J Neurol DOI 10.1007/s00415-013-7221-7
ORIGINAL COMMUNICATION
Mastication-induced vertigo and nystagmus Seong-Ho Park • Hyo-Jung Kim • Ji-Soo Kim • Ja-Won Koo • Seo Won Oh • Dong-Uk Kim • Joon-Tae Kim Miriam Welgampola • Franca Deriu
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Received: 3 September 2013 / Revised: 13 December 2013 / Accepted: 13 December 2013 Ó Springer-Verlag Berlin Heidelberg 2013
Abstract Even though trigeminovestibular connections are well established in animals, mastication-induced dizziness has been described only as a vascular steal phenomenon in humans. We determined induction or modulation of nystagmus in two index patients with mastication-induced vertigo, 12 normal controls, and 52 additional patients with peripheral (n = 38, 26 with vestibular neuritis/labyrinthitis and 12 with Meniere’s disease) or central (n = 14, 11 with Wallenberg syndrome, two with cerebellar infarction, and one with pontine infarction) vestibulopathy during their acute or compensated phase. Both index patients developed mastication-induced vertigo after near complete resolution of the spontaneous vertigo from presumed acute unilateral peripheral vestibulopathy. The nystagmus and vertigo gradually built up during mastication and dissipated slowly after cessation of mastication. Brain MRI and cerebral angiography were normal in these patients. Mastication did not induce nystagmus in
normal controls. However, mastication induced nystagmus in five (24 %) of the 21 patients without spontaneous nystagmus (SN) but with a previous history of a vestibular syndrome, and either increased (21/31, 68 %) or decreased (7/31, 23 %) the SN in almost all the patients (28/31, 90 %) with SN. Mastication may induce significant vertigo and nystagmus in patients with a prior history of acute vestibulopathy. The induction or modulation of nystagmus by mastication in both peripheral and central vestibulopathies supports trigeminal modulation of the vestibular system in human. The gradual build-up and dissipation suggest a role of the velocity storage mechanism in the generation of mastication-induced vertigo and nystagmus. Keywords Nystagmus Vertigo Mastication Velocity storage Vestibular neuritis Cerebral infarction
Introduction Electronic supplementary material The online version of this article (doi:10.1007/s00415-013-7221-7) contains supplementary material, which is available to authorized users.
Various maneuvers may trigger vertigo and nystagmus according to the pathology involved [1]. Even though
S.-H. Park H.-J. Kim J.-S. Kim (&) S. W. Oh Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, Gyeonggi-do 463-707, Korea e-mail: [email protected]
J.-T. Kim Department of Neurology, Cerebrovascular Center, Chonnam National University Hospital, Gwangju, Korea
J.-W. Koo Department of Otolaryngology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
M. Welgampola Institute of Clinical Neurosciences, Central Clinical School, Royal Prince Alfred Hospital, University of Sidney, Sidney, Australia F. Deriu Department of Biomedical Sciences, University of Sassari, Sassari, Italy
D.-U. Kim Department of Neurology, Chosun University College of Medicine, Gwangju, Korea
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reciprocal connections exist between the trigeminal and vestibular systems [2], induction of dizziness or oscillopsia by mastication has been reported only as a mechanical [3] or vascular steal phenomenon [4]. Previously, a patient with a retro-orbital epidermoid cyst showed masticationinduced oscillopsia due to mechanical displacement of the tumor mass and the eye by a contracting temporalis muscle [3]. Another patient with an occlusion of the common carotid artery developed episodic dizziness, visual disturbance, and facial and extremity weakness in association with eating as a vascular steal syndrome [4]. This study was prompted by our anecdotal experiences with two patients who developed mastication-induced vertigo and nystagmus after recovery from a presumptive acute unilateral vestibulopathy. We characterized the nystagmus in those patients. Furthermore, to determine if this is a universal phenomenon, we explored modulation or induction of vertigo and nystagmus by mastication in normal controls and 53 patients with various causes of peripheral or central vestibulopathies.
Methods Subjects Between 2004 and 2011, we examined two patients with mastication-induced vertigo and nystagmus in the Dizziness Clinic of Seoul National University Bundang Hospital. To determine whether the mastication-induced modulation or induction of vertigo and nystagmus is a universal phenomenon, we additionally recruited 12 normal controls (10 women, age range 25–76, mean ± SD = 33.6 ± 13.2) and 52 patients with peripheral [n = 38, 26 with vestibular neuritis (VN)/labyrinthitis and 12 with Meniere’s disease] or central (n = 14, 11 with Wallenberg syndrome, two with cerebellar infarction, and one with pontine infarction) vestibulopathy during their acute or compensated phase. The diagnostic criteria of VN have been described previously [5]. Diagnosis of labyrinthitis was made when the patients had acute unilateral peripheral vestibulopathy and hearing loss without an MRI lesion that could otherwise explain these events [6]. Meniere’s disease was diagnosed when the patients met the definite diagnostic criteria of AAO-HNS [7]. All the patients with central vestibulopathy had a documented lesion on diffusionweighted MRI during their acute phase. All experiments followed the tenets of the Declaration of Helsinki and this study was approved by Institutional Review Board of Seoul National University Bundang Hospital.
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Oculography Spontaneous and triggered nystagmus were recorded using 3-dimensional video-oculography (SMI, Teltow, Germany) with a sampling rate of 60 Hz. The digitized eye position data were analyzed using MATLABÒ software (version R2011b; The MathWorks Inc., MA, USA) [8]. After recording the spontaneous nystagmus (SN) without fixation for 1 min, the subjects were asked to chew gum or beef jerky as they preferred. In the index patients, the mastication was maintained until the nystagmus was clearly evident and for as long as the patients could tolerate. The normal controls and additionally recruited patients were asked to maintain the mastication for 10 min. The recording continued for 5 min after cessation of the mastication. The mean slow-phase velocity (SPV) of SN was obtained by averaging the SPVs of ten consecutive nystagmus beats before mastication. To determine the presence of mastication-induced nystagmus, the mean SPV of SN was compared with the mean of the SPVs of ten consecutive nystagmus beats when the induced nystagmus was most intense. The temporal characteristics of the mastication-induced nystagmus were analyzed by plotting the SPVs over time. The decay time constant (TC) of mastication-induced nystagmus was calculated in the index patients using the basic equation, V = A*e-t/s ? C, where V is the SPV of the nystagmus, A is the amplitude, t is time, s is the TC, and C is the offset. Head-shaking-induced nystagmus (HSN) was assessed by using a passive head-shaking maneuver [8]. Vibrationinduced nystagmus (VIN) was recorded by applying a vibration stimulator to the forehead and both mastoids. The stimuli were given for 10 s at each location with an interval of 5 s [5]. Bedside horizontal head impulse tests (HITs) were performed manually with a rapid rotation of the head of approximately 20° amplitude in the horizontal plane. HIT was considered abnormal without recording when a corrective saccade was present [9]. Detailed methods of bithermal caloric tests, measurements of ocular torsion and tilt of subjective visual vertical (SVV), cervical vestibular-evoked myogenic potential (VEMP), and brain MRI have been described previously [5, 10]. Brain imaging MRI was performed in the two index patients and other patients with central vestibulopathy with an 1.5- or 3.0 T unit (Intera; Philips Medical Systems, Best, the Netherlands) using our standard imaging protocol (axial turbo spin-echo T2-weighted imaging, axial spin-echo
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T1-weighted imaging, and axial gradient-echo imaging). The imaging parameters were 4,800/100 [repetition time (ms)/echo time (ms)] for T2-weighted imaging, 500/11 for T1-weighted imaging, and 700/23 for gradient-echo imaging with a section thickness of 3 or 5 mm, a matrix size of 256 9 256 (interpolated to 512 9 512), and a fieldof-view of 200–220 mm. Diffusion-weighted imaging was additionally performed in the patients with acute infarction using the following parameters; b = 1,000, 4,119/89 (repetition time/echo time), section thickness of 3 or 5 mm, matrix of 128 9 128 (interpolated to 256 9 256), and field-of-view of 220 mm. Statistical analyses In the index patients, the modulation of SN by mastication was determined by comparing the SPVs of ten consecutive SN with those of nystagmus after modulation using the Student’s t test. Also, we compared the intensity of the nystagmus before and after mastication using paired t tests in the additionally recruited patients with peripheral or central vestibulopathy. Among the groups with different patterns of nystagmus modulation, the intervals from symptom onset to evaluation were compared with Kruskal– Wallis one-way ANOVA. The correlation of HSN and VIN with mastication-induced nystagmus was determined with a v2 test. The tests were performed using SPSS (version 15.0; SPSS, Chicago, IL) and values of p \ 0.05 were considered significant.
