Diagnostic Value of Prolonged Latencies in the Vestibular Evoked Myogenic Potential

ORIGINAL ARTICLE Diagnostic Value of Prolonged Latencies in the Vestibular Evoked Myogenic Potential

Toshihisa Murofushi, MD; Ken Shimizu, MD; Hideki Takegoshi, MD; Po-Wen Cheng, MD

Background: As a parameter for the evaluation of the Intervention: Diagnostic. vestibular evoked myogenic potential (VEMP), amplitude has been used clinically. However, the significance Main Outcome Measures: Click-evoked myogenic po- of latency has not been considered. tentials were recorded with surface electrodes over each sternocleidomastoid muscle. Latencies and amplitudes Objective: To clarify the diagnostic value of latencies of responses were measured. of the VEMP. Results: Vestibular evoked myogenic potentials were ab- Design: We reviewed records of the VEMP of patients sent or decreased in 51% of patients with Meniere dis- with various diseases and compared them with records ease (n=22), 39% with vestibular neuritis (n=9), 77% of healthy volunteers. with acoustic neuroma (n=48), and 25% with multiple sclerosis (3 of 12 sides of 6 patients). Concerning la- Setting: Data were collected from patients in an outpa- tency, patients with Meniere disease or vestibular neu- tient clinic of a tertiary care center and healthy volun- ritis hardly showed any latency prolongation. Four pa- teers. tients with acoustic neuroma showed prolonged p13; all had large tumors. All patients with multiple sclerosis Subjects: Clinical records of 134 patients (61 men and showed prolonged p13. 73 women, aged 20-75 years) were reviewed. Diagnoses were Meniere disease in 43 patients, acoustic neuroma Conclusion: Prolonged latencies of the VEMP suggest in 62 patients, vestibular neuritis in 23 patients, and mul- lesions in the retrolabyrinthine, especially in the ves- tiple sclerosis in 6 patients. Also, 18 healthy volunteers tibulospinal tract. (13 men and 5 women, aged 25-38 years) were en- rolled. Arch Otolaryngol Head Neck Surg. 2001;127:1069-1072

LICK-EVOKED myogenic ever, there are no reports concerning la- potentials on the sterno- tency in other diseases. To clarify the cleidomastoid muscle diagnostic value of VEMP latencies, we re- have been used as a clini- viewed VEMP recordings from patients cal test of the vestibulo- with Meniere disease (MD), vestibular neu- spinalC reflex. This response is known as ritis (VN), acoustic neuroma (AN), and MS the vestibular evoked myogenic poten- and compared their results with those of tial (VEMP).1-3 Although we have mainly healthy subjects. used the amplitude of the first positive- negative response (p13-n23) for the evalu- RESULTS ation of VEMP, we have not used the peak latency (p13 and/or n23). Recently, HEALTHY VOLUNTEERS Shimizu et al4 reported that latencies of p13 From the Department of and n23 were prolonged in 3 patients with Clear responses were obtained on both Otolaryngology, Faculty of multiple sclerosis (MS) who are included sides from all healthy subjects. The Medicine, University of Tokyo, in this study and that latencies could be a mean±SD latencies of p13 and n23 were Tokyo, Japan (Drs Murofushi, Shimizu, Takegoshi, and useful parameter for the evaluation of le- 11.8±0.86 and 20.8±2.2 ms, respec- Cheng); and Department of sions in the vestibulospinal tract. We tively. When we defined the mean laten- Otolaryngology, Far Eastern speculated whether the prolongation of the cies +2 SDs as the upper limits of the nor- Memorial Hospital, Taipei, latencies was pathognomonic for MS or le- mal ranges, the upper limits were 13.5 ms Taiwan (Dr Cheng). sions in the vestibulospinal tract. How- (p13) and 25.2 ms (n23). When the

