Otology & Neurotology 36:865Y872 Ó 2015, Otology & Neurotology, Inc.
Head-shaking and Vibration-induced Nystagmus During and Between the Attacks of Unilateral Me´nie`re’s Disease *Sun-Uk Lee, †Hyun-Ju Kee, ‡Seung Soo Sheen, §Byung Yoon Choi, §Ja-Won Koo, and kJi-Soo Kim *Department of Neurology, Ajou University School of Medicine, Ajou University Hospital, Suwon; ÞKeimyung University School of Medicine, Daegu; þSection of Clinical Epidemiology & Biostatistics, Regional Clinical Trial Center, Ajou University School of Medicine, Suwon; §Department of OtolaryngologyYHead and Neck Surgery; and kDepartment of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
Objective: To aid in defining each phase of Me´nie`re’s disease (MD) and underlying vestibular pathophysiology by analyzing the evolving patterns of spontaneous, head-shaking (HSN), and vibration-induced nystagmus (VIN) during and between the attacks of MD. Study Design: Retrospective case series review. Methods: We analyzed the patterns of HSN and VIN during 123 attacks from 87 patients who had definite unilateral MD and underwent recording of eye movements both during and between the attacks using video-oculography. Results: HSN tended to beat toward the lesion side during the irritative phase (80.0%) and toward the healthy side during the paretic phase (82.9%). In contrast, VIN was more commonly
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Address correspondence and reprint requests to Ji-Soo Kim, M.D., Ph.D., Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 173-82 Gumiro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea; E-mail: [email protected] Financial Disclosure: This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020). S.U.L., H.J.K., S.S.S., B.Y.C., and J.W.K. report no conflicts of interest. J.S.K. serves as an Associate Editor of Frontiers in Neuro-otology and on the editorial boards of the Journal of Clinical Neurology, Frontiers in Neuro-ophthalmology, Journal of Neuro-ophthalmology, Journal of Vestibular Research, Journal of Neurology, and Medicine, and received research support from SK Chemicals, Co. Ltd. S.U.L. and H.J.K. equally contributed to this study. S.U.L. and H.J.K. wrote the article and analyzed and interpreted the data. S.S.S., B.Y.C., and J.W.K. analyzed and interpreted the data, and revised the article. J.S.K. conducted the design and conceptualization of the study, interpretation of the data, and drafting and revising the article. Supplemental digital content is available in the text.
Me´nie`re’s disease (MD) is characterized by recurrent spells of vertigo associated with tinnitus, aural fullness, and hearing loss (1). The attacks of MD have been ascribed to endolymphatic hydrops and consequent rupture of the membranous labyrinth (2Y4). According to this membrane rupture theory, leakage of the potassium-rich endolymph into the perilymph excites the first-order afferent nerve fibers (4). However, alternative theories include faulty drainage and consequent excess of the endolymph (5), and leakage of potassium through the tight junctions between the vestibular hair cells (6). During the attacks of MD, spontaneous nystagmus (SN) can be observed and change its direction over time (7). An irritative phase characterized by SN beating toward the involved ear is followed by a paretic phase characterized by SN beating toward the uninvolved ear (7). After the paretic phase, restoration of inputs from the peripheral vestibular apparatus in combination with central compensation may
induced during the irritative phase (63.7%) and more likely beat toward the healthy side irrespective of the phases evaluated (84.3%). Directional dissociation may occur between HSN and VIN, especially during the irritative phase when HSN mostly beat to the lesion side, but VIN is toward the healthy side. Conclusion: The characteristic patterns of HSN and VIN during each phase of MD would aid in defining the acute phases of MD and understanding the underlying vestibular pathophysiology. Key Words: Head-shaking nystagmusVMe´nie`re’s diseaseVVertigoVVibration-induced nystagmus.
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reverse the static vestibular imbalance to favor the affected ear and result in recovery nystagmus that beats toward the affected side (8). Even though the changes in direction of SN in MD have been well established in the literature, the patterns of provoked nystagmus during the various phases of an acute vertigo episode are still unknown (9Y13). Various maneuvers have been applied to assess the static or dynamic vestibular imbalances in MD, including headshaking (13), vibration stimuli (12,14), hyperventilation (15,16), and mastication (17). However, those studies were mostly limited by evaluation only during the interictal periods, and no study has attempted to define the evolution patterns of spontaneous and induced nystagmus in patients with MD. We hypothesized that determining the evolving patterns of spontaneous and induced nystagmus may aid in defining the acute phases and lead to better understanding of the vestibular pathophysiology during each phase of an acute vertigo attack in MD. PATIENTS AND METHODS Patients We initially reviewed the medical records of 235 patients who had a diagnosis of definite unilateral MD according to the 1995 AAO-HNS criteria (18) and had neurotological evaluation during the acute phase. The recruitment of the patients was performed using our database implemented in the Health Information System of Seoul National University Bundang Hospital, which included all MD patients seen at the Dizziness Clinic from June 2003 to July 2014. The acute phase was defined when the patients suffered from vertigo along with auditory symptoms, or within 1 day after the cease of vertigo only when the patients still showed abnormal SN, which will be defined later. The irritative phase was defined when the patients showed ipsilesional nystagmus whereas the paretic phase was determined when the nystagmus beat away from the lesion side. In contrast, the interictal phase was determined when the patients had no dizziness/vertigo or abnormal SN. The time gap between the acute and interictal phases was approximately 4 months (median = 139 d, interquartile range [IQR] = 22Y508 d). Patients with other neurological signs or history of other neurological or neurotological disorders were excluded. The affected side was determined with the side of auditory symptoms, including the hearing loss, tinnitus, and ear fullness, or with the side of objective hearing impairment on pure tone audiometry (18). After excluding 148 patients without video-oculographic recording of eye movements either during the acute (n = 46) or interictal phase (n = 61), bilateral caloric paresis (n = 12), previous auditory symptoms in the other ear (n = 11), combined positional nystagmus (n = 6), and vertical or torsional nystagmus stronger than horizontal one, either spontaneous or induced (n = 3), combined migrainous headache (n = 9), 87 patients were finally included for analyses. Because 18 patients had evaluation during more than one spell (54 attacks, 60 irritative and 63 paretic phases) of vertigo, we analyzed the findings of 123 attacks from 87 patients.
Neurotological Evaluation The neurotological examination included evaluation for SN, head-shaking nystagmus (HSN), vibration-induced nystagmus (VIN), and positional nystagmus (19).
