The Laryngoscope C 2015 The American Laryngological, V
Rhinological and Otological Society, Inc.
The Map of Dizziness in Vestibular Schwannoma Angel Batuecas-Caletrio, MD, PhD; Santiago Santa Cruz-Ruiz, MD, PhD; ~ oz-Herrera, MD; Nicolas Perez-Fernandez, MD, PhD Angel Mun Introduction: Dizziness is a frequent complaint in patients with vestibular schwannoma (VS). An abnormal vestibuloocular reflex (VOR) can explain this dizziness in patients with VS. The video Head impulse test (vHIT) offers a chance to describe specifically the VOR findings in such patients. Study Design: Retrospective cases series study in a tertiary referral hospital. Methods: Fifty consecutive patients with VS were classified in accordance with the morphology of the VOR; gain, covert saccade, and overt saccade were analyzed both in the affected side and in the healthy side. For all patients, caloric tests were performed. All patients were tested before surgery. Results: Caloric response was normal in 31 of 50 patients. The video Head impulse test was abnormal in 45 of 50 patients. For the affected side, low horizontal VOR gain was found in 27 of 50 patients, covert saccade was observed in 37 of 50, and overt saccade was observed in 26 of 50. In the healthy side, vHIT was abnormal in 29 of 50 patients, with a low gain in four of 50, covert saccade in seven of 50, and overt saccade in 23 of 50. In VS, gain for the affected side is not associated with caloric response, but gain for the affected side is associated with gain in the healthy side. Covert and overt saccade for the affected side is associated with gain for the affected side. In the healthy side, overt saccade is associated with low gain for the affected side. Conclusions: Video head impulse test improves the vestibular testing before surgery in patients with VS and should be included in the usual clinical tests for these patients. Key Words: Vestibulo-ocular reflex, vestibular schwannoma, video Head Impulse test, vestibular compensation. Level of Evidence: 4. Laryngoscope, 125:2784–2789, 2015
INTRODUCTION In patients with vestibular schwannoma (VS), unilateral progressive hearing loss and tinnitus are the most frequent symptoms, and dizziness shows a marked variability in terms of clinical presentation. The former symptoms have a strong psychological impact, whereas dizziness is most relevant to functional impairment.1,2 Vestibular schwannoma is a slowly and irregularly growing benign tumor.3 While growing, vestibular function diminishes, which is clinically associated with postural instability and more easily identified in dynamic rather than static posturography.4 The slowly progressive reduction of vestibular function allows the gradual implementation of central adaptive mechanisms (vestibular compensation), which minimize VS-related symptoms, such as a perceptual syndrome with vertigo or
From the Department of Otorhinolaryngology, Otoneurology Unit, University Hospital of Salamanca, University of Salamanca (A.B-C., S.S-R., A.M-H.), Salamanca; and the Cl ınica Universidad de Navarra, University Hospital and Medical School, University of Navarra (N.P-F.), Pamplona, Spain Editor’s Note: This Manuscript was accepted for publication May 4, 2015. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Dr. Angel Batuecas Caletrıo, Department of Otorhinolaryngology, Pso S. Vicente 58-182, 37007 Salamanca, Spain. E-mail: [email protected] DOI: 10.1002/lary.25402
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dizziness, and clinical signs, such as body and limb deviation or nystagmus as seen in acute vestibular deficit.5,6 Vestibular tests do not have a high sensitivity for detecting VS, and results are usually nonspecific.7 However, preoperative vestibular function (as measured by the caloric test) is of great interest and its clinical relevance has been well established; patients with a poor vestibular function before surgery recover earlier and to a greater extent than patients with a normal preoperative vestibular function.8 Indeed, poor vestibular function is associated with tumor size, mainly in large tumors. One of the most important bedside clinical tests for studying vestibular function is the head-impulse test.9 In normal subjects, when unpredictable head impulses are performed rightward or leftward, the eye drifts in the direction contrary to that imposed to the head and at the same velocity; the latency of this reflex is less than 10 ms and the net effect is that the gaze is kept stable on the fixation target. When the head movement is performed to the side with a vestibular deficit, the reflexive eye movement occurs with a lower speed than needed, and the eye deviates partially in the same direction of the head, leading to retinal slip and visual blurring. In this situation, the patient needs to produce a quick eye movement or refixation saccade (RS), which adds to the initial reflexive eye movement to keep gaze on the original target. The video head-impulse test (vHIT) is a new tool that simultaneously records head and eye velocities Batuecas-Caletrio et al.: Dizziness and Vestibular Schwannoma
during and after the head impulse. It has been validated against the scleral search coil method for the measurement of the vestibulo-ocular reflex (VOR) and has shown an almost complete correspondence of results: the velocity profile recorded was identical and the replicability between tests with each system was greater than 0.9.10 For head movements in the yaw axis, side-to-side, a normative study has been recently published for the velocity results but also for the RS.11 In relation to other tests of vestibular function, and in particular of the horizontal semicircular canal, we must stress that the caloric test and the vHIT measure vestibular deficit in very different ways due not only to the nature of the stimulus in use but also to the type of response they analyze. The caloric test uses a nonphysiological stimulation that closely matches a very lowfrequency sinusoidal rotation, whereas the vHIT uses a fast angular high-frequency stimulation. In the former, the response is a burst of nystagmus that continues for almost 2 minutes; whereas in the later, the response is purely the VOR that, as mentioned before, occurs at the same velocity and short latency, fading as the head stops. This explains the well known differences in results when the same patient is under evaluation.12 In patients with an acute or stable vestibular deficit RS are thought to substitute the delayed and reduced VOR during head impulses toward the damaged side.13 They have been classified as covert14 when they occur while the head is still moving15 and overt when they occur once the head movement is finished. Interestingly, the former usually go undetected during clinical exam, and specific head movement paradigms or special technical solutions (like the vHIT) are needed to reveal them. The aim of this study was to evaluate the vHIT in patients with VS and to analyze the occurrence of refixation saccades.