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 SUBJECTS AND METHODS rotate their heads to the opposite side to the stimulated ear as much as possible to activate the sternocleidomastoid SUBJECTS muscle. Electromyographic activities were monitored on a display during the recording to maintain muscle activi- Clinical records of 134 patients (61 men and 73 women, aged ties at a constant level in each patient. The electromyo- 20-75 years) were reviewed. Diagnoses were MD in 43 pa- graphic signal from the stimulated side was amplified and tients, AN in 62 patients, VN in 23 patients, and MS in 6 pa- bandpass filtered (20-2000 Hz). Rarefaction clicks (0.1 mil- tients. Both MD and VN were diagnosed according to stan- lisecond [ms], 95-dB normal hearing level) were pre- dard neurotologic criteria.2,5,6 Diagnoses of AN were confirmed sented through a headphone (type DR-531, Elega Acous. by neurosurgery. In other words, AN in this article repre- Co Ltd, Tokyo, Japan). The stimulation rate was 5 Hz, and sents vestibular schwannoma. The diagnosis of MS was made the analysis time was 50 ms. The responses to 100 stimuli by standard neurological criteria.7 In patients 11, 12, 13, and were averaged twice. 14, T2-weighted magnetic resonance imaging showed high- We analyzed the amplitude of the first positive- negative peak, p13-n23 ipsilateral to the stimulated ear and intensity lesions in the pontine tegmentum involving the ves- 8 tibular nuclei and vestibulospinal tract bilaterally (Figure 1). the latencies of p13 and n23. The average of 2 runs was In patients 15 and 16, T2-weighted magnetic resonance im- taken for the amplitudes and latencies. aging did not show high-intensity lesions in these areas. Ex- For the evaluation of the amplitude, the percentage cept for patients with MS, patients had unilateral diseases. of VEMP asymmetry (VA) was calculated as 100[(Au−Aa)/ Also, 18 healthy volunteers (13 men and 5 women, aged 25-38 (Aa+Au)], where Au is the p13-n23 amplitude on the un- years) underwent VEMP testing. affected side and Aa is the p13-n23 amplitude on the affected side. In healthy volunteers, the percentage of VA was METHODS evaluated as 100[|Ar−Al|/(Ar+Al)], where Ar is the p13- n23 amplitude on the right and Al is the p13-n23 ampli- The methods for recording VEMPs are described else- tude on the left and |Ar−Al| is the absolute value of (Ar−Al).3 where.2,3 Briefly, surface electromyographic activity was re- As parameters of the latency, we measured the peak corded in the supine patient from symmetrical sites over latencies of p13 and n23. p13 is the first positive peak of the upper half of each sternocleidomastoid muscle, with a VEMPs, and n23 is the first negative peak following p13.8 reference electrode on the lateral end of the upper ster- We defined the latency as the time from the onset of the num. During recording, the patients were instructed to stimulus to the peak (Figure 2).

Latency of n23

R L

Latency of p13

Onset of Click 50 µV

Figure 1. Parameters of the latency measured. 10 ms

Figure 2. A T2-weighted magnetic resonance image of patient 14 latency of p13 or n23 was longer than the mean latency (a 50-year-old man with multiple sclerosis) showing high-intensity +2 SDs of healthy volunteers, we regarded the latency as lesions in the pontine tegmentum involving the vestibular nuclei and prolonged. vestibulospinal tract bilaterally. Because the mean±SD of the percentage of VA was 12.5%±8.7%, the upper limit was 30.0%. When the percentage of VA was greater than the mean +2 SDs of healthy (Figure 3). Concerning latencies, only 1 patient showed volunteers, we regarded the amplitude of the smaller side prolongation of p13 (14.0 ms) (Figure 4). None of the as decreased. patients with MD showed prolongation of n23.

PATIENTS Vestibular Neuritis

Meniere Disease Nine (39%) of the 23 patients showed absence of p13- n23 on the affected side, and 14 showed normal re- Fifteen of the 43 patients showed absence of p13-n23 on sponses (Figure 3). Concerning latencies, only 1 of the the affected side, 7 showed decreased responses, and 21 14 patients showed prolonged p13 (13.7 ms) (Figure 4). showed normal responses. In other words, 22 (51%) of None of the patients with VN showed prolongation of 43 showed abnormal amplitudes on the affected side n23.

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 70 Absent Table 1. Patients With Acoustic Neuroma Decreased and Prolonged p13 and/or n23* 60 Normal

50 Patient No./ p13, n23, I-V (ABR), Tumor Sex/Age, y Amplitude ms ms ms Size, cm 40 1/F/51 Normal 14.9 31.2 4.92 2 2/M/54 Decreased 14.6 21.2 Only wave I 3 30 3/M/43 Normal 14.4 27.4 5.2 2 Patients, No. 4/M/48 Decreased 15 26 5.48 2 20 *Four (17%) of the 23 patients with acoustic neuroma showed prolonged 10 p13. All had large tumors. I-V (ABR) indicates interpeak interval between waves I and V (normal, Ͻ4.4 ms). Patient 2 showed only wave I. Tumor size 0 is the length of the tumor protruding from the porus of the internal auditory MD VN AN meatus. Boldface values indicate prolonged latencies.