Eye movements were recorded using video-oculography (SMI, Teltow, Germany or ICS Medical, Schaumburg, IL, USA). SN was recorded with and without fixation while sitting. The presence of abnormal SN was defined only when the SN was observed even during visual fixation or the slow phase velocity (SPV) of SN exceeded the values observed in normal controls (Q1.1 degrees/s) without fixation. Vibratory stimuli were applied to either mastoid for 10 seconds without visual fixation using VVIB 100 (Synapsys, Marseille, France). The frequency of the vibration was 100 Hz (T5%) and the contact area was 0.9 cm2. The stimuli were given for 10 seconds at each location with an interval of 5 seconds. Patients were instructed to look straight forward while the vibratory stimuli were applied. If the intensity of VIN were different between the sides, the stronger one was adopted for analyses (12). VIN was considered to be present only when the maximal SPV exceeded the values (mean T 2SD) observed in normal controls after subtracting the SPV of SN (20). HSN was induced by a passive head-shaking maneuver. While the patient was being seated upright without visual fixation, the examiner pitched the patient’s head approximately 30 degrees to bring the horizontal semicircular canals into the plane of stimulation. Then, the head was shaken in a sinusoidal manner for 15 seconds at the frequency of 2.8 Hz paced to the sound of a metronome. The presence of HSN was also determined only when the peak SPV of the nystagmus observed after the head shaking exceeded the normal values (mean T 2 SD) and when it lasted more than 5 seconds (21). If HSN had been biphasic, only the first phase was taken into account. To exclude the patients with positional nystagmus (22), patients were laid supine from sitting (lying-down nystagmus) and then turned to either side while in supine (head-turning nystagmus). After then, the patients were moved from a supine to sitting position with the head bent down (head-bending nystagmus). Also, they were subjected to left and right DixHallpike maneuvers and straight hanging test. Bithermal caloric tests were performed by irrigating the ears for 25 seconds with 150Y250 ml of cold and hot water (30 and 44 -C, respectively). Asymmetry of vestibular function was calculated using Jongkees’ formula. Canal paresis (CP) was defined as a response difference of 25% or more between the ears.
Statistical Analysis Statistical analyses were performed using SPSS (version 18.0; SPSS, Chicago, IL, USA). The nominal/independent variables were compared using binomial, W2 tests while the W2 tests whereas the nominal/dependent variables were compared using McNemar’s test. Continuous/independent variables were compared using independent t test and Mann-Whitney U test whereas continuous/dependent variables were compared using Wilcoxon singed rank test. Correlations between SPVs and CP were sought using Spearman’s correlation. A significance level was set at p less than 0.05.
RESULTS Patients had a mean age at 58.7 years without a difference between women and men (59.6 T 13.8 vs. 57.0 T 14.5, p = 0.419). The disease duration ranged from 1 week to 30 years (median = 22 mo). Each ear was equally involved (right/left = 43:44, p , 1.000). Evaluation was performed during 60 irritative and 63 paretic phases. The patients’ age (57.8 T 15.3 vs.
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NYSTAGMUS DURING ATTACKS OF ME´NIE`RE_S DISEASE
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FIG. 1. Head-shaking nystagmus (HSN). A, The prevalence and direction of HSN according to the phases. The HSN was more frequently observed during the acute phases than during the interictal periods (p e 0.001, McNemar’s test). During the interictal periods, HSN tended to beat to either side without a directional preponderance (p , 1.000, binomial test). In contrast, HSN mostly beat toward the lesion side during the irritative phase when observed (32/40, 80.0%, p G 0.001, binomial test) whereas it mostly beat away from the lesion side during the paretic phase (34/41, 82.9%, p G 0.001, binomial test). B, The slow phase velocity (SPV) of HSN differed between the interictal periods (range = j11.9Y10.0 degrees/s, median = 0, interquartile range [IQR] = j1.6Y0.6) and irritative phase (range = j27.0Y35.3 degrees/s, median = 3.1, IQR = j1.3Y6.0, p = 0.004, Wilcoxon signed rank test), and between the interictal periods and paretic phase (range = j31.5Y45.2 degrees/s, median = j3.3, IQR = j6.7Y0.7, p = 0.031, Wilcoxon signed rank test). For comparison, the SPV in the ipsilesional direction is coded being negative. Also for brevity, the extreme SPV values (910 degrees/s or Gj10 degrees/s) are not shown in this graph.
59.8 T 12.2, p = 0.523, independent t test), disease duration (median = 16 mo, IQR = 3Y60 vs. median = 24, IQR = 6Y66, p = 0.990, Mann-Whitney U test), and the degree of CP (median = 28%, IQR = 11Y39 vs. median = 26, IQR = 6Y51, p = 0.647, Mann-Whitney U test) did not differ
between the patients evaluated during the irritative and paretic phases. Bithermal caloric tests were performed during the interictal phase in 68 patients and showed ipsilesional CP in half of them (34/68, 50.0%). Otology & Neurotology, Vol. 36, No. 5, 2015
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FIG. 2. Vibration-induced nystagmus (VIN). A, The prevalence and direction of VIN according to the phases. VIN was more frequently observed during the irritative phase than during the interictal periods (p = 0.003, McNemar’s test). However, the prevalence of VIN did not differ between the paretic phase and interictal period (p = 0.052, McNemar’s test). VIN more likely beat toward the intact side when observed irrespective of the phases (binomial test). B, The SPVs of VIN did not differ among the phases observed (Wilcoxon signed rank test); the interictal periods (range = j14.1Y22.3 degrees/s, median = j1.7, IQR = j4.0Y0), the irritative phase (range = j21.2Y9.4 degrees/s, median = j5.1, IQR = j8.1Y1.0), and the paretic phase (range = j22.0Y5.8 degrees/s, median = j2.0, IQR = j6.2Y1.3). For comparison, the SPV in the ipsilesional direction is coded being negative. Also for brevity, the extreme SPV values (910 degrees/s or Gj10 degrees/s) are not shown in this graph.
Spontaneous Nystagmus During the irritative phase (n = 60), the SPV of ipsilesional nystagmus ranged from 1.2 to 22.0 degrees/s (median = 3.7, IQR = 1.6Y7.6) whereas that of contralesional nystagmus during the paretic phase (n = 63) ranged from 1.1 to 26.6
degrees/s (median = 2.8, IQR = 1.8Y4.6). The SPV did not differ among the patients evaluated during the irritative and paretic phases (p = 0.173, Mann-Whitney U test). Four patients had serial evaluation during the consecutive phases of an attack. In three of them, the paretic phase was
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NYSTAGMUS DURING ATTACKS OF ME´NIE`RE_S DISEASE TABLE 1.