Results Index patients Case 1 A 61-year-old man presented with an 8-month history of vertigo that developed whenever he chewed his food. His first episode of vertigo, vomiting, and tinnitus occurred at dinner time, after which he had gone to bed earlier than usual. The next day, he awoke with severe spontaneous vertigo and vomiting that persisted for several days before subsiding. Thereafter, he began to experience vertigo and nausea induced by mastication. He denied any past medical histories or trauma, but reported fatigue due to physical exhaustion before the development of the vertigo. Both audiometry and caloric test were reported to be normal at that time. At the time of the referral, the patient had no spontaneous or gaze-evoked nystagmus and had normal bedside head impulse (HIT) and fistula tests. However, vibration stimuli on both mastoids and horizontal head-shaking induced subtle
right-beating nystagmus. He also showed right and upbeating nystagmus on lying down and head turning to either side while supine. Furthermore, chewing beef jerky for about 30 s began to induce vertigo and right-beating nystagmus. The horizontal right-beating component of induced nystagmus gradually built up with the SPV reaching around 20°/s during mastication for about 100 s, and slowly dissipated with a exponentially decreasing pattern (TC = 19.3 s) after cessation of mastication (Fig. 1, supplementary video 1). Saccades and smooth pursuit were normal. Audiometry, bithermal caloric tests, cervical VEMP, brain MRIs and MR angiography were all normal. Gabapentin 400 mg bid was started, but discontinued due to drowsiness. The mastication-induced vertigo gradually improved over the following year, and he reported mild dizziness only when he ate for a long time or when he felt tired. Case 2 A 36-year-old woman without a significant medical history was referred for evaluation of vertigo induced by mastication. She had suffered from vertigo and vomiting 3 months prior. The vertigo was spontaneous, without auditory and other neurological symptoms. The vertigo gradually improved over several days, but she began to experience vertigo, nausea, sweating, and general weakness with chewing 1 month later. The vertigo was relatively mild while eating soft foods, but most severe when eating solid ones such as cucumber. The masticationinduced vertigo initially lasted 10–20 min and gradually decreased to 3–5 min over a month. When the dizziness was severe, she also developed migrainous headaches. Brain MRIs were normal. When she was referred to our hospital 3 months later, she showed no spontaneous or gaze-evoked nystagmus. Horizontal head-shaking, vibratory stimuli on the brow, and positional testing did not induce vertigo or nystagmus. Bedside horizontal HIT and fistula test were normal. Other findings of general neurological examination were also normal. However, about 3 min after initiation of mastication, she began to develop vertigo and nystagmus. The nystagmus beat rightward, upward, and clockwise (from the patient’s point of view) and showed a marked suppression with fixation. The nystagmus gradually increased during and even after mastication for 7 min, reaching a plateau of the horizontal SPV at about 17°/s. Then the induced nystagmus decayed exponentially with a TC of 232.6 s (Fig. 2, supplementary video 2). While she showed mastication-induced nystagmus, bedside HIT was positive when the head was turned to the left. Bithermal caloric tests showed left caloric paresis of 28 %, but audiogram, subjective visual vertical, cervical VEMP, and brain MRI and MR angiography were normal. One month later, she
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Fig. 1 Recording of nystagmus induced by mastication in patient 1. a Mastication began to induce right-beating nystagmus about 30 s after initiation. The induced nystagmus gradually built up during mastication, and slowly dissipated after cessation of mastication. b Before mastication, no nystagmus was recorded. c During mastication, the patient shows nystagmus beating rightward and clockwise torsional (from the patient’s point of view). The pendular oscillations in the vertical plane were due to the head oscillations by chewing. d After discontinuation of mastication, the patient still shows
nystagmus beating rightward and clockwise torsional. e, f Plotting of the horizontal slow-phase velocity (SPV) shows a gradual build-up of the induced nystagmus during mastication for about 100 s, and an exponential decay of the nystagmus with a time constant of 19.3 s after discontinuation of the mastication. Please note vertical pendular oscillation of the eyes during mastication in a and c. Upward deflection in each trace indicates rightward, upward, and clockwise eye motion
reported a marked improvement of the symptoms: mild dizziness while eating noodles and more severe dizziness when chewing meat. The dizziness gradually resolved over the several months.
Overall, mastication induced nystagmus in five (24 %, two with VN and three with Meniere’s disease) of the 21 patients without SN, and modulated the SN in almost all the patients (28/31, 90 %) with SN [increase in 21 (21/31, 68 %), and decrease in seven (7/31, 23 %)] (Table 1). Of the 26 patients with VN or labyrinthitis, 18 (18/26, 69 %) had SN, and 11 (11/18, 61 %) of them showed increase while five (5/18, 28 %) exhibited decrease of the SN. Furthermore, mastication induced nystagmus in two (25 %) of the eight patients without SN. However, two patients with recovery nystagmus, the nystagmus in the opposite direction of initial nystagmus due to central compensation during recovery, did not show any modulation of the nystagmus by mastication (Table 1). Overall, there were no differences in the interval from the symptom to evaluation among the three groups with different patterns of modulation (increase vs. decrease vs. no change, Kruskal–Wallis one-way ANOVA, p = 0.247).
Mastication-induced nystagmus in normal controls and additional patients with vestibular disorders Mastication did not induce nystagmus in normal controls. However, mastication induced nystagmus or significantly modulated pre-existing horizontal SN in patients with vestibulopathy (paired t test, p = 0.001), both in peripheral (paired t test, p = 0.008) and central (paired t test, p = 0.028) vestibular disorders (Fig. 3), even though none of the additional patients reported a significant change or induction of dizziness with mastication. None of them reported additional auditory symptoms, either.