MATERIALS AND METHODS Patients Fifty patients with unilateral VS participated in this study. This report deals with the vestibular testing results obtained before any modality of treatment has been performed: some patients are in a wait-and-see state and others have not been surgically treated yet. Patients with a history of fluctuating hearing loss or tinnitus, vestibular neuritis, or positional vertigo affecting the oncologically unaffected ear were excluded.
Assessment The VOR was evaluated with the head-impulse test. In this test, the physician stands behind the patient and holds the patient’s head firmly with both hands. The patient is asked to keep looking at a stationary object on the wall that is at a distance of 1 m. The head is quickly and unpredictably turned through 10 to 20 degrees in the horizontal plane to the left or right, which permits testing of the corresponding horizontal semicircular canal. In order to register and measure head and eye velocity during the head impulse, we have used a vHIT system (GN Otometrics, Taastrup, Denmark). The patient wears a pair of lightweight tight-fitting goggles on which is mounted a small video camera and a half-silvered mirror that reflects the image of the patient’s right eye into the camera. The eye is illuminated by a low-level
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Fig. 1. vHIT in a normal subject of one impulse. In the y-axis, head velocity (black) and eye velocity (gray) along the time (x-axis) are almost similar.
infrared light-emitting diode. A small sensor on the goggles measures the head movement. The whole goggle system weighs about 60 g and is secured tightly to the head to minimize goggle slippage. Calibration is performed, and the procedure of vestibuloocular testing is initiated. The head velocity is measured by the sensor in the goggles, and the image of the eye is captured by the high-speed camera (250 Hz) and processed to yield eye velocity. At the end of each head turn, the head-velocity stimulus and eyevelocity response are displayed simultaneously on the screen (Fig. 1) so the clinician can see how good (a close correlation between both curves) the stimulus and response were, providing a quick way to maximize the quality of the head impulse. In normal conditions (healthy patients), the physician should observe that the patient is able to maintain the eyes fixed on the stationary target during the high-speed head rotation. When unilateral vestibular weakness exists, the eyes drift in the same direction as the head, and then compensatory refixation saccades are used to reset the visual fixation on the target. In a full test, 20 impulses are delivered randomly in each direction. At the end of the full test, all of the head velocity stimuli and eye velocity responses are displayed. In order to evaluate the results, two main parameters were taken into consideration, beginning with absolute mean VOR gain. The gain of the VOR was obtained after each head impulse and calculated as the ratio of eye velocity to head velocity; the procedure in our system measures a ratio of the area under the curves of head velocity and eye velocity. The mean of the different impulses to each direction will be given but as gain referenced to the affected (mean VOR gain for ipsilesional) or nonaffected (contralesional) side. A normal gain is defined when 0.80 and abnormal when < 0.80. A relative value for gain was calculated as the amount of gain asymmetry according to the formula16
Gas5½12ðlower gain=higher gainÞ 100ð%Þ: The second parameter considered was the appearance and eye velocity of saccades after head impulses; saccades were recorded as present or “yes” and absent or “no.” From the XML (eXtensible Markup Language) file of each patient, data regarding the velocity of saccades was obtained and analyzed. For each patient, results from the affected and unaffected ears were registered as covert and overt saccades (Fig. 2). In all the patients, the bithermal alternate caloric test was performed according to Fitzgerald and Hallpike bithermal
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Fig. 2. Video Head impulse test in a left vestibular schwannoma patient. Gain of each impulse toward left healthy side (A) and right affected side (B) is represented. In the left healthy side (C), overt saccades can be observed (D). In the right affected side (E), gain is low (G) and covert (H) and overt (I) saccades are clearly represented. VOR 5 vestibulo-ocular reflex. [Color figure can be viewed in the online issue, which is available at www.laryngoscope.com.] caloric test; the eye movements were recorded by means of a video-based system (Ulmer VNG, v. 1.4, SYNAPSIS, Marseille, France). The maximum slow-phase velocity of the nystagmus was calculated after each irrigation. The total response from each ear was calculated, and caloric weakness and directional preponderance were determined according to Jongkees’ formula. Following radiological evaluation, patients were classified according to Koos:17 grade I when the tumor is in the internal auditory canal (IAC), grade II when the tumor is in the pontocerebellar angle and < 2 cm, grade III when the tumor is in the IAC and 2 cm to 4 cm, and grade IV if the tumor is in the IAC and > 4 cm.
Statistics All data were stored and analyzed in an SPSS file version 19.0 (IBM Corp., Armonk, NY). All tests were two-tailed, and P values < 0.05 were considered significant. According to the gain obtained in the vHIT in the affected side, patients were classified into two groups: group A were patients whose mean VOR gain was normal ( 0.8), and group B were patients whose mean VOR gain was abnormal (< 0.8). Comparison between groups was assessed using the v 2 test for testing independence of proportions regarding string variables, and Students t test was used to compare means of quantitative data.
the affected side and 0.91 6 0.14 for the nonaffected side; the difference was significant (P 5 0.024); and mean gain asymmetry was 24% (range 0%–66%). According to mean VOR gain, 23 patients were classified into group A (normal gain, 0.8) and 27 patients were classified into group B (abnormal gain, < 0.8). Gain in the nonaffected side was found to be significantly lower in B-group patients than in A-group (P < 0.03). According to tumor size, 20 patients were classified as grade I, 16 as grade II, nine as grade III, and five as grade IV (Table I). Canal paresis in the caloric test and gain asymmetry in the vHIT are both associated with the size of the tumor (P 5 0.018 and P 5 0.009, respectively); mean canal paresis and gain asymmetry are associated only with big tumors: grade III (P 5 0.04) and grade IV (P 5 0.035). For head impulses to the affected side, only in five patients were results normal. Gain was > 0.8 and there were no refixation saccades. In the rest of the patients
TABLE I. Spontaneus Nystagmus, Canal Paresis, and vHIT Asymmetry.