Figure 3. Amplitudes of p13-n23 on the affected side. Responses were absent or decreased in 22 (51%) of the 43 patients with Meniere disease (MD), 9 (39%) of the 23 patients with vestibular neuritis (VN), and 48 (77%) 22.6 ms of the 62 patients with acoustic neuroma (AN).

30 Left Prolonged Normal 25

12.3 ms 50 µV 20

27.4 ms 15 10 ms No.

10 Right 5

0 MD VNAN MS

Figure 4. Latencies of p13 patients with Meniere disease (MD) or vestibular 14.4 ms neuritis (VN) hardly showed any prolonged p13. Among patients with acoustic neuroma (AN), 4 patients showed prolonged p13. All had large Figure 5. Vestibular evoked myogenic potentials of patient 3 (a 43-year-old tumors. All patients with multiple sclerosis (MS) showed prolongation of p13 man with right-sided acoustic neuroma). Latencies of p13 and n23 on the if they showed any response. No. represents the number of patients in the right were prolonged significantly. MD, VN, and AN groups and the number of sides in the MS group.

Acoustic Neuroma (Vestibular Schwannoma) tion of p13 had large tumors (Table 1). Prolongation of p13 latency was significantly greater in the group of large Thirty-nine of the 62 patients showed absence of re- tumors than the group of small tumors (Fisher exact test, sponses on the affected side, 9 showed decreased re- PϽ.05). sponses, and 14 showed normal responses. In other words, 48 patients (77%) showed abnormal amplitudes (Fig- Multiple Sclerosis ure 3). Concerning latencies, 4 (17%) of the 23 patients with responses showed prolongation of p13 (Figure 4). Among 12 sides of the 6 patients with MS, 3 sides showed Three of the 4 patients also showed prolongation of n23 absence of responses. All of the other sides (9 sides) (Table 1, Figure 5). showed prolongation of p13, and 4 showed prolonga- We classified patients into 2 groups according to their tion of n23 (Table 2, Figure 4). tumor sizes. Twenty-nine patients had small tumors, which protruded from the porus of the internal audi- STATISTICAL ANALYSES tory meatus less than 2 cm. Among the 29 patients, 16 showed absent VEMP, 4 showed decreased VEMP, and The mean latencies and SDs of p13 and n23 are summa- 9 showed normal VEMP. None of them showed prolon- rized in Table 3. Concerning latencies of p13 and n23, gation of the latency of p13 or n23. Thirty-three pa- significant differences were found among 5 groups (con- tients had large tumors, which protruded from the po- trol, MD, VN, AN, and MS) (PϽ.001, 1-way analysis of rus of the internal auditory meatus equal to or more than variance). Significant differences of p13 latencies were 2 cm. Among the 33 patients, 23 showed absent VEMP, found between the MS group and each of the other 4 5 showed decreased VEMP, and 5 showed normal am- groups (PϽ.001, Scheffe´ test). Significant differences of plitudes of VEMP. All 4 patients who showed prolonga- n23 latencies were also found between the MS group and

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 plete damage in the inferior vestibular nerve, resulting Table 2. Latencies of Patients With Multiple Sclerosis* in absence of the VEMP, whereas in other patients the inferior vestibular nerve could be spared as reported by Patient No./Sex/Age, y Side p13, ms n23, ms Murofushi et al2 and Fetter and Dichgans.11 In other words, 11/F/30 L 19.8 29.2 patients with VN may have complete damage or no dam- R 16.7 26.9 age to the inferior vestibular nerve. Second, damage only 12/F/36 L 16.5 23.1 to the vestibular nerve may be insufficient for VEMP la- R 15.3 20.8 13/M/34 L 16.6 24.9 tency prolongation beyond the normal range. In fact, all R 15 23.9 patients with AN who showed latency prolongation had 14/M/50 L NR NR large tumors that compressed the brainstem. The most R 14 20 marked findings were obtained in patients with MS. All 15/F/33 L 21.2 28.2 subjects showed latency prolongation if they showed any RNRNR responses. These results suggest that brainstem lesions, 16/F/46 L NR NR especially those in the vestibulospinal tract, are re- R 20.9 29.1 quired for the prolongation of p13. *Except for the 3 sides that showed no responses, all sides showed From the practical viewpoint, p13 showed prolon- prolongation of p1. Patients 11, 12, and 13 were described by Shimizu et al.4 gation of the latency more frequently than n23. As we Boldface values indicate prolonged latencies. NR indicates no response. showed, the SD of n23 was greater than that of p13, resulting in a wider normal range of n23 than p13. Therefore, p13 is a better parameter for evaluation of Table 3. Mean Latencies of p13 and n23 the latency of VEMP. In conclusion, prolonged VEMP latencies, espe- Mean ± SD Latency, ms cially prolonged p13, would strongly suggest lesions in Group* No. p13 n23 the vestibulospinal tract, although they are not pathognomonic for MS. Control 36 11.8 ± 0.86 20.8 ± 2.2 MD 28 11.9 ± 1.1 20.6 ± 1.5 VN 14 12.0 ± 0.81 21.2 ± 1.8 Accepted for publication March 20, 2001. AN 23 12.4 ± 1.3 21.8 ± 2.9 This study was supported by a research grant from MS 9 17.3 ± 2.6 25.1 ± 2.6 the Intractable Diseases Fund (Vestibular Disorders) of the Ministry of Health and Welfare, Tokyo, Japan. *MD indicates Meniere disease; VN, vestibular neuritis; AN, acoustic neuroma; and MS, multiple sclerosis. Corresponding author and reprints: Toshihisa Murofushi, MD, Department of Otolaryngology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo each of the other 4 groups (PϽ.001 for control, PϽ.001 113-8655, Japan (e-mail: [email protected]). for MD, P=.006 for VN, and P=.02 for AN, Scheffe´ test).