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J Neurol Fig. 2 Recording of nystagmus induced by mastication in patient 2. a Mastication began to induce nystagmus about 3 min after initiation and gradually increased during mastication for 7 min. The nystagmus beat rightward, upward, and clockwise. After cessation of mastication, the nystagmus lasted about 30 min. The recording was paused twice for bedside HIT. b Before mastication, no nystagmus was present. c During mastication, the patient shows nystagmus beating rightward, upward, and clockwise torsional. d After discontinuation of mastication, the patient shows more vigorous nystagmus. e The nystagmus is markedly suppressed by visual fixation. f Plotting of the horizontal slow-phase velocity (SPV) shows a gradual build-up of the induced nystagmus during and even after mastication, reaching a plateau at about 17°/s. g Then, the induced nystagmus decayed exponentially with a time constant of 232.6 s
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J Neurol Table 1 Patterns of spontaneous and mastication-induced nystagmus in our patients Vestibulopathy
Spontaneous nystagmus
Vestibular neuritis/ labyrinthitis (n = 26)
Yes (n = 18)
Mastication-induced nystagmus Increase (n = 11) Decrease (n = 5)
No (n = 8)
No change (n = 2)a Induction (n = 2) No induction (n = 6)
Meniere’s (n = 12)
Yes (n = 4)b
Increase (n = 3) Decrease (n = 0) No change (n = 1)
No (n = 8)
Induction (n = 3)c No induction (n = 5)
Central (n = 14)
Yes (n = 9)
Increase (n = 7) Decrease (n = 2) No change (n = 0)
No (n = 5)
Induction (n = 0) No induction (n = 5)
Fig. 3 Induction and modulation of nystagmus in the additional patients with peripheral and central vestibular disorders. Mastication induced nystagmus or significantly modulated pre-existing horizontal spontaneous nystagmus (SN) in patients with vestibular disorders (paired t test, p = 0.001), both in peripheral (paired t test, p = 0.008) and central (paired t test, p = 0.028) types. Mastication induced nystagmus in five (24 %) of the 21 patients without SN, and either increased (21/31, 68 %) or decreased (7/31, 23 %) the SN in almost all the patients (28/31, 90 %) with SN. The figures in the graph indicate the number of patients overlapped on each corresponding point. VN vestibular neuritis
Total (n = 52)
Yes (n = 31)
Increase (n = 21) Decrease (n = 7)
No (n = 21)
No change (n = 3) Induction (n = 5) No induction (n = 16)
a
These two patients had recovery nystagmus at the time of evaluation
b
All four patients had a paretic pattern of nystagmus when they underwent evaluation
c
Of the 12 patients with Meniere’s disease, four with SN during the paretic phase underwent evaluation, and three of them had an increase of the nystagmus while the remaining one showed no modulation of the nystagmus by mastication. Furthermore, mastication induced nystagmus in three (37 %) of the eight patients without SN, two with an irritative pattern and one with a paretic pattern (Table 1). Of the 14 patients with central vestibular disorders, nine (64 %) with SN showed either increase (n = 7, 78 %) or decrease (n = 2, 22 %) of the SN by mastication. However, mastication did not induce nystagmus in all of the five without SN (Table 1). Again, there were no differences in the interval from the symptom to evaluation among the three groups with different patterns of modulation (increase vs. decrease vs. no change, Kruskal–Wallis one-way ANOVA, p = 0.820). The patients showed three distinctive patterns of induction or modulation of nystagmus by mastication. In most patients (27/33, 81.8 %), mastication gradually built up the nystagmus over 70 s to 11.5 min (mean ± SD 224 ± 194 s). Then, the induced nystagmus gradually dissipated after variable durations of plateau (Fig. 4a). In five patients (5/33, 15.2 %), mastication gradually
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The patterns of the induced nystagmus were either irritative (n = 2) or paretic (n = 1)
suppressed the spontaneous nystagmus with an exponentially decreasing pattern, and this suppressive effect lasted even after cessation of the mastication until the termination of observation (Fig. 4b). Only a patient with acute VN showed a mild suppression of the SN during the mastication and a rather abrupt increase of the nystagmus just after cessation of the mastication, which was also followed by a gradual decrease (Fig. 4c). Correlation of mastication-induced nystagmus with head-shaking and vibration-induced nystagmus Head-shaking showed an induction or modulations of nystagmus in 24 (49.0 %) of the 49 patients tested; 58.3 % (14/24) in the VN/labyrinthitis group, 50 % (6/12) in the Meniere’s group, and 30.8 % (4/13) in the central group. HSN did not correlate with induction or modulation of the nystagmus by mastication (v2 test, p = 0.095). Vibration induced or modulated nystagmus in 19 (39.6 %) of the 48 patients tested; 56.5 % (13/23) in the VN/labyrinthitis group, 33.3 % (4/12) in the Meniere’s
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normal, excluding a significant asymmetry, while normal brain MRIs and MR angiography excluded a structural lesion or vascular steal phenomenon as a possible explanation for mastication-induced vertigo and nystagmus. We hypothesize that the development of vertigo and nystagmus during mastication indicates an unmasking of latent vestibular asymmetry by trigeminal stimulation (activation). Reciprocal connections between the vestibular and trigeminal systems
Fig. 4 Patterns of nystagmus modulation by mastication in the additional patients. a Most patients (27/33, 81.8 %) showed a gradual build-up of the nystagmus by mastication and gradual dissipation of the induced nystagmus after variable durations of plateau. b Five patients (5/33, 15.2 %) had a gradual suppression of the spontaneous nystagmus by mastication, which lasted even after cessation of the mastication. c Only a patient with acute VN showed a mild suppression of the spontaneous nystagmus during the mastication and a rather abrupt increase just after cessation of the mastication, which is also followed by a gradual decrease. The arrow in each figure indicates the duration of mastication
group, and 15.4 % (2/13) in the central group. The development of VIN did not correlate with induction of mastication-induced nystagmus, either (v2 test, p = 0.195).