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Comparison of clinical features according to the presence of directional dissociation between the head-shaking and vibration-induced nystagmus With Dissociation (n = 16)
Mean age (SD) Sex, women Median disease duration (IQR), mo Affected ear, right Mean caloric paresis (SD), %
57.3 (11.0) 12/16 (75.0%) 12.0 (0.5Y48) 9/16 (56.3%) 19 (17)
Without Dissociation (n = 70) 58.5 46/70 24.0 34/70 36
(14.4) (65.7%) (6Y54) (48.6%) (32)
P Value 0.757 0.565 0.392 0.579 0.012*
IQR, interquartile range; SD, standard deviation.
followed by recovery phase with ipsilesional nystagmus whereas the remaining patient showed an evolution from the irritative to paretic phase. Head-shaking Nystagmus We measured HSN during 123 attacks (60 irritative and 63 paretic phases) and 109 interictal periods in 87 patients. In eight patients, the HSN was evaluated both during the irritative and paretic phases. Overall, HSN was observed during 33 interictal periods (33/109, 30.3%), 40 irritative phases (40/60, 66.7%), and 41 paretic phases (41/63, 65.1%). The HSN was more frequently observed during the acute phases than during the interictal periods (p e 0.001, McNemar’s test; Fig. 1A). During the interictal periods, the direction of HSN was either to the healthy side or to the lesion side without a directional preponderance (p , 1.000, binomial test). However, HSN mostly beat toward the lesion side during the irritative phases (32/40, 80.0%, p G 0.001, binomial test) whereas it mostly beat toward the intact side during the paretic phases (34/41, 82.9%, p G 0.001, binomial test). The SPVs of HSN were higher during the acute phases than during the interictal periods (irritative vs. interictal, p = 0.004; paretic vs. interictal, p = 0.031, Wilcoxon signed rank test, Fig. 1B). The SPVs of HSN during the interictal periods showed a correlation with the degree of CP (r2 = j0.249, p = 0.041, Spearman’s correlation). However, no correlation was found between the degree of CP and intensity of HSN during the irritative (r2 = j0.078, p = 0.650, Spearman’s correlation) or paretic phases (r2 = j0.181, p = 0.271, Spearman’s correlation). Vibration-induced Nystagmus We evaluated VIN during 111 attacks (55 irritative and 56 paretic phases) and 104 interictal periods. Eight patients had an evaluation of VIN both during the irritative and paretic phases. The VIN was observed during 29 interictal periods (29/104, 27.9%), 35 irritative phases (35/55, 63.6%), and 25 paretic phases (25/56, 44.6%). The VIN was more frequently observed during the irritative phases than during the interictal periods (p = 0.003, McNemar’s test, Fig. 2A). However, the prevalence of VIN did not differ between the paretic phases and interictal periods (p = 0.052, McNemar’s test). In contrast to HSN, VIN more likely beat toward the intact side when observed irrespective of the phases (75/ 89, 84.3%, Fig. 2A). The SPVs of VIN did not differ among the phases observed (Fig. 2B). Likewise in HSN, a
significant correlation was observed between the degree of CP and the SPVs of VIN during the interictal phase (r2 = j0.496, p G 0.001, Spearman’s correlation), but no correlations were found between the degree of CP and intensity of VIN during the attacks. Directional Dissociations Between the HSN and VIN VIN and HSN beat in the opposite directions in six occasions during the interictal periods (6/102, 5.9%), 21 occasions during the irritative phases (21/55, 38.2%; Video, Supplemental Digital Content 1, http://links.lww.com/MAO/A296), and five occasions during the paretic phases (5/56, 8.9%). One patient showed a directional dissociation between VIN and HSN all through the interictal, irritative, and paretic phases. The directional dissociation between HSN and VIN was more common during the irritative phase than during the paretic (p G 0.001, W2 test) or the interictal period (p G 0.001, McNemar’s test). No differences were found in the clinical variables between the groups with and without this directional dissociation except the caloric asymmetry (Table 1), which was significantly less in patients with a dissociation than without (mean T SD, 19 T 17% vs. 36 T 32%, p = 0.012, independent t test). Patterns of HSN and VIN During Multiple Different Attacks in a Patient We analyzed the patterns of SN, HSN, and VIN during the same phases of multiple different spells (26 irritative and 18 paretic phases) of vertigo in 13 of the 18 patients with multiple spells after excluding five patients who had evaluation only during different phases (two spells, but with an irritative phase during one attack and with a paretic phase during the other attack). Most (10/13, 76.9%) of them showed consistent patterns of HSN and VIN during the same phases of different spells, but three of them exhibited dissimilar features among different attacks. In a patient who had evaluation during two different paretic phases, the direction of HSN was ipsilesional during a spell, but contralesional during the other spell whereas the direction of VIN was consistently contralesional. In another patient with evaluation during two different irritative spells, HSN was ipsilesional during one attack, but absent during the other spell whereas VIN was not elicited during both spells. The remaining patient showed contralesional HSN and VIN during one paretic spell, but no HSN or VIN during the other spell. Thus, even in the three patients with different patterns of HSN and VIN during the same Otology & Neurotology, Vol. 36, No. 5, 2015
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phase of different spells, only one showed HSN in the opposite direction. DISCUSSION In this study, we describe patterns of HSN and VIN in unilateral definite MD during the various phases of an acute episode of vertigo. The findings in this study may be summarized as follows: 1) HSN tended to follow the direction of SN, beating toward the lesion side during the irritative phases and toward the healthy side during the paretic phases. 2) VIN was more commonly induced during the irritative phases and more likely beat toward the healthy side throughout the interictal, irritative, and paretic phases. 3) Directional dissociation may occur between the HSN and VIN, especially during the irritative phases when HSN mostly occurs in the direction of SN, but VIN was frequently induced in the opposite direction of SN. The characteristic patterns of HSN and VIN were well replicated in patients with evaluations during multiple different attacks, which support a consistent mechanism in generating HSN and VIN during each phase of MD. Spontaneous Nystagmus During the attacks of MD, evolution of underlying vestibular imbalance and resultant changes in the nystagmus direction have been subject to debate in the literature (7,8,23). We defined the irritative and paretic phases based on the direction of SN during the attacks of MD. Given that the ipsilesional nystagmus may occur during the recovery as well as irritative phase, the irritative phase defined in our study comprised both initial irritative phase and the recovery phase after the paretic phase. Indeed, three of the four patients with serial evaluation during consecutive phases of a Me´nie`re attack showed an evolution from the paretic phase (contralesional nystagmus) into the recovery phase (ipsilesional nystagmus). Thus, it would be possible to characterize the difference in the patterns of induced nystagmus between the irritative and recovery phases only with serial evaluation throughout an attack in a larger number of patients. Head-shaking Nystagmus HSN has been ascribed to asymmetrical peripheral vestibular inputs and amplification of them by the velocity storage mechanism (1). In this study, horizontal head-shaking tended to augment the SN during both irritative and paretic phases. Thus, the patterns of HSN are consistent with the proposition based on asymmetric activities of the peripheral vestibular structures during the attacks. During the irritative phase, the vestibular inputs from the affected ear may surpass those from the healthy ear and thereby inducing HSN beating to the affected side. In contrast, the opposite would happen during the paretic phases. During the interictal periods, the SPV of HSN correlated well with the degree of CP. Patients with more severe CP were more likely to show greater contralesional