RESULTS In this study, there were 21 men and 29 women with a mean age of 52 6 13 years. In 28 patients, the VS was located in the left side and in 22 in the right side. Mean pure tone audiometry (PTA) was 41 6 31 dBHL in the affected ear. The caloric test was normal in 19 patients and abnormal in 31 (62%); mean canal paresis was 46% 6 32%. Mean gain of VOR was 0.74 6 0.23 for Laryngoscope 125: December 2015
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N
Spontaneous Nystagmus (yes/no)
Canal Paresis (caloric test) %
Asymetry (vHIT) %
Grade I Grade II
20 16
4/16 5/11
42 6 33 44 6 26
16 6 14 25 6 21
Grade III
9
5/4
52 6 35
32 6 19
Grade IV
5
4/5
64 6 34
39 6 29
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(as it is in our study), leftward directed impulses tend to be provide lower gain. Because of this, in a previous work using a similar vHIT system, mean leftward head impulses gain was found to be lower than rightward but without clinical significance.11 The ratio of tumor location (right/left) is almost similar; thus, this effect was not found to be of relevance. Lastly, a recent work has shown that the modality of initiating the head impulse toward the affected side (from unaffected side to headcenter or from head-center toward affected side) has a predictable effect on the latency of covert and overt saccades, and that overt saccades are also more frequent on the first modality of stimulation. However, it did not find differences in the occurrence of covert saccades based on the direction of the head impulse.20 In order to rule out this possible bias in all patients, the test was performed from head-center to affected or unaffected side. Fig. 3. Overt saccades in the healthy side are related to a low gain in the affected side.
The Affected Side (45), the abnormal results were the following: low gain in 27 patients, covert saccades in 37, and overt saccades in 25 (both covert and overt saccades were found in 19). Mean velocity of refixation saccades was 199 6 398/s for covert and 160 6 508/s for overt, and the difference was significant (P 5 0.039). For head impulses directed to the unaffected side, the results were normal in 21 patients. Gain was > 0.8 and there were no refixation saccades. Abnormal results were: low gain in four patients, presence of covert saccades in seven and of overt saccades in 23. Mean velocity of covert saccades was 121 6 168/s and of overt saccades 79 6 138/s, and the differences were not significant. In the unaffected side, RS were not found to be associated with the gain for that side (P 5 0.732) but with gain for the affected side (P 5 0.017) (Fig. 3). They were more frequent in B-group patients (27/27) than in A-group patients (19/23).
DISCUSSION In our work, we were interested in the detailed findings obtained after examination of the VOR elicited with fast and unpredictable head impulses to the side where the VS is located (affected side) and to the contrary (unaffected side). Three remarks are needed before going into details of the work. Firstly, we have measured the function conveyed by one of the subdivisions of the vestibular nerve because the horizontal canal afferents are part of the superior vestibular nerve. Both the vHIT and the caloric test mainly stimulate the horizontal semicircular canal receptor by provoking a current of endolymph; the stimulation provokes some minor response in the vertical canals because of their particular orientation18 but with limited effect on the analyzed response. Secondly, the side of the affected ear could account for subtle differences in our study because the gain of the VOR is somewhat lower when analyzed in the abducting eye than when analyzed in the adducting eye.19 As such, when the right eye is under evaluation after head impulses Laryngoscope 125: December 2015
Previous work has shown that the size of the tumor correlates with the results in tests that evaluate the vestibular deficit conveyed in the different branches of the vestibular nerve as from the horizontal semicircular canal receptors in the caloric test21 and from the utricular and saccular maculae in the Vestibular Evoked Myogenic Potential evaluation.22 We have shown here that the degree of vestibular deficit correlates with tumor size both for the caloric test and vHIT. Our results are very much similar to precedent work23 because mean canal paresis is similar, but mean gain asymmetry of the VOR is higher in our case. This could be related to differences in tumor size between patients in both studies, as in our case 72% of the patients were grade I or II, and in theirs this amount was 57%. We have also to take into account that the formula used to calculate the relative right–left asymmetry in the VOR gain is different in both studies. The second variable that was used to evaluate the response was RS, which occurs because the eye movement is less than expected in accordance with the head impulse. As a result, a position error occurs, and a fast movement or catch-up saccade is recruited to refixate the eye on target. When head impulses were delivered to the affected side, RS was the norm in accordance with findings in patients with low-gain VOR. The use of RS to classify the test result provides a higher capability for the vHIT compared to the caloric test because in the former the number of abnormal tests was 45 of 50 patients.