Discussion Both index patients developed mastication-induced vertigo and nystagmus several months after near complete resolution of an episode consistent with acute unilateral vestibulopathy. In both subjects, the vertigo and nystagmus built up gradually during the mastication and dissipated slowly after cessation of the mastication. Interictal neurotological evaluations were
There are experimental evidences of reciprocal projections between the trigeminal sensory nucleus and vestibular nuclei/nucleus prepositus hypoglossi in rats [2, 11–14]. Neurons in the caudal part of the trigeminal mesencephalic nucleus project mainly to the medial, inferior, and lateral vestibular nuclei, and moderately to the peripheral part of the superior vestibular nuclei [12]. Also, trigeminal mesencephalic neurons project directly to the cerebellum, which is involved in the control and coordination of eye– head movements [15]. Individual neurons of the mesencephalic nucleus send collaterals to the vestibular nuclei and the vestibulo-cerebellum [12]. The direct primary projection from the mesencephalic nucleus to the MVN is known to convey proprioceptive information from the face and extraocular muscles [2, 16]. In another study, the trigeminovestibular projection was predominantly of mandibular origin [11]. There are direct mandibular [17] and secondary trigeminal afferents to the vestibular nuclei [18, 19]. Vestibular nuclei and nucleus prepositus hypoglossi also project to the trigeminal nucleus [20, 21]. The MVN appears to be the integration center for the trigeminal-vestibular interaction since most of the vestibular projections to the motor trigeminal nucleus originate from the MVN and nucleus prepositus hypoglossi [13, 14]. Trigeminal modulation of the vestibular activity in animals In guinea pigs, electrical stimulation of the trigeminal nerve and nociceptive cutaneous stimulation of the face modulate spontaneous activity of the vestibular neuron with a latency of 1.2–6.2 ms [22]. Also, inputs from the perioral whiskers (i.e., direction of their bending) may be used in determining heading in lower vertebrates and in non-human primates [23]. Accordingly, trigeminal stimulations may change the discharge rate or evoke rhythmic activity in the vestibular neuron [22]. However, the effects induced by trigeminal stimulation were usually shorter and weaker than those by labyrinthine stimulation. Accordingly, even though trigeminal stimulation per se cannot induce eye movements, it may modulate preexisting nystagmus [22]. Modulation of the vestibular nystagmus by trigeminal stimulation has long been recognized
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[24]. The trigeminal modulation of vestibular activity suggests a trigeminal role in the control of posture and orientation [22], and a vestibular role in the actuation and coordination of trigeminal reflexes [25–27]. The vestibular system by the way of its spinal and trigeminal projections may modulate the transmission of information from the neck as well as from the face [2, 28, 29]. In guinea pigs compensated from unilateral labyrinthectomy, unilateral trigeminal neurotomy increases the amplitude of vestibular field potentials recorded from intact vestibular nuclei [30]. Trigeminal neurotomy also induces vestibular decompensation in guinea pigs that were compensated from hemilabyrinthectomy, which results in reemergence of nystagmus, head torsion, curvature of the trunk, extension of the forelimb, circling and rolling movements, and impaired righting reflexes [31]. These signs of decompensation lasted for 6–8 h after trigeminal neurotomy. Trigeminal stimulation as well as unilateral trigeminal neurotomy may disclose latent vestibular nystagmus after hemilabyrinthectomy [31, 32]. In view of these findings, the trigeminal system appears to contribute to vestibular compensation by inhibiting the hyperactive vestibular nuclei on the intact side and by decreasing tonic commissural inhibitory influences on the deafferentiated vestibular nuclei [22]. Furthermore, microstimulation of the motor trigeminal nucleus induces nystagmus in anaesthetized rats (Dr. Deriu: unpublished observations).
Induction or modulation of nystagmus by mastication in vestibular disorders Our study indicates that trigeminal modulation of the vestibular system is a universal phenomenon in humans by demonstrating modulation of the nystagmus by mastication in patients with vestibulopathy of variable causes. While mastication did not induce nystagmus in normal controls, almost all the patients with SN showed modulation of SN by mastication. Furthermore, mastication induced nystagmus in five of 21 patients without SN. However, the patterns of modulation varied, and the mechanisms of these various modulations remain unknown. The modulation patterns may be related to the interval from symptom onset to evaluation. However, there were no differences in the interval among the groups with different patterns of modulation in both VN/labyrinthitis and central vestibular disorders. Of interest, three of the four patients with Meniere’s disease showed an augmentation of the SN with mastication during the paretic phase. However, the induced nystagmus in the Meniere’s patients without SN was either paretic or irritative. Otherwise, the modulation may have been affected by the side of predominant chewing, which could not be monitored in our study. Individual variations in the trigeminovestibular connection remain another possibility.
Trigeminal modulation of vestibular activity in humans
Characteristics and mechanism of mastication-induced vertigo and nystagmus
The modulation of vestibular nystagmus by trigeminal stimulation has long been known since the work by Lorente de No in rabbits [24]. In humans, however, there has been a paucity of data on trigeminovestibular modulation, even though several studies have documented the vestibular modulation of the trigeminal activities [33, 34]. In patients with migraine, painful trigeminal stimulation elicits nystagmus or generally increases pre-existing spontaneous nystagmus [35]. The evoked nystagmus has a mean latency of 25 s and a rather variable duration [35]. The nystagmus shows a linear slow phase and visual suppression, which suggests a vestibular nystagmus of peripheral origin [35]. These findings also indicate that trigeminal activation may induce an imbalance of the vestibular system in humans. One of our index patients developed migraines when she developed severe mastication-induced vertigo. She also showed a marked suppression of mastication-induced nystagmus by visual fixation and abnormal HIT only after developing mastication-induced nystagmus. These findings also suggest nystagmus of vestibular origin. These patients with migraines may be more susceptible to trigeminal modulation of the vestibular system.
Of interest, our index patients developed masticationinduced vertigo and nystagmus several months after an episode consistent with acute unilateral vestibulopathy. The near complete resolution of symptoms during the intervening periods indicates a compensation for the preceding unilateral vestibulopathy. It remains unclear why the mastication-induced vestibular imbalance developed several months after the remission of the acute symptoms. Otherwise, it may have been masked by acute symptoms. In our index patients, the nystagmus began to build up with a latency of several minutes after initiation of mastication, and gradually dissipated after discontinuation of mastication. These features are also characteristic of nystagmus induced by head-shaking, which is explained by asymmetrical vestibular input and central velocity storage mechanism [36]. The velocity storage mechanism contributes to an accumulation of the vestibular inputs during repetitive stimulation, which is known to be attained by the vestibular nuclei and the commissural fibers connecting them [37]. During mastication, the gradual accumulation of vestibular asymmetry due to decompensation may have been discharged as nystagmus in our patients.
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Unilateral vestibular hypofunction or asymmetric central vestibulopathy often leads to central vestibular asymmetry. In peripheral vestibulopathies, transient nystagmus often occurs after skull bone vibration or after head shaking due to unequal stimulation of the vestibular system between two sides. The nystagmus lateralizes to the abnormal side with hypofunction. The same principle may be applied during mastication. As we chew, more so in the case of crunchy and brittle food such as cucumber, high-frequency vibrations may be transmitted to the labyrinth via the jaw bones. These vibrations, when repeated over time due to constant chewing, can lead to asymmetric stimulation of the vestibular end organ and result in asymmetric build-up of tone in the vestibular nuclei in peripheral vestibulopathies, or asymmetric build-up of tone in the vestibular nuclei in central vestibulopathies. Such asymmetry then causes mastication-induced nystagmus. The rate at which nystagmus emerges would depend upon how rapidly the asymmetry develops between two sides, and dissipation of nystagmus after cessation of mastication would depend upon the decay TC of the vestibular velocity storage. However, our patients did not show any correlation between the VIN/HSN and the mastication-induced nystagmus. Otherwise, the latency may be related to the time required for the vasodilator effect to appear in rat facial skin after electrical stimulation of the trigeminal ganglion, an effect mediated by the release of calcitonin gene-related peptide (CGRP) [38]. Alternatively, trigeminal stimulus activates the efferent olivocochlear system through the connections between the trigeminal sensory and vestibular nuclei in the brainstem [11]. Acknowledgments The authors are grateful to Professor Thomas Brandt for his helpful comments in preparing this manuscript. This study was supported by a grant from the Korea Medical Devices Industrial Cooperative Association and the Small and Medium Business Administration (08-2011-065). Conflicts of interest Dr. Kim serves as an Associate Editor of Frontiers in Neuro-otology and on the editorial boards of the Journal of Korean Society of Clinical Neurophysiology, Research in Vestibular Science, Journal of Clinical Neurology, Frontiers in Neuroophthalmology, Journal of Neuro-ophthalmology, and Case Reports in Ophthalmological Medicine; he has received research support from SK Chemicals, Co. Ltd. SH Park, JW Koo, DU Kim, JT Kim, HJ Kim, Oh, Welgampola, and Deriu report no conflicts of interest.