HSN. Unlike a previous study that also investigated a correlation between the degree of CP and intensity of HSN (12), our study showed that HSN can represent the remnant vestibular reservoir in the affected ear during the follow-up of unilateral MD. Of interest, HSN occurred in the opposite direction of SN in 13.3% of occasions during the irritative phase and in 11.1% during the paretic phase. Development of HSN in the opposite direction of SN has previously been reported in lateral medullary (LMI) and cerebellar infarctions (21,24,25) and has been considered one of the central patterns of HSN. In LMI and cerebellar infarctions, the HSN beating to the lesion side has been explained by ipsilesional disinhibition of the velocity storage mechanism by damaging the fibers from the nodulus and ventral uvula to the vestibular nuclei (21). However, given the occasional dissociations in the direction of SN and HSN during the acute phases of unilateral MD, the clinical implication of HSN in the opposite direction of SN should be interpreted with caution in the context of accompanying symptoms and signs. Although the horizontal direction of HSN did not change over time in most patients with LMI (10/11, 90.9%) (21), the HSN in the opposite direction of SN showed a resolution or direction reversal over time in most of our patients with unilateral MD. These findings also indicate that the static vestibular imbalance is not always in accordance with the dynamic one during the acute phases of MD. Vibration-induced Nystagmus Vibratory stimuli applied either to the mastoids, forehead, or even to the neck muscles may induce nystagmus in patients with peripheral (12,26,27) or central vestibulopathies (21). Because of simultaneous stimulation of the vestibular receptors on both sides during the vibratory stimuli, VIN is considered to represent asymmetrical peripheral vestibular input in peripheral vestibular disorders. In our patients, VIN beat mostly toward the healthy ear side when observed, irrespective of the phases when the evaluation was performed. These findings are consistent with those reported in the previous studies (12,13,28). In contrast to head-shaking, vibration is known to induce nystagmus by stimulating both vestibular organs directly (28). Given the predominant contralesional VIN irrespective of the phases evaluated, relative hypofunction of the ipsilesional hair cells involved in the generation of VIN appears to be maintained throughout the phases of MD. In a previous study performed during the interictal periods of MD by the authors, the direction of VIN correlated well with the severity of CP, and contralesional VIN was more likely to occur in patients with more severe CP (12). This correlation was also replicated in the current study and suggests that VIN is more related to the excitability of Type II hair cells that are rather selectively destroyed in MD (12). However, the correlation between the direction of ictal VIN and severity of interictal CP was insignificant. We assume that factors other than interictal CP may be involved in determining the direction of VIN during the acute phases of MD.
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NYSTAGMUS DURING ATTACKS OF ME´NIE`RE_S DISEASE Of interest, the proportion of contralesional VIN increased during the irritative phase. Because the static vestibular inputs from the affected ear would be larger than those from the healthy ear during the irritative phases, the underlying vestibular imbalance may have been reversed during the vibratory stimuli, possibly as a result of stimulation of the intact Type II hair cells in the healthy ear. Directional Dissociation Between HSN and VIN In our study, directional dissociation of HSN and VIN was observed in 32 of the total 213 occasions (15.0%) and was especially more common during the irritative phases (21/55, 38.2%). This directional dissociation has also been described in MD (13,28) as well as in other disorders including LMI (21), vestibular neuritis (29), and RamsayHunt syndrome (29). The proportion of this dissociation observed in this study seems to be somewhat lower than that reported previously in MD (18.1Y65.0%) (13,28). This discrepancy may be explained by different stimulation methods and positive criteria, dissimilar proportion of the phases when the evaluation was performed, or different proportion of disease stages. The directional dissociation between VIN and HSN may reflect different mechanisms involved in generation of each nystagmus. Although HSN is generally believed to represent the vestibular imbalance accumulated in the central velocity storage system, the VIN seems to represent an asymmetry in the excitability of the peripheral vestibular apparatus (30). Given the instant onset and offset nature of VIN, the velocity storage system seems to contribute little, if any, to generation of VIN. Furthermore, one labyrinth is stimulated whereas the other is inhibited during horizontal head-shaking (push-and-pull effect), but vibration stimulates both labyrinth simultaneously (28). The different frequency of stimuli during head-shaking and vibration may be another explanation for this discrepancy. Patients with MD show a selective loss of Type II hair cells in the vestibular end organs (31). Indeed, patients with MD frequently exhibit normal gain of the VOR during head impulse tests in the presence of severe CP (11). This indicates that the remaining hair cells respond differently according to the stimulation frequency in MD. The different vestibular compensation according to stimulation frequency may also contribute to this directional dissociation (32). In our study, the prevalence of this directional dissociation differed from phase to phase, most common during the irritative phase. This was mostly caused by the increased proportion of ipsilesional HSN during the irritative phase. The increased prevalence of ipsilesional HSN seems plausible given that HSN is initiated by asymmetric peripheral vestibular inputs in peripheral vestibular disorders. The pattern of directional dissociation between HSN and VIN observed in our patients with MD is dissimilar to that reported in LMI (21) in which the VIN beat in the direction of SN whereas the HSN beat almost always toward the lesion side. In LMI, the consistent ipsilesional
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HSN was ascribed to asymmetric disinhibition of the velocity storage system (21).
CONCLUSION The characteristic findings of HSN and VIN during each phase of MD would aid in defining the acute phases of MD and understanding the underlying pathomechanisms.
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20. Choi KD, Oh SY, Kim HJ, Koo JW, Cho BM, Kim JS. Recovery of vestibular imbalances after vestibular neuritis. Laryngoscope 2007;117:1307Y12. 21. Choi KD, Oh SY, Park SH, Kim JH, Koo JW, Kim JS. Headshaking nystagmus in lateral medullary infarction: patterns and possible mechanisms. Neurology 2007;68:1337Y44. 22. Kim JS, Oh SY, Lee SH, et al. Randomized clinical trial for apogeotropic horizontal canal benign paroxysmal positional vertigo. Neurology 2012;78:159Y66. 23. Andrews JC, Honrubia V. Vestibular function in experimental endolymphatic hydrops. Laryngoscope 1988;98:479Y85. 24. Huh YE, Kim JS. Patterns of spontaneous and head-shaking nystagmus in cerebellar infarction: imaging correlations. Brain 2011;134:3662Y71. 25. Huh YE, Koo JW, Lee H, Kim JS. Head-shaking aids in the diagnosis of acute audiovestibular loss due to anterior inferior cerebellar artery infarction. Audio Neurootol 2013;18:114Y24. 26. Ohki M, Murofushi T, Nakahara H, Sugasawa K. Vibration-induced nystagmus in patients with vestibular disorders. Otolaryngol Head Neck Surg 2003;129:255Y8.