The Unaffected Side The results obtained after testing the affected side are easily understandable in terms of a reduced response after stimulation of the receptor due to damage in the vestibular nerve fibers. However, the results obtained after stimulation of the nonaffected side deserve some remarks. First, we found an abnormal VOR in four patients, which in those patients may reflect the existence of subclinical or unnoticed vestibular damage, Batuecas-Caletrio et al.: Dizziness and Vestibular Schwannoma
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although exclusion criteria were set to minimize that event. Nevertheless, it may represent sequelae of acute otitis media in infancy24 as the result of a mild temporal bone concussion25,26 or be a progressive vestibulopathy. Interestingly, in these patients this finding was not correlated with a caloric bilateral weakness. This stresses the importance of examining these patients with both methods because the need to implement a program of vestibular rehabilitation will be highlighted with some particularities in those with a bilateral vestibular deficit according to the vHIT.27 Gain for the unaffected side was found to be significantly lower in patients with an abnormal gain in the affected side (group B). Although this has been reported in patients with acute unilateral peripheral vestibulopathy of different etiologies, it is interesting to note that this finding occurs even in a homogeneous group, showing the need of using not only absolute values but also the amount of gain asymmetry, as others have also shown.28 This reduced gain for the unaffected side is explained by the relationship between both vestibular nuclei through commissural connections.29 They suggested that some of type-II neurons are intercalated inhibitory neurons activated by contralateral horizontal canal stimulation through commissural fibers inhibiting homolateral type-I neurons. As such, type-I secondary vestibular neurons are not only excited by activation of the same side horizontal canal but are also disinhibited by disfacilitation from the contralateral horizontal canal. This was demonstrated with scleral search coils some time later.30 Gain in a healthy person results from the combination of excitation from the excited semicircular canal and disinhibition originating from the contralateral horizontal canal. In VS, unilateral vestibular loss is common. We have shown that gain for the affected side is usually low, and this low gain can contribute to not produce a disinhibition in the turns of the head toward the healthy side. Consequently, when gain for the affected side is low or very low, we can observe a low gain in the healthy side. For this reason, the frequency of RS after head impulses to the nonaffected side was not an unexpected finding. We have seen that the velocity of both the covert (while the head is still moving) and overt (after the head impulse ends) RS is somewhat lower after head impulses to the nonaffected than to the affected side. Furthermore, RS after impulses to the nonaffected side are correlated with gain after impulses to the affected side. We consider that the appearance of overt saccades in the healthy side in patients with a progressive loss of vestibular function in the affected side could be explained by the absence of disinhibition from the affected side in the vestibular system, and that saccades are not a sign of vestibular dysfunction in the healthy side.31
CONCLUSION In conclusion, we have shown that with this modality of evaluation the detection of the vestibular deficit and its consequences in the VOR are superior to the Laryngoscope 125: December 2015
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conventional caloric test. Taking into account the low level of discomfort because neither vertigo nor nausea is elicited, contrary to what occurs with the caloric test, this test should be the first line when a vestibulopathy is suspected. Unfortunately, it does not provide a pathognomonic sign, but the findings will prompt more indepth investigations. In particular, we want to stress the utility of analyzing information from the unaffected side (i.e., a low gain associated with RS). It will also be interesting to know whether this is of interest in the clinical follow-up of these patients should they undergo surgical treatment or remain in a wait-and-see program.
BIBLIOGRAPHY 1. Myrseth E, Moller P, Wentzel-Larsen T, Goplen F, Lund-Johansen M. Untreated vestibular schwannomas: vertigo is a powerful predictor for health-related quality of life. Neurosurgery 2006;59:67–76. 2. Brooker JE, Fletcher JM, Dally MJ, et al. Factors associated with symptom-specific psychological and functional impact among acoustic neuroma patients. J Laryngol Otol 2014;128(suppl 2):S16–S26. doi: 10.1017/S0022215113003216. Epub 2013. 3. Nikolopoulos TP, Fortnum H, O’Donoghue G, Baguley D. Acoustic neuroma growth: a systematic review of the evidence. Otol Neurotol 2010; 31:478–485. 4. Andersen JF, Nilsen KS, Vassbotn FS, et al. Predictors of vertigo in patients with untreated vestibular schwannoma. Otol Neurotol 2015;36: 647–652. 5. Curthoys IS. Vestibular compensation and substitution. Curr Opin Neurol 2000;13:27–30. 6. Parietti-Winkler C, Gauchard GC, Simon C, Perrin PP. Visual sensorial preference delays balance control compensation after vestibular schwannoma surgery. Neuroscience 2011;172:285–292. 7. Huang CH, Wang SJ, Young YH. Correlation between caloric and ocular vestibular evoked myogenic potential test results. Acta Otolaryngologica 2011;131: 123–125. 8. Batuecas-Caletrio A, Santacruz-Ruiz S, Munoz-Herrera A, Sousa P, Otero A, Perez-Fernandez N. Vestibular compensation after vestibular schwannoma surgery: normalization of the subjective visual vertical and disability. Acta Otolaryngol 2013;133:475–480. 9. Halmagyi GM, Curthoys IS. A clinical sign of canal paresis. Arch Neurol 1988;45:37–39. 10. MacDougall HG, Weber KP, McGarvie LA, Halmagyi GM, Curthoys IS. The video head impulse test: diagnostic accuracy in peripheral vestibulopathy. Neurology 2009;73:1134–1141. 11. Matino-Soler E, Esteller-More E, Martin-Sanchez JC, Martinez-Sanchez JM, Perez-Fernandez N. Normative data on angular vestibulo-ocular responses in the yaw axis measured using the video head impulse test. Otol Neurotol 2015;36:466–471. 12. Blodow A, Helbig R, Wichmann N, Wenzel A, Walther LE, Bloching MB. Video head impulse test or caloric irrigation?. Contemporary diagnostic tests for vestibular schwannoma. HNO 2013;61:781–785. 13. Blodow A, Pannasch S, Walther LE. Detection of isolated covert saccades with the video head impulse test in peripheral vestibular disorders. Auris Nasus Larynx 2013;40:348–351. 14. Weber KP, Aw ST, Todd MJ, McGarvie LA, Curthoys IS, Halmagyi GM. Head impulse test in unilateral vestibular loss: vestibulo-ocular reflex and catch-up saccades. Neurology 2008;70:454–463. 15. Tjernstrom F, Nystrom A, Magnusson M. How to uncover the covert saccade during the head impulse test. Otol Neurotol 2012;33:1583–1585. 16. Newman-Toker DE, Saber Tehrani AS, Mantokoudis G, et al. Quantitative video-oculography to help diagnose stroke in acute vertigo and dizziness: toward an ECG for the eyes. Stroke 2013;1158–1161. 17. Koos WT, Spetzler RF, Bock FW. Microsurgery of cerebellopontine angle tumors. In: Koos WT, Bock FW, Spetzler RF, et al, eds. Clinical Microneurosurgery. Sttutgart, Germany and Acton, MA: Georg Thieme; 1976: 91–112. 18. Della Santina CC, Potyagaylo V, Migliaccio AA, Minor LB, Carey JP. Orientation of human semicircular canals measured by three-dimensional multiplanar CT reconstruction. J Assoc Res Otolaryngol 2005;6:191–206. 19. Weber KP, Aw ST, Todd MJ, et al. Inter-ocular differences of the horizontal vestibulo-ocular reflex during impulsive testing. Prog Brain Res 2008; 171:195–198. 20. Lee SH, Newman-Toker DE, Zee DS, Schubert MC. Compensatory saccade differences between outward versus inward head impulses in chronic unilateral vestibular hypofunction. J Clin Neurosci 2014;21:1744–1749. 21. Tringali S, Charpiot A, Ould MB, Dubreuil C, Ferber-Viart C. Characteristics of 629 vestibular schwannomas according to preoperative caloric responses. Otol Neurotol 2010;31:467–472. 22. Lin KL, Chen CM, Wang SJ, Young YH. Correlating vestibular schwannoma size with vestibular-evoked myogenic potential results. Ear Hear 2014;35:571–576.