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ORIGINAL COMMUNICATION
Mastication-induced vertigo and nystagmus Seong-Ho Park • Hyo-Jung Kim • Ji-Soo Kim • Ja-Won Koo • Seo Won Oh • Dong-Uk Kim • Joon-Tae Kim Miriam Welgampola • Franca Deriu
•
Received: 3 September 2013 / Revised: 13 December 2013 / Accepted: 13 December 2013 Ó Springer-Verlag Berlin Heidelberg 2013
Abstract Even though trigeminovestibular connections are well established in animals, mastication-induced dizziness has been described only as a vascular steal phenomenon in humans. We determined induction or modulation of nystagmus in two index patients with mastication-induced vertigo, 12 normal controls, and 52 additional patients with peripheral (n = 38, 26 with vestibular neuritis/labyrinthitis and 12 with Meniere’s disease) or central (n = 14, 11 with Wallenberg syndrome, two with cerebellar infarction, and one with pontine infarction) vestibulopathy during their acute or compensated phase. Both index patients developed mastication-induced vertigo after near complete resolution of the spontaneous vertigo from presumed acute unilateral peripheral vestibulopathy. The nystagmus and vertigo gradually built up during mastication and dissipated slowly after cessation of mastication. Brain MRI and cerebral angiography were normal in these patients. Mastication did not induce nystagmus in
normal controls. However, mastication induced nystagmus in five (24 %) of the 21 patients without spontaneous nystagmus (SN) but with a previous history of a vestibular syndrome, and either increased (21/31, 68 %) or decreased (7/31, 23 %) the SN in almost all the patients (28/31, 90 %) with SN. Mastication may induce significant vertigo and nystagmus in patients with a prior history of acute vestibulopathy. The induction or modulation of nystagmus by mastication in both peripheral and central vestibulopathies supports trigeminal modulation of the vestibular system in human. The gradual build-up and dissipation suggest a role of the velocity storage mechanism in the generation of mastication-induced vertigo and nystagmus. Keywords Nystagmus Vertigo Mastication Velocity storage Vestibular neuritis Cerebral infarction
Introduction Electronic supplementary material The online version of this article (doi:10.1007/s00415-013-7221-7) contains supplementary material, which is available to authorized users.
Various maneuvers may trigger vertigo and nystagmus according to the pathology involved [1]. Even though
S.-H. Park H.-J. Kim J.-S. Kim (&) S. W. Oh Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, Gyeonggi-do 463-707, Korea e-mail: [email protected]
J.-T. Kim Department of Neurology, Cerebrovascular Center, Chonnam National University Hospital, Gwangju, Korea
J.-W. Koo Department of Otolaryngology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
M. Welgampola Institute of Clinical Neurosciences, Central Clinical School, Royal Prince Alfred Hospital, University of Sidney, Sidney, Australia F. Deriu Department of Biomedical Sciences, University of Sassari, Sassari, Italy
D.-U. Kim Department of Neurology, Chosun University College of Medicine, Gwangju, Korea
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reciprocal connections exist between the trigeminal and vestibular systems [2], induction of dizziness or oscillopsia by mastication has been reported only as a mechanical [3] or vascular steal phenomenon [4]. Previously, a patient with a retro-orbital epidermoid cyst showed masticationinduced oscillopsia due to mechanical displacement of the tumor mass and the eye by a contracting temporalis muscle [3]. Another patient with an occlusion of the common carotid artery developed episodic dizziness, visual disturbance, and facial and extremity weakness in association with eating as a vascular steal syndrome [4]. This study was prompted by our anecdotal experiences with two patients who developed mastication-induced vertigo and nystagmus after recovery from a presumptive acute unilateral vestibulopathy. We characterized the nystagmus in those patients. Furthermore, to determine if this is a universal phenomenon, we explored modulation or induction of vertigo and nystagmus by mastication in normal controls and 53 patients with various causes of peripheral or central vestibulopathies.
Methods Subjects Between 2004 and 2011, we examined two patients with mastication-induced vertigo and nystagmus in the Dizziness Clinic of Seoul National University Bundang Hospital. To determine whether the mastication-induced modulation or induction of vertigo and nystagmus is a universal phenomenon, we additionally recruited 12 normal controls (10 women, age range 25–76, mean ± SD = 33.6 ± 13.2) and 52 patients with peripheral [n = 38, 26 with vestibular neuritis (VN)/labyrinthitis and 12 with Meniere’s disease] or central (n = 14, 11 with Wallenberg syndrome, two with cerebellar infarction, and one with pontine infarction) vestibulopathy during their acute or compensated phase. The diagnostic criteria of VN have been described previously [5]. Diagnosis of labyrinthitis was made when the patients had acute unilateral peripheral vestibulopathy and hearing loss without an MRI lesion that could otherwise explain these events [6]. Meniere’s disease was diagnosed when the patients met the definite diagnostic criteria of AAO-HNS [7]. All the patients with central vestibulopathy had a documented lesion on diffusionweighted MRI during their acute phase. All experiments followed the tenets of the Declaration of Helsinki and this study was approved by Institutional Review Board of Seoul National University Bundang Hospital.
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Oculography Spontaneous and triggered nystagmus were recorded using 3-dimensional video-oculography (SMI, Teltow, Germany) with a sampling rate of 60 Hz. The digitized eye position data were analyzed using MATLABÒ software (version R2011b; The MathWorks Inc., MA, USA) [8]. After recording the spontaneous nystagmus (SN) without fixation for 1 min, the subjects were asked to chew gum or beef jerky as they preferred. In the index patients, the mastication was maintained until the nystagmus was clearly evident and for as long as the patients could tolerate. The normal controls and additionally recruited patients were asked to maintain the mastication for 10 min. The recording continued for 5 min after cessation of the mastication. The mean slow-phase velocity (SPV) of SN was obtained by averaging the SPVs of ten consecutive nystagmus beats before mastication. To determine the presence of mastication-induced nystagmus, the mean SPV of SN was compared with the mean of the SPVs of ten consecutive nystagmus beats when the induced nystagmus was most intense. The temporal characteristics of the mastication-induced nystagmus were analyzed by plotting the SPVs over time. The decay time constant (TC) of mastication-induced nystagmus was calculated in the index patients using the basic equation, V = A*e-t/s ? C, where V is the SPV of the nystagmus, A is the amplitude, t is time, s is the TC, and C is the offset. Head-shaking-induced nystagmus (HSN) was assessed by using a passive head-shaking maneuver [8]. Vibrationinduced nystagmus (VIN) was recorded by applying a vibration stimulator to the forehead and both mastoids. The stimuli were given for 10 s at each location with an interval of 5 s [5]. Bedside horizontal head impulse tests (HITs) were performed manually with a rapid rotation of the head of approximately 20° amplitude in the horizontal plane. HIT was considered abnormal without recording when a corrective saccade was present [9]. Detailed methods of bithermal caloric tests, measurements of ocular torsion and tilt of subjective visual vertical (SVV), cervical vestibular-evoked myogenic potential (VEMP), and brain MRI have been described previously [5, 10]. Brain imaging MRI was performed in the two index patients and other patients with central vestibulopathy with an 1.5- or 3.0 T unit (Intera; Philips Medical Systems, Best, the Netherlands) using our standard imaging protocol (axial turbo spin-echo T2-weighted imaging, axial spin-echo
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T1-weighted imaging, and axial gradient-echo imaging). The imaging parameters were 4,800/100 [repetition time (ms)/echo time (ms)] for T2-weighted imaging, 500/11 for T1-weighted imaging, and 700/23 for gradient-echo imaging with a section thickness of 3 or 5 mm, a matrix size of 256 9 256 (interpolated to 512 9 512), and a fieldof-view of 200–220 mm. Diffusion-weighted imaging was additionally performed in the patients with acute infarction using the following parameters; b = 1,000, 4,119/89 (repetition time/echo time), section thickness of 3 or 5 mm, matrix of 128 9 128 (interpolated to 256 9 256), and field-of-view of 220 mm. Statistical analyses In the index patients, the modulation of SN by mastication was determined by comparing the SPVs of ten consecutive SN with those of nystagmus after modulation using the Student’s t test. Also, we compared the intensity of the nystagmus before and after mastication using paired t tests in the additionally recruited patients with peripheral or central vestibulopathy. Among the groups with different patterns of nystagmus modulation, the intervals from symptom onset to evaluation were compared with Kruskal– Wallis one-way ANOVA. The correlation of HSN and VIN with mastication-induced nystagmus was determined with a v2 test. The tests were performed using SPSS (version 15.0; SPSS, Chicago, IL) and values of p \ 0.05 were considered significant.