27. Goodwin GM, McCloskey DI, Matthews PB. Proprioceptive illusions induced by muscle vibration: contribution by muscle spindles to perception? Science 1972;175:1382Y4. 28. Dumas G, Karkas A, Perrin P, Chahine K, Schmerber S. Highfrequency skull vibration-induced nystagmus test in partial vestibular lesions. Otol Neurotol 2011;32:1291Y301. 29. Koo JW, Kim JS, Hong SK. Vibration-induced nystagmus after acute peripheral vestibular loss: comparative study with other vestibule-ocular reflex tests in the yaw plane. Otol Neurotol 2011;32:466Y71. 30. Park H, Hong SC, Shin J. Clinical significance of vibration-induced nystagmus and head-shaking nystagmus through follow-up examinations in patients with vestibular neuritis. Otol Neurotol 2008;29:375Y9. 31. Merchant SN. A method for quantitative assessment of vestibular otopathology. Laryngoscope 1999;109:1560Y9. 32. Lasker DM, Hullar TE, Minor LB. Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. III. Responses after labyrinthectomy. J Neurophysiol 2000;83:2482Y96.
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Head-shaking and Vibration-induced Nystagmus During and Between the Attacks of Unilateral Me´nie`re’s Disease *Sun-Uk Lee, †Hyun-Ju Kee, ‡Seung Soo Sheen, §Byung Yoon Choi, §Ja-Won Koo, and kJi-Soo Kim *Department of Neurology, Ajou University School of Medicine, Ajou University Hospital, Suwon; ÞKeimyung University School of Medicine, Daegu; þSection of Clinical Epidemiology & Biostatistics, Regional Clinical Trial Center, Ajou University School of Medicine, Suwon; §Department of OtolaryngologyYHead and Neck Surgery; and kDepartment of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
Objective: To aid in defining each phase of Me´nie`re’s disease (MD) and underlying vestibular pathophysiology by analyzing the evolving patterns of spontaneous, head-shaking (HSN), and vibration-induced nystagmus (VIN) during and between the attacks of MD. Study Design: Retrospective case series review. Methods: We analyzed the patterns of HSN and VIN during 123 attacks from 87 patients who had definite unilateral MD and underwent recording of eye movements both during and between the attacks using video-oculography. Results: HSN tended to beat toward the lesion side during the irritative phase (80.0%) and toward the healthy side during the paretic phase (82.9%). In contrast, VIN was more commonly
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Address correspondence and reprint requests to Ji-Soo Kim, M.D., Ph.D., Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 173-82 Gumiro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea; E-mail: [email protected] Financial Disclosure: This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020). S.U.L., H.J.K., S.S.S., B.Y.C., and J.W.K. report no conflicts of interest. J.S.K. serves as an Associate Editor of Frontiers in Neuro-otology and on the editorial boards of the Journal of Clinical Neurology, Frontiers in Neuro-ophthalmology, Journal of Neuro-ophthalmology, Journal of Vestibular Research, Journal of Neurology, and Medicine, and received research support from SK Chemicals, Co. Ltd. S.U.L. and H.J.K. equally contributed to this study. S.U.L. and H.J.K. wrote the article and analyzed and interpreted the data. S.S.S., B.Y.C., and J.W.K. analyzed and interpreted the data, and revised the article. J.S.K. conducted the design and conceptualization of the study, interpretation of the data, and drafting and revising the article. Supplemental digital content is available in the text.
Me´nie`re’s disease (MD) is characterized by recurrent spells of vertigo associated with tinnitus, aural fullness, and hearing loss (1). The attacks of MD have been ascribed to endolymphatic hydrops and consequent rupture of the membranous labyrinth (2Y4). According to this membrane rupture theory, leakage of the potassium-rich endolymph into the perilymph excites the first-order afferent nerve fibers (4). However, alternative theories include faulty drainage and consequent excess of the endolymph (5), and leakage of potassium through the tight junctions between the vestibular hair cells (6). During the attacks of MD, spontaneous nystagmus (SN) can be observed and change its direction over time (7). An irritative phase characterized by SN beating toward the involved ear is followed by a paretic phase characterized by SN beating toward the uninvolved ear (7). After the paretic phase, restoration of inputs from the peripheral vestibular apparatus in combination with central compensation may
induced during the irritative phase (63.7%) and more likely beat toward the healthy side irrespective of the phases evaluated (84.3%). Directional dissociation may occur between HSN and VIN, especially during the irritative phase when HSN mostly beat to the lesion side, but VIN is toward the healthy side. Conclusion: The characteristic patterns of HSN and VIN during each phase of MD would aid in defining the acute phases of MD and understanding the underlying vestibular pathophysiology. Key Words: Head-shaking nystagmusVMe´nie`re’s diseaseVVertigoVVibration-induced nystagmus.
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reverse the static vestibular imbalance to favor the affected ear and result in recovery nystagmus that beats toward the affected side (8). Even though the changes in direction of SN in MD have been well established in the literature, the patterns of provoked nystagmus during the various phases of an acute vertigo episode are still unknown (9Y13). Various maneuvers have been applied to assess the static or dynamic vestibular imbalances in MD, including headshaking (13), vibration stimuli (12,14), hyperventilation (15,16), and mastication (17). However, those studies were mostly limited by evaluation only during the interictal periods, and no study has attempted to define the evolution patterns of spontaneous and induced nystagmus in patients with MD. We hypothesized that determining the evolving patterns of spontaneous and induced nystagmus may aid in defining the acute phases and lead to better understanding of the vestibular pathophysiology during each phase of an acute vertigo attack in MD. PATIENTS AND METHODS Patients We initially reviewed the medical records of 235 patients who had a diagnosis of definite unilateral MD according to the 1995 AAO-HNS criteria (18) and had neurotological evaluation during the acute phase. The recruitment of the patients was performed using our database implemented in the Health Information System of Seoul National University Bundang Hospital, which included all MD patients seen at the Dizziness Clinic from June 2003 to July 2014. The acute phase was defined when the patients suffered from vertigo along with auditory symptoms, or within 1 day after the cease of vertigo only when the patients still showed abnormal SN, which will be defined later. The irritative phase was defined when the patients showed ipsilesional nystagmus whereas the paretic phase was determined when the nystagmus beat away from the lesion side. In contrast, the interictal phase was determined when the patients had no dizziness/vertigo or abnormal SN. The time gap between the acute and interictal phases was approximately 4 months (median = 139 d, interquartile range [IQR] = 22Y508 d). Patients with other neurological signs or history of other neurological or neurotological disorders were excluded. The affected side was determined with the side of auditory symptoms, including the hearing loss, tinnitus, and ear fullness, or with the side of objective hearing impairment on pure tone audiometry (18). After excluding 148 patients without video-oculographic recording of eye movements either during the acute (n = 46) or interictal phase (n = 61), bilateral caloric paresis (n = 12), previous auditory symptoms in the other ear (n = 11), combined positional nystagmus (n = 6), and vertical or torsional nystagmus stronger than horizontal one, either spontaneous or induced (n = 3), combined migrainous headache (n = 9), 87 patients were finally included for analyses. Because 18 patients had evaluation during more than one spell (54 attacks, 60 irritative and 63 paretic phases) of vertigo, we analyzed the findings of 123 attacks from 87 patients.