REFERENCES COMMENT

For clinical evaluation of VEMP, amplitude has been 1. Halmagyi GM, Curthoys IS, Colebatch JG. New tests of vestibular function. mainly used.1-3 In patients with the Tullio phenom- Baillieres Clin Neurol. 1994;3:485-500. enon, the threshold has also been used for evalua- 2. Murofushi T, Halmagyi GM, Yavor RA, Colebatch JG. Absent vestibular evoked 9,10 myogenic potentials in vestibular neurolabyrinthitis. Arch Otolaryngol Head Neck tion. The latency is a useful parameter in other types Surg. 1996;122:845-848. of evoked potentials such as auditory brainstem re- 3. Murofushi T, Matsuzaki M, Mizuno M. Vestibular evoked myogenic potentials in sponses. However, latency was seldom used for the evalu- patients with acoustic neuromas. Arch Otolaryngol Head Neck Surg. 1998;124: ation of VEMP, although Shimizu et al4 reported that 3 509-512. 4. Shimizu K, Murofushi T, Sakurai M, Halmagyi GM. Vestibular evoked myogenic patients with MS showed prolongation of p13 latency. potentials in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2000;69:276- It was not yet clear if prolonged VEMP latencies are pa- 277. thognomonic for MS. 5. Committee on Hearing and Equilibrium. Committee on Hearing and Equilibrium In this study, we reviewed the results of VEMPs in guidelines for the diagnosis and evaluation of therapy in Meniere’s disease. patients with MD, VN, AN, and MS. Meniere disease is a Otolaryngol Head Neck Surg. 1995;113:181-185. 6. Strupp M, Brandt T. Vestibular neuritis. Adv Otorhinolaryngol. 1999;55:111- representative disease of labyrinthine lesions, and VN is 136. a representative disease of the vestibular nerve. Acous- 7. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple scle- tic neuroma is a disease in which the vestibular nerve and rosis: guidelines for research protocols. Ann Neurol. 1983;13:227-231. brainstem can be involved, whereas MS is a representa- 8. Colebatch JG, Halmagyi GM, Skuse NF. Myogenic potentials generated by a click-evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry. 1994;57: tive disease of the central nervous system. 190-197. In this study, patients who had MD hardly showed 9. Colebatch JG, Day BL, Bronstein AM, et al. Vestibular hypersensitivity to clicks any prolongation of VEMP latency, whereas many pa- is characteristic of the Tullio phenomenon. J Neurol Neurosurg Psychiatry. 1998; tients showed decreased amplitudes or absent re- 65:670-678. sponses. It is unlikely that prolonged VEMP latencies are 10. Brantberg K, Bergenius J, Tribukait A. Vestibular-evoked myogenic potentials in patients with dehiscence of the superior semicircular canal. Acta Otolaryngol a sign of inner ear lesions. Patients with VN did not show (Stockh). 1999;119:633-640. latency prolongation either. To explain this, we can con- 11. Fetter M, Dichgans J. Vestibular neuritis spares the inferior division of the ves- sider 2 possibilities. First, some patients may have com- tibular nerve. Brain. 1996;119:755-763.

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