Results Index patients Case 1 A 61-year-old man presented with an 8-month history of vertigo that developed whenever he chewed his food. His first episode of vertigo, vomiting, and tinnitus occurred at dinner time, after which he had gone to bed earlier than usual. The next day, he awoke with severe spontaneous vertigo and vomiting that persisted for several days before subsiding. Thereafter, he began to experience vertigo and nausea induced by mastication. He denied any past medical histories or trauma, but reported fatigue due to physical exhaustion before the development of the vertigo. Both audiometry and caloric test were reported to be normal at that time. At the time of the referral, the patient had no spontaneous or gaze-evoked nystagmus and had normal bedside head impulse (HIT) and fistula tests. However, vibration stimuli on both mastoids and horizontal head-shaking induced subtle
right-beating nystagmus. He also showed right and upbeating nystagmus on lying down and head turning to either side while supine. Furthermore, chewing beef jerky for about 30 s began to induce vertigo and right-beating nystagmus. The horizontal right-beating component of induced nystagmus gradually built up with the SPV reaching around 20°/s during mastication for about 100 s, and slowly dissipated with a exponentially decreasing pattern (TC = 19.3 s) after cessation of mastication (Fig. 1, supplementary video 1). Saccades and smooth pursuit were normal. Audiometry, bithermal caloric tests, cervical VEMP, brain MRIs and MR angiography were all normal. Gabapentin 400 mg bid was started, but discontinued due to drowsiness. The mastication-induced vertigo gradually improved over the following year, and he reported mild dizziness only when he ate for a long time or when he felt tired. Case 2 A 36-year-old woman without a significant medical history was referred for evaluation of vertigo induced by mastication. She had suffered from vertigo and vomiting 3 months prior. The vertigo was spontaneous, without auditory and other neurological symptoms. The vertigo gradually improved over several days, but she began to experience vertigo, nausea, sweating, and general weakness with chewing 1 month later. The vertigo was relatively mild while eating soft foods, but most severe when eating solid ones such as cucumber. The masticationinduced vertigo initially lasted 10–20 min and gradually decreased to 3–5 min over a month. When the dizziness was severe, she also developed migrainous headaches. Brain MRIs were normal. When she was referred to our hospital 3 months later, she showed no spontaneous or gaze-evoked nystagmus. Horizontal head-shaking, vibratory stimuli on the brow, and positional testing did not induce vertigo or nystagmus. Bedside horizontal HIT and fistula test were normal. Other findings of general neurological examination were also normal. However, about 3 min after initiation of mastication, she began to develop vertigo and nystagmus. The nystagmus beat rightward, upward, and clockwise (from the patient’s point of view) and showed a marked suppression with fixation. The nystagmus gradually increased during and even after mastication for 7 min, reaching a plateau of the horizontal SPV at about 17°/s. Then the induced nystagmus decayed exponentially with a TC of 232.6 s (Fig. 2, supplementary video 2). While she showed mastication-induced nystagmus, bedside HIT was positive when the head was turned to the left. Bithermal caloric tests showed left caloric paresis of 28 %, but audiogram, subjective visual vertical, cervical VEMP, and brain MRI and MR angiography were normal. One month later, she
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Fig. 1 Recording of nystagmus induced by mastication in patient 1. a Mastication began to induce right-beating nystagmus about 30 s after initiation. The induced nystagmus gradually built up during mastication, and slowly dissipated after cessation of mastication. b Before mastication, no nystagmus was recorded. c During mastication, the patient shows nystagmus beating rightward and clockwise torsional (from the patient’s point of view). The pendular oscillations in the vertical plane were due to the head oscillations by chewing. d After discontinuation of mastication, the patient still shows
nystagmus beating rightward and clockwise torsional. e, f Plotting of the horizontal slow-phase velocity (SPV) shows a gradual build-up of the induced nystagmus during mastication for about 100 s, and an exponential decay of the nystagmus with a time constant of 19.3 s after discontinuation of the mastication. Please note vertical pendular oscillation of the eyes during mastication in a and c. Upward deflection in each trace indicates rightward, upward, and clockwise eye motion
reported a marked improvement of the symptoms: mild dizziness while eating noodles and more severe dizziness when chewing meat. The dizziness gradually resolved over the several months.
Overall, mastication induced nystagmus in five (24 %, two with VN and three with Meniere’s disease) of the 21 patients without SN, and modulated the SN in almost all the patients (28/31, 90 %) with SN [increase in 21 (21/31, 68 %), and decrease in seven (7/31, 23 %)] (Table 1). Of the 26 patients with VN or labyrinthitis, 18 (18/26, 69 %) had SN, and 11 (11/18, 61 %) of them showed increase while five (5/18, 28 %) exhibited decrease of the SN. Furthermore, mastication induced nystagmus in two (25 %) of the eight patients without SN. However, two patients with recovery nystagmus, the nystagmus in the opposite direction of initial nystagmus due to central compensation during recovery, did not show any modulation of the nystagmus by mastication (Table 1). Overall, there were no differences in the interval from the symptom to evaluation among the three groups with different patterns of modulation (increase vs. decrease vs. no change, Kruskal–Wallis one-way ANOVA, p = 0.247).
Mastication-induced nystagmus in normal controls and additional patients with vestibular disorders Mastication did not induce nystagmus in normal controls. However, mastication induced nystagmus or significantly modulated pre-existing horizontal SN in patients with vestibulopathy (paired t test, p = 0.001), both in peripheral (paired t test, p = 0.008) and central (paired t test, p = 0.028) vestibular disorders (Fig. 3), even though none of the additional patients reported a significant change or induction of dizziness with mastication. None of them reported additional auditory symptoms, either.