Neurotological Evaluation The neurotological examination included evaluation for SN, head-shaking nystagmus (HSN), vibration-induced nystagmus (VIN), and positional nystagmus (19).
Eye movements were recorded using video-oculography (SMI, Teltow, Germany or ICS Medical, Schaumburg, IL, USA). SN was recorded with and without fixation while sitting. The presence of abnormal SN was defined only when the SN was observed even during visual fixation or the slow phase velocity (SPV) of SN exceeded the values observed in normal controls (Q1.1 degrees/s) without fixation. Vibratory stimuli were applied to either mastoid for 10 seconds without visual fixation using VVIB 100 (Synapsys, Marseille, France). The frequency of the vibration was 100 Hz (T5%) and the contact area was 0.9 cm2. The stimuli were given for 10 seconds at each location with an interval of 5 seconds. Patients were instructed to look straight forward while the vibratory stimuli were applied. If the intensity of VIN were different between the sides, the stronger one was adopted for analyses (12). VIN was considered to be present only when the maximal SPV exceeded the values (mean T 2SD) observed in normal controls after subtracting the SPV of SN (20). HSN was induced by a passive head-shaking maneuver. While the patient was being seated upright without visual fixation, the examiner pitched the patient’s head approximately 30 degrees to bring the horizontal semicircular canals into the plane of stimulation. Then, the head was shaken in a sinusoidal manner for 15 seconds at the frequency of 2.8 Hz paced to the sound of a metronome. The presence of HSN was also determined only when the peak SPV of the nystagmus observed after the head shaking exceeded the normal values (mean T 2 SD) and when it lasted more than 5 seconds (21). If HSN had been biphasic, only the first phase was taken into account. To exclude the patients with positional nystagmus (22), patients were laid supine from sitting (lying-down nystagmus) and then turned to either side while in supine (head-turning nystagmus). After then, the patients were moved from a supine to sitting position with the head bent down (head-bending nystagmus). Also, they were subjected to left and right DixHallpike maneuvers and straight hanging test. Bithermal caloric tests were performed by irrigating the ears for 25 seconds with 150Y250 ml of cold and hot water (30 and 44 -C, respectively). Asymmetry of vestibular function was calculated using Jongkees’ formula. Canal paresis (CP) was defined as a response difference of 25% or more between the ears.
Statistical Analysis Statistical analyses were performed using SPSS (version 18.0; SPSS, Chicago, IL, USA). The nominal/independent variables were compared using binomial, W2 tests while the W2 tests whereas the nominal/dependent variables were compared using McNemar’s test. Continuous/independent variables were compared using independent t test and Mann-Whitney U test whereas continuous/dependent variables were compared using Wilcoxon singed rank test. Correlations between SPVs and CP were sought using Spearman’s correlation. A significance level was set at p less than 0.05.
RESULTS Patients had a mean age at 58.7 years without a difference between women and men (59.6 T 13.8 vs. 57.0 T 14.5, p = 0.419). The disease duration ranged from 1 week to 30 years (median = 22 mo). Each ear was equally involved (right/left = 43:44, p , 1.000). Evaluation was performed during 60 irritative and 63 paretic phases. The patients’ age (57.8 T 15.3 vs.
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FIG. 1. Head-shaking nystagmus (HSN). A, The prevalence and direction of HSN according to the phases. The HSN was more frequently observed during the acute phases than during the interictal periods (p e 0.001, McNemar’s test). During the interictal periods, HSN tended to beat to either side without a directional preponderance (p , 1.000, binomial test). In contrast, HSN mostly beat toward the lesion side during the irritative phase when observed (32/40, 80.0%, p G 0.001, binomial test) whereas it mostly beat away from the lesion side during the paretic phase (34/41, 82.9%, p G 0.001, binomial test). B, The slow phase velocity (SPV) of HSN differed between the interictal periods (range = j11.9Y10.0 degrees/s, median = 0, interquartile range [IQR] = j1.6Y0.6) and irritative phase (range = j27.0Y35.3 degrees/s, median = 3.1, IQR = j1.3Y6.0, p = 0.004, Wilcoxon signed rank test), and between the interictal periods and paretic phase (range = j31.5Y45.2 degrees/s, median = j3.3, IQR = j6.7Y0.7, p = 0.031, Wilcoxon signed rank test). For comparison, the SPV in the ipsilesional direction is coded being negative. Also for brevity, the extreme SPV values (910 degrees/s or Gj10 degrees/s) are not shown in this graph.
59.8 T 12.2, p = 0.523, independent t test), disease duration (median = 16 mo, IQR = 3Y60 vs. median = 24, IQR = 6Y66, p = 0.990, Mann-Whitney U test), and the degree of CP (median = 28%, IQR = 11Y39 vs. median = 26, IQR = 6Y51, p = 0.647, Mann-Whitney U test) did not differ
between the patients evaluated during the irritative and paretic phases. Bithermal caloric tests were performed during the interictal phase in 68 patients and showed ipsilesional CP in half of them (34/68, 50.0%). Otology & Neurotology, Vol. 36, No. 5, 2015
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FIG. 2. Vibration-induced nystagmus (VIN). A, The prevalence and direction of VIN according to the phases. VIN was more frequently observed during the irritative phase than during the interictal periods (p = 0.003, McNemar’s test). However, the prevalence of VIN did not differ between the paretic phase and interictal period (p = 0.052, McNemar’s test). VIN more likely beat toward the intact side when observed irrespective of the phases (binomial test). B, The SPVs of VIN did not differ among the phases observed (Wilcoxon signed rank test); the interictal periods (range = j14.1Y22.3 degrees/s, median = j1.7, IQR = j4.0Y0), the irritative phase (range = j21.2Y9.4 degrees/s, median = j5.1, IQR = j8.1Y1.0), and the paretic phase (range = j22.0Y5.8 degrees/s, median = j2.0, IQR = j6.2Y1.3). For comparison, the SPV in the ipsilesional direction is coded being negative. Also for brevity, the extreme SPV values (910 degrees/s or Gj10 degrees/s) are not shown in this graph.
