr El-Aini Hospital. Subjects were seated upright comfortably in a quiet room. They were instructed to turn their heads to one side (away from the stimulated ear) to activate unilaterally the sterno-cleido-mastoid (SCM) muscle. They were instructed to push steadily their chin downwards against resistance. A two-channel recording montage of VEMP was used. Active electrodes were placed at the midpoint of the SCM muscle on each side of the neck, the reference electrodes were placed at the ipsilateral sterno-clavicular junctions, and the ground electrode was placed on the forehead. Rarefaction clicks were presented to each ear separately using head phones operating at intensity of 100 dB nHL. Two or three trials were obtained from each side to ensure reproducibility. The stimulus duration was 100-200 µsec. The gain was set to 2 µv/division. The sweep was set to 5 msec/division. The frequency of the stimulus was 5.1 stimulus/sec. The resulting response was averaged 125 times. The parameters evaluated were: the presence/absence of the response; latency of the first positive (P13) and negative (N23) peaks; peak to peak amplitude of P13-N23 complex; and right to left latency and amplitude difference.
III. Computerized Dynamic Posturography (CDP): All subjects reported normal or corrected vision by eye-glasses before the procedure. Sensory organization test (SOT) of the CDP: using the Equitest (Neurocom International, Clackamas, Oregon, USA) equipment. With the subject standing on a dual force plate, enclosed by a visual surround, estimating the position of the body sway. Subjects are exposed to six sensory conditions Nashner11: -SOT 1: Eyes open, steady surface and visual surround. -SOT 2: Eyes closed, steady surface and visual surround. -SOT 3: visual surround rotated, eyes open and platform steady. -SOT 4: Visual surround steady, platform rotated and eyes open. -SOT 5: Visual surround steady, platform rotated and eyes closed. -SOT 6: Platform and visual surround rotated with eyes open. Condition 5 and 6 scores best represent the vestibular part of the overall balance system21. A fall under any of the conditions = a score of 0% and a score of 100% when no sway at all. Equilibrium scores (ES): a total of 18 scores were obtained, 3 for each of the 6 conditions. The ES of each condition is the arithmetic mean of its 3 trials. Composite score (CS) is the mean overall score of the 18 test scores. When the composite score falls within the abnormal range, the second interpretation test "Sensory analyses (SA)" identifies the sensory dysfunction that contributed to the overall SOT abnormality: - Somatosensory ratio (SOM): measures ability to use somatosensory information. - Visual ratio (VIS): measures ability to use visual information. - Vestibular ratio (VEST): measures ability to use vestibular information. - Preference ratio (PREF): measures reliance of visual information.
IV) Rotatory vestibular test system: was done for 9 patients using CHARTR® RVT ICS. Frequencies used in SHA test included 0.01, 0.04. 0.16 & 0.64Hz.
Statistical Analysis of Data:
Calculations were done by means of statistical software package for social sciences (SPSS) version 11.5. Student’s t-test was used in testing significance for the comparison between means of two groups of quantitative (Numerical) data. One way ANOVA (Analysis of Variance) was used to compare between means of more than two groups. Chi-square X2) test was used for comparison between qualitative data which were presented as frequencies and percentages. Pearson’s correlation coefficient was used to determine significant correlations between the different quantitative variables. A difference was considered to be statistically significant (*) when the probability (p) value was £ 0.05.
RESULTS
Types of migraine and aura symptoms are shown in Table 1. The frequencies of symptoms including brainstem dysfunction are shown in Table 2. A total of 18 patients (75%) experienced symptoms of brainstem dysfunction.
Vertigo was considered when patient complained of sense of spinning while dizziness was considered when patient experiences lightheadedness without sense of rotation. Eleven (46%) of our patients experienced vertigo (10 females and 1 male) while only 2 (8%) patients who experienced dizziness. The temporal relation of vertigo/dizziness to headache and the duration of vertigo/dizziness are shown in Tables 3 & 4 respectively. Vertigo/dizziness were more common among migraineurs with aura than those without aura, however, the difference between the two groups was not statistically significant with a p-value 0.414. Three patients (27%) were found to have benign paroxysmal positional vertigo (BPPV) in the present study.