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J Neurol Fig. 2 Recording of nystagmus induced by mastication in patient 2. a Mastication began to induce nystagmus about 3 min after initiation and gradually increased during mastication for 7 min. The nystagmus beat rightward, upward, and clockwise. After cessation of mastication, the nystagmus lasted about 30 min. The recording was paused twice for bedside HIT. b Before mastication, no nystagmus was present. c During mastication, the patient shows nystagmus beating rightward, upward, and clockwise torsional. d After discontinuation of mastication, the patient shows more vigorous nystagmus. e The nystagmus is markedly suppressed by visual fixation. f Plotting of the horizontal slow-phase velocity (SPV) shows a gradual build-up of the induced nystagmus during and even after mastication, reaching a plateau at about 17°/s. g Then, the induced nystagmus decayed exponentially with a time constant of 232.6 s
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J Neurol Table 1 Patterns of spontaneous and mastication-induced nystagmus in our patients Vestibulopathy
Spontaneous nystagmus
Vestibular neuritis/ labyrinthitis (n = 26)
Yes (n = 18)
Mastication-induced nystagmus Increase (n = 11) Decrease (n = 5)
No (n = 8)
No change (n = 2)a Induction (n = 2) No induction (n = 6)
Meniere’s (n = 12)
Yes (n = 4)b
Increase (n = 3) Decrease (n = 0) No change (n = 1)
No (n = 8)
Induction (n = 3)c No induction (n = 5)
Central (n = 14)
Yes (n = 9)
Increase (n = 7) Decrease (n = 2) No change (n = 0)
No (n = 5)
Induction (n = 0) No induction (n = 5)
Fig. 3 Induction and modulation of nystagmus in the additional patients with peripheral and central vestibular disorders. Mastication induced nystagmus or significantly modulated pre-existing horizontal spontaneous nystagmus (SN) in patients with vestibular disorders (paired t test, p = 0.001), both in peripheral (paired t test, p = 0.008) and central (paired t test, p = 0.028) types. Mastication induced nystagmus in five (24 %) of the 21 patients without SN, and either increased (21/31, 68 %) or decreased (7/31, 23 %) the SN in almost all the patients (28/31, 90 %) with SN. The figures in the graph indicate the number of patients overlapped on each corresponding point. VN vestibular neuritis
Total (n = 52)
Yes (n = 31)
Increase (n = 21) Decrease (n = 7)
No (n = 21)
No change (n = 3) Induction (n = 5) No induction (n = 16)
a
These two patients had recovery nystagmus at the time of evaluation
b
All four patients had a paretic pattern of nystagmus when they underwent evaluation
c
Of the 12 patients with Meniere’s disease, four with SN during the paretic phase underwent evaluation, and three of them had an increase of the nystagmus while the remaining one showed no modulation of the nystagmus by mastication. Furthermore, mastication induced nystagmus in three (37 %) of the eight patients without SN, two with an irritative pattern and one with a paretic pattern (Table 1). Of the 14 patients with central vestibular disorders, nine (64 %) with SN showed either increase (n = 7, 78 %) or decrease (n = 2, 22 %) of the SN by mastication. However, mastication did not induce nystagmus in all of the five without SN (Table 1). Again, there were no differences in the interval from the symptom to evaluation among the three groups with different patterns of modulation (increase vs. decrease vs. no change, Kruskal–Wallis one-way ANOVA, p = 0.820). The patients showed three distinctive patterns of induction or modulation of nystagmus by mastication. In most patients (27/33, 81.8 %), mastication gradually built up the nystagmus over 70 s to 11.5 min (mean ± SD 224 ± 194 s). Then, the induced nystagmus gradually dissipated after variable durations of plateau (Fig. 4a). In five patients (5/33, 15.2 %), mastication gradually
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The patterns of the induced nystagmus were either irritative (n = 2) or paretic (n = 1)
suppressed the spontaneous nystagmus with an exponentially decreasing pattern, and this suppressive effect lasted even after cessation of the mastication until the termination of observation (Fig. 4b). Only a patient with acute VN showed a mild suppression of the SN during the mastication and a rather abrupt increase of the nystagmus just after cessation of the mastication, which was also followed by a gradual decrease (Fig. 4c). Correlation of mastication-induced nystagmus with head-shaking and vibration-induced nystagmus Head-shaking showed an induction or modulations of nystagmus in 24 (49.0 %) of the 49 patients tested; 58.3 % (14/24) in the VN/labyrinthitis group, 50 % (6/12) in the Meniere’s group, and 30.8 % (4/13) in the central group. HSN did not correlate with induction or modulation of the nystagmus by mastication (v2 test, p = 0.095). Vibration induced or modulated nystagmus in 19 (39.6 %) of the 48 patients tested; 56.5 % (13/23) in the VN/labyrinthitis group, 33.3 % (4/12) in the Meniere’s
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normal, excluding a significant asymmetry, while normal brain MRIs and MR angiography excluded a structural lesion or vascular steal phenomenon as a possible explanation for mastication-induced vertigo and nystagmus. We hypothesize that the development of vertigo and nystagmus during mastication indicates an unmasking of latent vestibular asymmetry by trigeminal stimulation (activation). Reciprocal connections between the vestibular and trigeminal systems
Fig. 4 Patterns of nystagmus modulation by mastication in the additional patients. a Most patients (27/33, 81.8 %) showed a gradual build-up of the nystagmus by mastication and gradual dissipation of the induced nystagmus after variable durations of plateau. b Five patients (5/33, 15.2 %) had a gradual suppression of the spontaneous nystagmus by mastication, which lasted even after cessation of the mastication. c Only a patient with acute VN showed a mild suppression of the spontaneous nystagmus during the mastication and a rather abrupt increase just after cessation of the mastication, which is also followed by a gradual decrease. The arrow in each figure indicates the duration of mastication
group, and 15.4 % (2/13) in the central group. The development of VIN did not correlate with induction of mastication-induced nystagmus, either (v2 test, p = 0.195).