Spontaneous Nystagmus During the irritative phase (n = 60), the SPV of ipsilesional nystagmus ranged from 1.2 to 22.0 degrees/s (median = 3.7, IQR = 1.6Y7.6) whereas that of contralesional nystagmus during the paretic phase (n = 63) ranged from 1.1 to 26.6
degrees/s (median = 2.8, IQR = 1.8Y4.6). The SPV did not differ among the patients evaluated during the irritative and paretic phases (p = 0.173, Mann-Whitney U test). Four patients had serial evaluation during the consecutive phases of an attack. In three of them, the paretic phase was
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NYSTAGMUS DURING ATTACKS OF ME´NIE`RE_S DISEASE TABLE 1.
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Comparison of clinical features according to the presence of directional dissociation between the head-shaking and vibration-induced nystagmus With Dissociation (n = 16)
Mean age (SD) Sex, women Median disease duration (IQR), mo Affected ear, right Mean caloric paresis (SD), %
57.3 (11.0) 12/16 (75.0%) 12.0 (0.5Y48) 9/16 (56.3%) 19 (17)
Without Dissociation (n = 70) 58.5 46/70 24.0 34/70 36
(14.4) (65.7%) (6Y54) (48.6%) (32)
P Value 0.757 0.565 0.392 0.579 0.012*
IQR, interquartile range; SD, standard deviation.
followed by recovery phase with ipsilesional nystagmus whereas the remaining patient showed an evolution from the irritative to paretic phase. Head-shaking Nystagmus We measured HSN during 123 attacks (60 irritative and 63 paretic phases) and 109 interictal periods in 87 patients. In eight patients, the HSN was evaluated both during the irritative and paretic phases. Overall, HSN was observed during 33 interictal periods (33/109, 30.3%), 40 irritative phases (40/60, 66.7%), and 41 paretic phases (41/63, 65.1%). The HSN was more frequently observed during the acute phases than during the interictal periods (p e 0.001, McNemar’s test; Fig. 1A). During the interictal periods, the direction of HSN was either to the healthy side or to the lesion side without a directional preponderance (p , 1.000, binomial test). However, HSN mostly beat toward the lesion side during the irritative phases (32/40, 80.0%, p G 0.001, binomial test) whereas it mostly beat toward the intact side during the paretic phases (34/41, 82.9%, p G 0.001, binomial test). The SPVs of HSN were higher during the acute phases than during the interictal periods (irritative vs. interictal, p = 0.004; paretic vs. interictal, p = 0.031, Wilcoxon signed rank test, Fig. 1B). The SPVs of HSN during the interictal periods showed a correlation with the degree of CP (r2 = j0.249, p = 0.041, Spearman’s correlation). However, no correlation was found between the degree of CP and intensity of HSN during the irritative (r2 = j0.078, p = 0.650, Spearman’s correlation) or paretic phases (r2 = j0.181, p = 0.271, Spearman’s correlation). Vibration-induced Nystagmus We evaluated VIN during 111 attacks (55 irritative and 56 paretic phases) and 104 interictal periods. Eight patients had an evaluation of VIN both during the irritative and paretic phases. The VIN was observed during 29 interictal periods (29/104, 27.9%), 35 irritative phases (35/55, 63.6%), and 25 paretic phases (25/56, 44.6%). The VIN was more frequently observed during the irritative phases than during the interictal periods (p = 0.003, McNemar’s test, Fig. 2A). However, the prevalence of VIN did not differ between the paretic phases and interictal periods (p = 0.052, McNemar’s test). In contrast to HSN, VIN more likely beat toward the intact side when observed irrespective of the phases (75/ 89, 84.3%, Fig. 2A). The SPVs of VIN did not differ among the phases observed (Fig. 2B). Likewise in HSN, a
significant correlation was observed between the degree of CP and the SPVs of VIN during the interictal phase (r2 = j0.496, p G 0.001, Spearman’s correlation), but no correlations were found between the degree of CP and intensity of VIN during the attacks. Directional Dissociations Between the HSN and VIN VIN and HSN beat in the opposite directions in six occasions during the interictal periods (6/102, 5.9%), 21 occasions during the irritative phases (21/55, 38.2%; Video, Supplemental Digital Content 1, http://links.lww.com/MAO/A296), and five occasions during the paretic phases (5/56, 8.9%). One patient showed a directional dissociation between VIN and HSN all through the interictal, irritative, and paretic phases. The directional dissociation between HSN and VIN was more common during the irritative phase than during the paretic (p G 0.001, W2 test) or the interictal period (p G 0.001, McNemar’s test). No differences were found in the clinical variables between the groups with and without this directional dissociation except the caloric asymmetry (Table 1), which was significantly less in patients with a dissociation than without (mean T SD, 19 T 17% vs. 36 T 32%, p = 0.012, independent t test). Patterns of HSN and VIN During Multiple Different Attacks in a Patient We analyzed the patterns of SN, HSN, and VIN during the same phases of multiple different spells (26 irritative and 18 paretic phases) of vertigo in 13 of the 18 patients with multiple spells after excluding five patients who had evaluation only during different phases (two spells, but with an irritative phase during one attack and with a paretic phase during the other attack). Most (10/13, 76.9%) of them showed consistent patterns of HSN and VIN during the same phases of different spells, but three of them exhibited dissimilar features among different attacks. In a patient who had evaluation during two different paretic phases, the direction of HSN was ipsilesional during a spell, but contralesional during the other spell whereas the direction of VIN was consistently contralesional. In another patient with evaluation during two different irritative spells, HSN was ipsilesional during one attack, but absent during the other spell whereas VIN was not elicited during both spells. The remaining patient showed contralesional HSN and VIN during one paretic spell, but no HSN or VIN during the other spell. Thus, even in the three patients with different patterns of HSN and VIN during the same Otology & Neurotology, Vol. 36, No. 5, 2015
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phase of different spells, only one showed HSN in the opposite direction. DISCUSSION In this study, we describe patterns of HSN and VIN in unilateral definite MD during the various phases of an acute episode of vertigo. The findings in this study may be summarized as follows: 1) HSN tended to follow the direction of SN, beating toward the lesion side during the irritative phases and toward the healthy side during the paretic phases. 2) VIN was more commonly induced during the irritative phases and more likely beat toward the healthy side throughout the interictal, irritative, and paretic phases. 3) Directional dissociation may occur between the HSN and VIN, especially during the irritative phases when HSN mostly occurs in the direction of SN, but VIN was frequently induced in the opposite direction of SN. The characteristic patterns of HSN and VIN were well replicated in patients with evaluations during multiple different attacks, which support a consistent mechanism in generating HSN and VIN during each phase of MD. Spontaneous Nystagmus During the attacks of MD, evolution of underlying vestibular imbalance and resultant changes in the nystagmus direction have been subject to debate in the literature (7,8,23). We defined the irritative and paretic phases based on the direction of SN during the attacks of MD. Given that the ipsilesional nystagmus may occur during the recovery as well as irritative phase, the irritative phase defined in our study comprised both initial irritative phase and the recovery phase after the paretic phase. Indeed, three of the four patients with serial evaluation during consecutive phases of a Me´nie`re attack showed an evolution from the paretic phase (contralesional nystagmus) into the recovery phase (ipsilesional nystagmus). Thus, it would be possible to characterize the difference in the patterns of induced nystagmus between the irritative and recovery phases only with serial evaluation throughout an attack in a larger number of patients. Head-shaking Nystagmus HSN has been ascribed to asymmetrical peripheral vestibular inputs and amplification of them by the velocity storage mechanism (1). In this study, horizontal head-shaking tended to augment the SN during both irritative and paretic phases. Thus, the patterns of HSN are consistent with the proposition based on asymmetric activities of the peripheral vestibular structures during the attacks. During the irritative phase, the vestibular inputs from the affected ear may surpass those from the healthy ear and thereby inducing HSN beating to the affected side. In contrast, the opposite would happen during the paretic phases. During the interictal periods, the SPV of HSN correlated well with the degree of CP. Patients with more severe CP were more likely to show greater contralesional