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23. Blodow A, Blodow J, Bloching MB, Helbig R, Walther LE. Horizontal VOR function shows frequency dynamics in vestibular schwannoma. Eur Arch Otorhinolaryngol 2014. Epub ahead of print. 24. Casselbrant ML, Villardo RJ, Mandel EM. Vestibular and stabilometric findings in whiplash injury and minor head trauma. Balance and otitis media with effusion. Int J Audiol 2008;47:584–589. 25. Nacci A, Ferrazzi M, Berrettini S, et al. Vestibular and stabilometric findings in whiplash injury and minor head trauma. Acta Otorhinolaryngol Ital 2011;31:378–389. 26. Scherer MR, Shelhamer MJ, Schubert MC. Characterizing high-velocity angular vestibulo-ocular reflex function in service members post-blast exposure. Exp Brain Res 2011;208:399–410. 27. Prepageran N, Kisilevsky V, Tomlinson D, Ranalli P, Rutka J. Symptomatic high frequency/acceleration vestibular loss: consideration of a new
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clinical syndrome of vestibular dysfunction. Acta Otolaryngol 2005;125: 48–54. Mantokoudis G, Saber Tehrani AS, Wozniak A, et al. VOR gain by head impulse video-oculography differentiates acute vestibular neuritis from stroke. Otol Neurotol 2015;36:457–465. Shimazu H, Precht W. Inhibition of central vestibular neurons from the contralateral labyrinth and its mediating pathway. J Neurophysiol 1966; 29:467–492. Halmagyi GM, Curthoys IS, Cremer PD, et al. The human horizontal vestibule-ocular reflex in response to high acceleration stimulation before and after unilateral vestibular neurectomy. Exp Brain Res 1990;81: 479–490. Lehnen N, Glasauer S, Jahn K, Weber KP. Head impulses in complete bilateral vestibular loss: catch-up saccades require visual input. Neurology 2013;81:688–690. doi: 10.1212/WNL.0b013e3182a08d36.
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The Map of Dizziness in Vestibular Schwannoma Angel Batuecas-Caletrio, MD, PhD; Santiago Santa Cruz-Ruiz, MD, PhD; ~ oz-Herrera, MD; Nicolas Perez-Fernandez, MD, PhD Angel Mun Introduction: Dizziness is a frequent complaint in patients with vestibular schwannoma (VS). An abnormal vestibuloocular reflex (VOR) can explain this dizziness in patients with VS. The video Head impulse test (vHIT) offers a chance to describe specifically the VOR findings in such patients. Study Design: Retrospective cases series study in a tertiary referral hospital. Methods: Fifty consecutive patients with VS were classified in accordance with the morphology of the VOR; gain, covert saccade, and overt saccade were analyzed both in the affected side and in the healthy side. For all patients, caloric tests were performed. All patients were tested before surgery. Results: Caloric response was normal in 31 of 50 patients. The video Head impulse test was abnormal in 45 of 50 patients. For the affected side, low horizontal VOR gain was found in 27 of 50 patients, covert saccade was observed in 37 of 50, and overt saccade was observed in 26 of 50. In the healthy side, vHIT was abnormal in 29 of 50 patients, with a low gain in four of 50, covert saccade in seven of 50, and overt saccade in 23 of 50. In VS, gain for the affected side is not associated with caloric response, but gain for the affected side is associated with gain in the healthy side. Covert and overt saccade for the affected side is associated with gain for the affected side. In the healthy side, overt saccade is associated with low gain for the affected side. Conclusions: Video head impulse test improves the vestibular testing before surgery in patients with VS and should be included in the usual clinical tests for these patients. Key Words: Vestibulo-ocular reflex, vestibular schwannoma, video Head Impulse test, vestibular compensation. Level of Evidence: 4. Laryngoscope, 125:2784–2789, 2015
INTRODUCTION In patients with vestibular schwannoma (VS), unilateral progressive hearing loss and tinnitus are the most frequent symptoms, and dizziness shows a marked variability in terms of clinical presentation. The former symptoms have a strong psychological impact, whereas dizziness is most relevant to functional impairment.1,2 Vestibular schwannoma is a slowly and irregularly growing benign tumor.3 While growing, vestibular function diminishes, which is clinically associated with postural instability and more easily identified in dynamic rather than static posturography.4 The slowly progressive reduction of vestibular function allows the gradual implementation of central adaptive mechanisms (vestibular compensation), which minimize VS-related symptoms, such as a perceptual syndrome with vertigo or
From the Department of Otorhinolaryngology, Otoneurology Unit, University Hospital of Salamanca, University of Salamanca (A.B-C., S.S-R., A.M-H.), Salamanca; and the Cl ınica Universidad de Navarra, University Hospital and Medical School, University of Navarra (N.P-F.), Pamplona, Spain Editor’s Note: This Manuscript was accepted for publication May 4, 2015. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Dr. Angel Batuecas Caletrıo, Department of Otorhinolaryngology, Pso S. Vicente 58-182, 37007 Salamanca, Spain. E-mail: [email protected] DOI: 10.1002/lary.25402