Discussion Both index patients developed mastication-induced vertigo and nystagmus several months after near complete resolution of an episode consistent with acute unilateral vestibulopathy. In both subjects, the vertigo and nystagmus built up gradually during the mastication and dissipated slowly after cessation of the mastication. Interictal neurotological evaluations were
There are experimental evidences of reciprocal projections between the trigeminal sensory nucleus and vestibular nuclei/nucleus prepositus hypoglossi in rats [2, 11–14]. Neurons in the caudal part of the trigeminal mesencephalic nucleus project mainly to the medial, inferior, and lateral vestibular nuclei, and moderately to the peripheral part of the superior vestibular nuclei [12]. Also, trigeminal mesencephalic neurons project directly to the cerebellum, which is involved in the control and coordination of eye– head movements [15]. Individual neurons of the mesencephalic nucleus send collaterals to the vestibular nuclei and the vestibulo-cerebellum [12]. The direct primary projection from the mesencephalic nucleus to the MVN is known to convey proprioceptive information from the face and extraocular muscles [2, 16]. In another study, the trigeminovestibular projection was predominantly of mandibular origin [11]. There are direct mandibular [17] and secondary trigeminal afferents to the vestibular nuclei [18, 19]. Vestibular nuclei and nucleus prepositus hypoglossi also project to the trigeminal nucleus [20, 21]. The MVN appears to be the integration center for the trigeminal-vestibular interaction since most of the vestibular projections to the motor trigeminal nucleus originate from the MVN and nucleus prepositus hypoglossi [13, 14]. Trigeminal modulation of the vestibular activity in animals In guinea pigs, electrical stimulation of the trigeminal nerve and nociceptive cutaneous stimulation of the face modulate spontaneous activity of the vestibular neuron with a latency of 1.2–6.2 ms [22]. Also, inputs from the perioral whiskers (i.e., direction of their bending) may be used in determining heading in lower vertebrates and in non-human primates [23]. Accordingly, trigeminal stimulations may change the discharge rate or evoke rhythmic activity in the vestibular neuron [22]. However, the effects induced by trigeminal stimulation were usually shorter and weaker than those by labyrinthine stimulation. Accordingly, even though trigeminal stimulation per se cannot induce eye movements, it may modulate preexisting nystagmus [22]. Modulation of the vestibular nystagmus by trigeminal stimulation has long been recognized
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[24]. The trigeminal modulation of vestibular activity suggests a trigeminal role in the control of posture and orientation [22], and a vestibular role in the actuation and coordination of trigeminal reflexes [25–27]. The vestibular system by the way of its spinal and trigeminal projections may modulate the transmission of information from the neck as well as from the face [2, 28, 29]. In guinea pigs compensated from unilateral labyrinthectomy, unilateral trigeminal neurotomy increases the amplitude of vestibular field potentials recorded from intact vestibular nuclei [30]. Trigeminal neurotomy also induces vestibular decompensation in guinea pigs that were compensated from hemilabyrinthectomy, which results in reemergence of nystagmus, head torsion, curvature of the trunk, extension of the forelimb, circling and rolling movements, and impaired righting reflexes [31]. These signs of decompensation lasted for 6–8 h after trigeminal neurotomy. Trigeminal stimulation as well as unilateral trigeminal neurotomy may disclose latent vestibular nystagmus after hemilabyrinthectomy [31, 32]. In view of these findings, the trigeminal system appears to contribute to vestibular compensation by inhibiting the hyperactive vestibular nuclei on the intact side and by decreasing tonic commissural inhibitory influences on the deafferentiated vestibular nuclei [22]. Furthermore, microstimulation of the motor trigeminal nucleus induces nystagmus in anaesthetized rats (Dr. Deriu: unpublished observations).
Induction or modulation of nystagmus by mastication in vestibular disorders Our study indicates that trigeminal modulation of the vestibular system is a universal phenomenon in humans by demonstrating modulation of the nystagmus by mastication in patients with vestibulopathy of variable causes. While mastication did not induce nystagmus in normal controls, almost all the patients with SN showed modulation of SN by mastication. Furthermore, mastication induced nystagmus in five of 21 patients without SN. However, the patterns of modulation varied, and the mechanisms of these various modulations remain unknown. The modulation patterns may be related to the interval from symptom onset to evaluation. However, there were no differences in the interval among the groups with different patterns of modulation in both VN/labyrinthitis and central vestibular disorders. Of interest, three of the four patients with Meniere’s disease showed an augmentation of the SN with mastication during the paretic phase. However, the induced nystagmus in the Meniere’s patients without SN was either paretic or irritative. Otherwise, the modulation may have been affected by the side of predominant chewing, which could not be monitored in our study. Individual variations in the trigeminovestibular connection remain another possibility.
Trigeminal modulation of vestibular activity in humans
Characteristics and mechanism of mastication-induced vertigo and nystagmus
The modulation of vestibular nystagmus by trigeminal stimulation has long been known since the work by Lorente de No in rabbits [24]. In humans, however, there has been a paucity of data on trigeminovestibular modulation, even though several studies have documented the vestibular modulation of the trigeminal activities [33, 34]. In patients with migraine, painful trigeminal stimulation elicits nystagmus or generally increases pre-existing spontaneous nystagmus [35]. The evoked nystagmus has a mean latency of 25 s and a rather variable duration [35]. The nystagmus shows a linear slow phase and visual suppression, which suggests a vestibular nystagmus of peripheral origin [35]. These findings also indicate that trigeminal activation may induce an imbalance of the vestibular system in humans. One of our index patients developed migraines when she developed severe mastication-induced vertigo. She also showed a marked suppression of mastication-induced nystagmus by visual fixation and abnormal HIT only after developing mastication-induced nystagmus. These findings also suggest nystagmus of vestibular origin. These patients with migraines may be more susceptible to trigeminal modulation of the vestibular system.
Of interest, our index patients developed masticationinduced vertigo and nystagmus several months after an episode consistent with acute unilateral vestibulopathy. The near complete resolution of symptoms during the intervening periods indicates a compensation for the preceding unilateral vestibulopathy. It remains unclear why the mastication-induced vestibular imbalance developed several months after the remission of the acute symptoms. Otherwise, it may have been masked by acute symptoms. In our index patients, the nystagmus began to build up with a latency of several minutes after initiation of mastication, and gradually dissipated after discontinuation of mastication. These features are also characteristic of nystagmus induced by head-shaking, which is explained by asymmetrical vestibular input and central velocity storage mechanism [36]. The velocity storage mechanism contributes to an accumulation of the vestibular inputs during repetitive stimulation, which is known to be attained by the vestibular nuclei and the commissural fibers connecting them [37]. During mastication, the gradual accumulation of vestibular asymmetry due to decompensation may have been discharged as nystagmus in our patients.
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Unilateral vestibular hypofunction or asymmetric central vestibulopathy often leads to central vestibular asymmetry. In peripheral vestibulopathies, transient nystagmus often occurs after skull bone vibration or after head shaking due to unequal stimulation of the vestibular system between two sides. The nystagmus lateralizes to the abnormal side with hypofunction. The same principle may be applied during mastication. As we chew, more so in the case of crunchy and brittle food such as cucumber, high-frequency vibrations may be transmitted to the labyrinth via the jaw bones. These vibrations, when repeated over time due to constant chewing, can lead to asymmetric stimulation of the vestibular end organ and result in asymmetric build-up of tone in the vestibular nuclei in peripheral vestibulopathies, or asymmetric build-up of tone in the vestibular nuclei in central vestibulopathies. Such asymmetry then causes mastication-induced nystagmus. The rate at which nystagmus emerges would depend upon how rapidly the asymmetry develops between two sides, and dissipation of nystagmus after cessation of mastication would depend upon the decay TC of the vestibular velocity storage. However, our patients did not show any correlation between the VIN/HSN and the mastication-induced nystagmus. Otherwise, the latency may be related to the time required for the vasodilator effect to appear in rat facial skin after electrical stimulation of the trigeminal ganglion, an effect mediated by the release of calcitonin gene-related peptide (CGRP) [38]. Alternatively, trigeminal stimulus activates the efferent olivocochlear system through the connections between the trigeminal sensory and vestibular nuclei in the brainstem [11]. Acknowledgments The authors are grateful to Professor Thomas Brandt for his helpful comments in preparing this manuscript. This study was supported by a grant from the Korea Medical Devices Industrial Cooperative Association and the Small and Medium Business Administration (08-2011-065). Conflicts of interest Dr. Kim serves as an Associate Editor of Frontiers in Neuro-otology and on the editorial boards of the Journal of Korean Society of Clinical Neurophysiology, Research in Vestibular Science, Journal of Clinical Neurology, Frontiers in Neuroophthalmology, Journal of Neuro-ophthalmology, and Case Reports in Ophthalmological Medicine; he has received research support from SK Chemicals, Co. Ltd. SH Park, JW Koo, DU Kim, JT Kim, HJ Kim, Oh, Welgampola, and Deriu report no conflicts of interest.
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