HSN. Unlike a previous study that also investigated a correlation between the degree of CP and intensity of HSN (12), our study showed that HSN can represent the remnant vestibular reservoir in the affected ear during the follow-up of unilateral MD. Of interest, HSN occurred in the opposite direction of SN in 13.3% of occasions during the irritative phase and in 11.1% during the paretic phase. Development of HSN in the opposite direction of SN has previously been reported in lateral medullary (LMI) and cerebellar infarctions (21,24,25) and has been considered one of the central patterns of HSN. In LMI and cerebellar infarctions, the HSN beating to the lesion side has been explained by ipsilesional disinhibition of the velocity storage mechanism by damaging the fibers from the nodulus and ventral uvula to the vestibular nuclei (21). However, given the occasional dissociations in the direction of SN and HSN during the acute phases of unilateral MD, the clinical implication of HSN in the opposite direction of SN should be interpreted with caution in the context of accompanying symptoms and signs. Although the horizontal direction of HSN did not change over time in most patients with LMI (10/11, 90.9%) (21), the HSN in the opposite direction of SN showed a resolution or direction reversal over time in most of our patients with unilateral MD. These findings also indicate that the static vestibular imbalance is not always in accordance with the dynamic one during the acute phases of MD. Vibration-induced Nystagmus Vibratory stimuli applied either to the mastoids, forehead, or even to the neck muscles may induce nystagmus in patients with peripheral (12,26,27) or central vestibulopathies (21). Because of simultaneous stimulation of the vestibular receptors on both sides during the vibratory stimuli, VIN is considered to represent asymmetrical peripheral vestibular input in peripheral vestibular disorders. In our patients, VIN beat mostly toward the healthy ear side when observed, irrespective of the phases when the evaluation was performed. These findings are consistent with those reported in the previous studies (12,13,28). In contrast to head-shaking, vibration is known to induce nystagmus by stimulating both vestibular organs directly (28). Given the predominant contralesional VIN irrespective of the phases evaluated, relative hypofunction of the ipsilesional hair cells involved in the generation of VIN appears to be maintained throughout the phases of MD. In a previous study performed during the interictal periods of MD by the authors, the direction of VIN correlated well with the severity of CP, and contralesional VIN was more likely to occur in patients with more severe CP (12). This correlation was also replicated in the current study and suggests that VIN is more related to the excitability of Type II hair cells that are rather selectively destroyed in MD (12). However, the correlation between the direction of ictal VIN and severity of interictal CP was insignificant. We assume that factors other than interictal CP may be involved in determining the direction of VIN during the acute phases of MD.
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NYSTAGMUS DURING ATTACKS OF ME´NIE`RE_S DISEASE Of interest, the proportion of contralesional VIN increased during the irritative phase. Because the static vestibular inputs from the affected ear would be larger than those from the healthy ear during the irritative phases, the underlying vestibular imbalance may have been reversed during the vibratory stimuli, possibly as a result of stimulation of the intact Type II hair cells in the healthy ear. Directional Dissociation Between HSN and VIN In our study, directional dissociation of HSN and VIN was observed in 32 of the total 213 occasions (15.0%) and was especially more common during the irritative phases (21/55, 38.2%). This directional dissociation has also been described in MD (13,28) as well as in other disorders including LMI (21), vestibular neuritis (29), and RamsayHunt syndrome (29). The proportion of this dissociation observed in this study seems to be somewhat lower than that reported previously in MD (18.1Y65.0%) (13,28). This discrepancy may be explained by different stimulation methods and positive criteria, dissimilar proportion of the phases when the evaluation was performed, or different proportion of disease stages. The directional dissociation between VIN and HSN may reflect different mechanisms involved in generation of each nystagmus. Although HSN is generally believed to represent the vestibular imbalance accumulated in the central velocity storage system, the VIN seems to represent an asymmetry in the excitability of the peripheral vestibular apparatus (30). Given the instant onset and offset nature of VIN, the velocity storage system seems to contribute little, if any, to generation of VIN. Furthermore, one labyrinth is stimulated whereas the other is inhibited during horizontal head-shaking (push-and-pull effect), but vibration stimulates both labyrinth simultaneously (28). The different frequency of stimuli during head-shaking and vibration may be another explanation for this discrepancy. Patients with MD show a selective loss of Type II hair cells in the vestibular end organs (31). Indeed, patients with MD frequently exhibit normal gain of the VOR during head impulse tests in the presence of severe CP (11). This indicates that the remaining hair cells respond differently according to the stimulation frequency in MD. The different vestibular compensation according to stimulation frequency may also contribute to this directional dissociation (32). In our study, the prevalence of this directional dissociation differed from phase to phase, most common during the irritative phase. This was mostly caused by the increased proportion of ipsilesional HSN during the irritative phase. The increased prevalence of ipsilesional HSN seems plausible given that HSN is initiated by asymmetric peripheral vestibular inputs in peripheral vestibular disorders. The pattern of directional dissociation between HSN and VIN observed in our patients with MD is dissimilar to that reported in LMI (21) in which the VIN beat in the direction of SN whereas the HSN beat almost always toward the lesion side. In LMI, the consistent ipsilesional
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HSN was ascribed to asymmetric disinhibition of the velocity storage system (21).
CONCLUSION The characteristic findings of HSN and VIN during each phase of MD would aid in defining the acute phases of MD and understanding the underlying pathomechanisms.
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