Regarding audiological tests, all migraineurs showed normal hearing threshold level, while only one patient showed severe sensorineural hearing loss at just the frequency of 8 KHz. All migraineurs showed type A tympanogram indicating normal middle ear function, with preserved acoustic reflexes.
On clinical examination, 3 patients showed vertical (upbeat) and tortional (towards the right) nystagmus by Dix-Hallpike test indicating right posterior canal BPPV. Otherwise, neuro-otological testing for studied patients revealed no abnormality.
As regards posturography, patients showed a statistically significant lower Condition 2 and Composite scores compared to the controls, and values fall below the 95% confidence interval (CI) for the mean of the controls. The SOM and VIS ratios were below the lower limit of 95% CI but their value was not statistically different from the controls (Table 5). Equilibrium Deficit was present in 37.5% (9) of our patients, of which deficits were observed in SOT condition 5 in 11.1%, in SOT condition 5 & 6 in 44.4% and in SOT condition 6 in 44.4%. There was no statistically significant difference between MA and MO as regards the equilibrium scores in any SOT condition or in the composite score. However, on performing sensory analyses, MO had statistically significant lower SOM ratio and PREF ratios than MA and SOM ratio in MO was below the lower limit of 95% CI (Table 6). There was no statistically significant difference between the migraineurs with and without vertigo/dizziness as regards equilibrium scores or the sensory analysis scores.
Equilibrium deficit and sensory analyses abnormality were detected in about 37.5% of those having aura, 25% of those having vertigo, 25% of those having symptoms of brainstem dysfunction and in none of those having dizziness. There was no statistically significant difference (p> 0.05) between the frequency of these symptoms in migraineurs with and without equilibrium abnormality.
On VEMP test, patients showed statistically significant delayed P13 and N23 latency values than the controls and values occur above the 95% confidence interval for the mean of the controls (Table 7). VEMPs abnormalities were present in 18 patients (75%), while 6 patients (25%) were without VEMP abnormality. In patients with abnormal VEMPs, 63.6% of patients were having vertigo/dizziness, whereas 36.4% were without vestibular symptoms. However, no statistically significant difference was detected between mean VEMP parameters in migraineurs with and without symptoms of vestibular dysfunction. VEMP abnormality was found in 66.7% of those having aura, 62.5% of those having vertigo, 100% of those having dizziness, 69.2% of those having symptoms of brainstem dysfunction. There was no statistically significant difference (p> 0.05) between the frequency of these symptoms in migraineurs with and without VEMP abnormality. There was no statistically significant difference (p> 0.05) between P13-N23 amplitude in migraineurs and controls.
Only 3 patients (12.5%) showed normal results in both VEMP and posturography. The majority of abnormal VEMP (87.5%) showed normal posturography results (equilibrium deficits, sensory analysis) and 50% of abnormal posturography showed normal VEMP (X2= 1.406; p= 0.378).There was a statistically significant inverse correlation (r= -0.491*; p= 0.033) between PREF ratio and age. There was no statistically significant correlation between VEMP parameters and age or duration of migraine or migraine attack duration. There was no statistically significant correlations between the VEMP parameters and the posturographic parameters except for a statistically significant inverse correlation between SOM ratio and the inter-side difference of P13 latency (r= -0.874**, p= 0.001) and inter-side difference of N23 (r= -0.662*, p= 0.037). As SOM ratio decreases, the inter-side difference latency increases.
A total of 9 cases had undergone rotatory chair test, of these, 3 patients (33.3%) showed abnormal gain and phase at higher frequencies than 0.04, indicating central nervous system dysfunction, one patient (11.1%) showed peripheral dysfunction (Lt Asymmetry) and 5 patients (55.6%) showed normal rotatory chair findings.