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dizziness, and clinical signs, such as body and limb deviation or nystagmus as seen in acute vestibular deficit.5,6 Vestibular tests do not have a high sensitivity for detecting VS, and results are usually nonspecific.7 However, preoperative vestibular function (as measured by the caloric test) is of great interest and its clinical relevance has been well established; patients with a poor vestibular function before surgery recover earlier and to a greater extent than patients with a normal preoperative vestibular function.8 Indeed, poor vestibular function is associated with tumor size, mainly in large tumors. One of the most important bedside clinical tests for studying vestibular function is the head-impulse test.9 In normal subjects, when unpredictable head impulses are performed rightward or leftward, the eye drifts in the direction contrary to that imposed to the head and at the same velocity; the latency of this reflex is less than 10 ms and the net effect is that the gaze is kept stable on the fixation target. When the head movement is performed to the side with a vestibular deficit, the reflexive eye movement occurs with a lower speed than needed, and the eye deviates partially in the same direction of the head, leading to retinal slip and visual blurring. In this situation, the patient needs to produce a quick eye movement or refixation saccade (RS), which adds to the initial reflexive eye movement to keep gaze on the original target. The video head-impulse test (vHIT) is a new tool that simultaneously records head and eye velocities Batuecas-Caletrio et al.: Dizziness and Vestibular Schwannoma
during and after the head impulse. It has been validated against the scleral search coil method for the measurement of the vestibulo-ocular reflex (VOR) and has shown an almost complete correspondence of results: the velocity profile recorded was identical and the replicability between tests with each system was greater than 0.9.10 For head movements in the yaw axis, side-to-side, a normative study has been recently published for the velocity results but also for the RS.11 In relation to other tests of vestibular function, and in particular of the horizontal semicircular canal, we must stress that the caloric test and the vHIT measure vestibular deficit in very different ways due not only to the nature of the stimulus in use but also to the type of response they analyze. The caloric test uses a nonphysiological stimulation that closely matches a very lowfrequency sinusoidal rotation, whereas the vHIT uses a fast angular high-frequency stimulation. In the former, the response is a burst of nystagmus that continues for almost 2 minutes; whereas in the later, the response is purely the VOR that, as mentioned before, occurs at the same velocity and short latency, fading as the head stops. This explains the well known differences in results when the same patient is under evaluation.12 In patients with an acute or stable vestibular deficit RS are thought to substitute the delayed and reduced VOR during head impulses toward the damaged side.13 They have been classified as covert14 when they occur while the head is still moving15 and overt when they occur once the head movement is finished. Interestingly, the former usually go undetected during clinical exam, and specific head movement paradigms or special technical solutions (like the vHIT) are needed to reveal them. The aim of this study was to evaluate the vHIT in patients with VS and to analyze the occurrence of refixation saccades.
MATERIALS AND METHODS Patients Fifty patients with unilateral VS participated in this study. This report deals with the vestibular testing results obtained before any modality of treatment has been performed: some patients are in a wait-and-see state and others have not been surgically treated yet. Patients with a history of fluctuating hearing loss or tinnitus, vestibular neuritis, or positional vertigo affecting the oncologically unaffected ear were excluded.
Assessment The VOR was evaluated with the head-impulse test. In this test, the physician stands behind the patient and holds the patient’s head firmly with both hands. The patient is asked to keep looking at a stationary object on the wall that is at a distance of 1 m. The head is quickly and unpredictably turned through 10 to 20 degrees in the horizontal plane to the left or right, which permits testing of the corresponding horizontal semicircular canal. In order to register and measure head and eye velocity during the head impulse, we have used a vHIT system (GN Otometrics, Taastrup, Denmark). The patient wears a pair of lightweight tight-fitting goggles on which is mounted a small video camera and a half-silvered mirror that reflects the image of the patient’s right eye into the camera. The eye is illuminated by a low-level
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Fig. 1. vHIT in a normal subject of one impulse. In the y-axis, head velocity (black) and eye velocity (gray) along the time (x-axis) are almost similar.
infrared light-emitting diode. A small sensor on the goggles measures the head movement. The whole goggle system weighs about 60 g and is secured tightly to the head to minimize goggle slippage. Calibration is performed, and the procedure of vestibuloocular testing is initiated. The head velocity is measured by the sensor in the goggles, and the image of the eye is captured by the high-speed camera (250 Hz) and processed to yield eye velocity. At the end of each head turn, the head-velocity stimulus and eyevelocity response are displayed simultaneously on the screen (Fig. 1) so the clinician can see how good (a close correlation between both curves) the stimulus and response were, providing a quick way to maximize the quality of the head impulse. In normal conditions (healthy patients), the physician should observe that the patient is able to maintain the eyes fixed on the stationary target during the high-speed head rotation. When unilateral vestibular weakness exists, the eyes drift in the same direction as the head, and then compensatory refixation saccades are used to reset the visual fixation on the target. In a full test, 20 impulses are delivered randomly in each direction. At the end of the full test, all of the head velocity stimuli and eye velocity responses are displayed. In order to evaluate the results, two main parameters were taken into consideration, beginning with absolute mean VOR gain. The gain of the VOR was obtained after each head impulse and calculated as the ratio of eye velocity to head velocity; the procedure in our system measures a ratio of the area under the curves of head velocity and eye velocity. The mean of the different impulses to each direction will be given but as gain referenced to the affected (mean VOR gain for ipsilesional) or nonaffected (contralesional) side. A normal gain is defined when 0.80 and abnormal when < 0.80. A relative value for gain was calculated as the amount of gain asymmetry according to the formula16
Gas5½12ðlower gain=higher gainÞ 100ð%Þ: The second parameter considered was the appearance and eye velocity of saccades after head impulses; saccades were recorded as present or “yes” and absent or “no.” From the XML (eXtensible Markup Language) file of each patient, data regarding the velocity of saccades was obtained and analyzed. For each patient, results from the affected and unaffected ears were registered as covert and overt saccades (Fig. 2). In all the patients, the bithermal alternate caloric test was performed according to Fitzgerald and Hallpike bithermal
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Fig. 2. Video Head impulse test in a left vestibular schwannoma patient. Gain of each impulse toward left healthy side (A) and right affected side (B) is represented. In the left healthy side (C), overt saccades can be observed (D). In the right affected side (E), gain is low (G) and covert (H) and overt (I) saccades are clearly represented. VOR 5 vestibulo-ocular reflex. [Color figure can be viewed in the online issue, which is available at www.laryngoscope.com.] caloric test; the eye movements were recorded by means of a video-based system (Ulmer VNG, v. 1.4, SYNAPSIS, Marseille, France). The maximum slow-phase velocity of the nystagmus was calculated after each irrigation. The total response from each ear was calculated, and caloric weakness and directional preponderance were determined according to Jongkees’ formula. Following radiological evaluation, patients were classified according to Koos:17 grade I when the tumor is in the internal auditory canal (IAC), grade II when the tumor is in the pontocerebellar angle and < 2 cm, grade III when the tumor is in the IAC and 2 cm to 4 cm, and grade IV if the tumor is in the IAC and > 4 cm.
Statistics All data were stored and analyzed in an SPSS file version 19.0 (IBM Corp., Armonk, NY). All tests were two-tailed, and P values < 0.05 were considered significant. According to the gain obtained in the vHIT in the affected side, patients were classified into two groups: group A were patients whose mean VOR gain was normal ( 0.8), and group B were patients whose mean VOR gain was abnormal (< 0.8). Comparison between groups was assessed using the v 2 test for testing independence of proportions regarding string variables, and Students t test was used to compare means of quantitative data.
the affected side and 0.91 6 0.14 for the nonaffected side; the difference was significant (P 5 0.024); and mean gain asymmetry was 24% (range 0%–66%). According to mean VOR gain, 23 patients were classified into group A (normal gain, 0.8) and 27 patients were classified into group B (abnormal gain, < 0.8). Gain in the nonaffected side was found to be significantly lower in B-group patients than in A-group (P < 0.03). According to tumor size, 20 patients were classified as grade I, 16 as grade II, nine as grade III, and five as grade IV (Table I). Canal paresis in the caloric test and gain asymmetry in the vHIT are both associated with the size of the tumor (P 5 0.018 and P 5 0.009, respectively); mean canal paresis and gain asymmetry are associated only with big tumors: grade III (P 5 0.04) and grade IV (P 5 0.035). For head impulses to the affected side, only in five patients were results normal. Gain was > 0.8 and there were no refixation saccades. In the rest of the patients
TABLE I. Spontaneus Nystagmus, Canal Paresis, and vHIT Asymmetry.
RESULTS In this study, there were 21 men and 29 women with a mean age of 52 6 13 years. In 28 patients, the VS was located in the left side and in 22 in the right side. Mean pure tone audiometry (PTA) was 41 6 31 dBHL in the affected ear. The caloric test was normal in 19 patients and abnormal in 31 (62%); mean canal paresis was 46% 6 32%. Mean gain of VOR was 0.74 6 0.23 for Laryngoscope 125: December 2015
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N
Spontaneous Nystagmus (yes/no)
Canal Paresis (caloric test) %
Asymetry (vHIT) %
Grade I Grade II
20 16
4/16 5/11
42 6 33 44 6 26
16 6 14 25 6 21
Grade III
9
5/4
52 6 35
32 6 19
Grade IV
5
4/5
64 6 34
39 6 29
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(as it is in our study), leftward directed impulses tend to be provide lower gain. Because of this, in a previous work using a similar vHIT system, mean leftward head impulses gain was found to be lower than rightward but without clinical significance.11 The ratio of tumor location (right/left) is almost similar; thus, this effect was not found to be of relevance. Lastly, a recent work has shown that the modality of initiating the head impulse toward the affected side (from unaffected side to headcenter or from head-center toward affected side) has a predictable effect on the latency of covert and overt saccades, and that overt saccades are also more frequent on the first modality of stimulation. However, it did not find differences in the occurrence of covert saccades based on the direction of the head impulse.20 In order to rule out this possible bias in all patients, the test was performed from head-center to affected or unaffected side. Fig. 3. Overt saccades in the healthy side are related to a low gain in the affected side.
The Affected Side (45), the abnormal results were the following: low gain in 27 patients, covert saccades in 37, and overt saccades in 25 (both covert and overt saccades were found in 19). Mean velocity of refixation saccades was 199 6 398/s for covert and 160 6 508/s for overt, and the difference was significant (P 5 0.039). For head impulses directed to the unaffected side, the results were normal in 21 patients. Gain was > 0.8 and there were no refixation saccades. Abnormal results were: low gain in four patients, presence of covert saccades in seven and of overt saccades in 23. Mean velocity of covert saccades was 121 6 168/s and of overt saccades 79 6 138/s, and the differences were not significant. In the unaffected side, RS were not found to be associated with the gain for that side (P 5 0.732) but with gain for the affected side (P 5 0.017) (Fig. 3). They were more frequent in B-group patients (27/27) than in A-group patients (19/23).
DISCUSSION In our work, we were interested in the detailed findings obtained after examination of the VOR elicited with fast and unpredictable head impulses to the side where the VS is located (affected side) and to the contrary (unaffected side). Three remarks are needed before going into details of the work. Firstly, we have measured the function conveyed by one of the subdivisions of the vestibular nerve because the horizontal canal afferents are part of the superior vestibular nerve. Both the vHIT and the caloric test mainly stimulate the horizontal semicircular canal receptor by provoking a current of endolymph; the stimulation provokes some minor response in the vertical canals because of their particular orientation18 but with limited effect on the analyzed response. Secondly, the side of the affected ear could account for subtle differences in our study because the gain of the VOR is somewhat lower when analyzed in the abducting eye than when analyzed in the adducting eye.19 As such, when the right eye is under evaluation after head impulses Laryngoscope 125: December 2015
Previous work has shown that the size of the tumor correlates with the results in tests that evaluate the vestibular deficit conveyed in the different branches of the vestibular nerve as from the horizontal semicircular canal receptors in the caloric test21 and from the utricular and saccular maculae in the Vestibular Evoked Myogenic Potential evaluation.22 We have shown here that the degree of vestibular deficit correlates with tumor size both for the caloric test and vHIT. Our results are very much similar to precedent work23 because mean canal paresis is similar, but mean gain asymmetry of the VOR is higher in our case. This could be related to differences in tumor size between patients in both studies, as in our case 72% of the patients were grade I or II, and in theirs this amount was 57%. We have also to take into account that the formula used to calculate the relative right–left asymmetry in the VOR gain is different in both studies. The second variable that was used to evaluate the response was RS, which occurs because the eye movement is less than expected in accordance with the head impulse. As a result, a position error occurs, and a fast movement or catch-up saccade is recruited to refixate the eye on target. When head impulses were delivered to the affected side, RS was the norm in accordance with findings in patients with low-gain VOR. The use of RS to classify the test result provides a higher capability for the vHIT compared to the caloric test because in the former the number of abnormal tests was 45 of 50 patients.
The Unaffected Side The results obtained after testing the affected side are easily understandable in terms of a reduced response after stimulation of the receptor due to damage in the vestibular nerve fibers. However, the results obtained after stimulation of the nonaffected side deserve some remarks. First, we found an abnormal VOR in four patients, which in those patients may reflect the existence of subclinical or unnoticed vestibular damage, Batuecas-Caletrio et al.: Dizziness and Vestibular Schwannoma
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although exclusion criteria were set to minimize that event. Nevertheless, it may represent sequelae of acute otitis media in infancy24 as the result of a mild temporal bone concussion25,26 or be a progressive vestibulopathy. Interestingly, in these patients this finding was not correlated with a caloric bilateral weakness. This stresses the importance of examining these patients with both methods because the need to implement a program of vestibular rehabilitation will be highlighted with some particularities in those with a bilateral vestibular deficit according to the vHIT.27 Gain for the unaffected side was found to be significantly lower in patients with an abnormal gain in the affected side (group B). Although this has been reported in patients with acute unilateral peripheral vestibulopathy of different etiologies, it is interesting to note that this finding occurs even in a homogeneous group, showing the need of using not only absolute values but also the amount of gain asymmetry, as others have also shown.28 This reduced gain for the unaffected side is explained by the relationship between both vestibular nuclei through commissural connections.29 They suggested that some of type-II neurons are intercalated inhibitory neurons activated by contralateral horizontal canal stimulation through commissural fibers inhibiting homolateral type-I neurons. As such, type-I secondary vestibular neurons are not only excited by activation of the same side horizontal canal but are also disinhibited by disfacilitation from the contralateral horizontal canal. This was demonstrated with scleral search coils some time later.30 Gain in a healthy person results from the combination of excitation from the excited semicircular canal and disinhibition originating from the contralateral horizontal canal. In VS, unilateral vestibular loss is common. We have shown that gain for the affected side is usually low, and this low gain can contribute to not produce a disinhibition in the turns of the head toward the healthy side. Consequently, when gain for the affected side is low or very low, we can observe a low gain in the healthy side. For this reason, the frequency of RS after head impulses to the nonaffected side was not an unexpected finding. We have seen that the velocity of both the covert (while the head is still moving) and overt (after the head impulse ends) RS is somewhat lower after head impulses to the nonaffected than to the affected side. Furthermore, RS after impulses to the nonaffected side are correlated with gain after impulses to the affected side. We consider that the appearance of overt saccades in the healthy side in patients with a progressive loss of vestibular function in the affected side could be explained by the absence of disinhibition from the affected side in the vestibular system, and that saccades are not a sign of vestibular dysfunction in the healthy side.31
CONCLUSION In conclusion, we have shown that with this modality of evaluation the detection of the vestibular deficit and its consequences in the VOR are superior to the Laryngoscope 125: December 2015
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conventional caloric test. Taking into account the low level of discomfort because neither vertigo nor nausea is elicited, contrary to what occurs with the caloric test, this test should be the first line when a vestibulopathy is suspected. Unfortunately, it does not provide a pathognomonic sign, but the findings will prompt more indepth investigations. In particular, we want to stress the utility of analyzing information from the unaffected side (i.e., a low gain associated with RS). It will also be interesting to know whether this is of interest in the clinical follow-up of these patients should they undergo surgical treatment or remain in a wait-and-see program.
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