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Otology & Neurotology 38:118–122 2016, Otology & Neurotology, Inc.

Tinnitus Suppression After Auditory Brainstem Implantation in Patients With Neurofibromatosis Type-2

Daniel S. Roberts, y Steve Otto, zBrian Chen, y Kevin A. Peng, § jj Marc S. Schwartz, y Derald E. Brackmann, and yJohn W. House

Division of Otolaryngology-Head and Neck Surgery, University of Connecticut School of Medicine, Farmington, Connecticut; yHouse Clinic and House Ear Institute, Los Angeles, California; zDepartment of Otolaryngology-Head and Neck Surgery, William Beaumont Army Medical Center, El Paso, Texas; §House Clinic, Neurosurgery, Los Angeles, California; and jjHuntington Medical Research Institutes, Pasadena, California

Objective: To evaluate whether an auditory brainstem implant (ABI) can impact levels of tinnitus in neurofibroma- tosis type-2 (NF2) patients who have undergone translabyr- inthine craniotomy for vestibular schwannoma (VS) removal and to evaluate the burden of tinnitus in these patients. Study Design: A retrospective cas e series and patient survey. Setting: Tertiary neurotologic referral center. Patients: NF2 patients who underwe nt translabyrinthine removal of VS and ABI placement between 1994 and 2015. Interventions: A survey, retrospective review and two validated tinnitus handicap questionnaires (tinnitus handicap inventory [THI] and tinnitus visual analogue scale [VAS]) were used to characterize the degree of tinnitus in NF2 patients and whether an ABI can alter tinnitus levels. Main Outcome Measures(s): Survey results, THI and VAS scores. Results: One hundred twelve ABI users were contacted and 43 patients (38.3)% responded to our survey. Tinnitus was

reported in 83.7% of patients. The THI score for responders was 17.8 20.5 standard deviation (SD). For survey partici- pants, the ABI reduced tinnitus levels (mean VAS: Off ¼ 3.5; 3.5; On 1-h ¼ 2.1; p ¼ 0.048). For patients who subjectively reported that the ABI reduced tinnitus loudness, tinnitus levels were immediately reduced on ABI activation and after 1 hour of use (mean VAS: Off ¼ 4.8; On ¼ 2.4; On 1-h ¼ 1.8; p < 0.01). Suppression did not continue after the device was turned off. Audiological performance with the ABI did not correlate with tinnitus suppression. Conclusion: NF2 patients who have undergone removal of VS have a significant tinnitus handicap and benefit from tinnitus suppression through utilization of an ABI possibly through masking or electrical stimulation of the auditory brainstem. Key Words: Acoustic neuroma Auditory brainstem implantation NF2 Tinnitus Vestibular schwannoma.

Otol Neurotol 38: 118–122, 2017.

Electrical stimulation of the auditory system for tinnitus suppression is an area of active investigation (1). Cochlear implantation (CI) reproducibly causes tinnitus suppression in a majority of patients (2). While subjective tinnitus is likely a multifactorial entity, it is hypothesized that tinnitus arises from changes in neural circuitry caused by a reduction in auditory input. Positron emission tomography (PET) has shown altered metabolic brain activity in the auditory cortex and recent evidence suggests roles for the limbic, frontal, and parietal brain in the pathophysiology of chronic tinnitus (3).

Address correspondence and reprint requests to John W. House, M.D., 2100 West 3rd Street, Los Angeles, CA 90057; E-mail: jhouse@houseclinic.com Marc S. Schwartz is a consultant and receives grant support from Cochlear Corporation for unrelated projects. All other authors disclose no conflicts of interest. DOI: 10.1097/MAO.0000000000001230

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The development of the auditory brainstem implant (ABI) provided a means of bypassing the cochlea and auditory nerve to electrically stimulate the second order neurons of the cochlear nucleus. The device was origin- ally designed for patients with neurofibromatosis type-2 (NF2), and the vast majority of patients implanted to date are patients with NF2 and bilateral vestibular schwannomas (VS). Since William Hitselberger and William House first performed the ABI in 1979, more than 1,250 patients have been implanted worldwide with 310 implants occurring at our institution. Early results suggested a role of tinnitus suppression after ABI implan- tation, where tinnitus reduction occurred in six of seven patients who reported daily use of the device; however, long-term outcomes using validated measures of tinnitus handicap have not been reported to date (4). The hypothesis of this study is that ABIs reduce tinnitus levels in NF2 patients. We investigated if ABIs influence tinnitus levels in NF2 patients who have received an ABI after VS resection.

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TABLE 1. Patient characteristics

 

(n ¼ 43)

Age (yrs, mean [SD]) Age at ABI placement (yrs, mean [SD]) Follow-up to ABI implantation (mo, mean [SD]) Follow-up to audiological testing (mo, mean [SD]) Sex (% male)

46.7 (15.6)

36.1 (14.7)

131.2 (64.4)

43.3 (39.2)

37.2%

NF2

100%

Bilateral ABIs (%) Bilateral acoustic neuroma surgery (%) ABI usage (hours per day) a 0 hours 0–2 hours 2–4 hours 4–8 hours 8–12 hours >12 hours

5 (11.6)

86.8% a

5 (13.1)

0 (0)

1 (2.6)

1 (2.6)

8 (21.1)

23 (60.5)

a Thirty eight patients reporting. ABI indicates auditory brainstem implant; SD, standard deviation.

METHODS

A retrospective chart review and patient survey were performed of NF2 patients undergoing translabyrinthine removal of VS and placement of an ABI with the goal of hearing restoration between 1994 and 2015. Institutional review board approval was obtained (St. Vincent Medical Center, Los Angeles, CA, 15-012 J. House). The multichannel ABI in use at our center is the 21-electrode system (Cochlear Corp, Englewood, CO) that has been approved by the US Food and Drug Administration. Trans- labyrinthine resection of VS and placement of ABI are described elsewhere (5). Questionnaires were mailed to patients to assess their levels of tinnitus. The questionnaire contained a set of questions regarding patient demographics, tinnitus symptomatology, and ABI utilization (see results Table 1). A tinnitus handicap inventory (THI) was also included to quantify the overall levels of tinnitus (6,7). The THI is a well-validated and widely used self-report measure with 25 questions. Each answer is given a score of 0 (never), 2 (sometimes), or 4 (always), for a total score of 100. THI scores may be graded as slight (0–16), mild

Awake from sleep in morning, rank severity of nnitus.

ABI OFF

A

Turn on ABI.

Immediately rank severity of nnitus.

ABI ON

Wait for 1 hour a er your ABI is on.

Rank the severity of your nnitus. ABI ON

Turn ABI Off. Wait for 1 hour.

Rank the severity of your nnitus. ABI OFF

B

hour. Rank the severity of your nnitus. ABI OFF B C V A S 10 9

C

V

A

S

10

9

8

7

6

5

4

3

2

1

0

p=0.048 p<0.01 p<0.01 p<0.01 p<0.01
p=0.048
p<0.01
p<0.01
p<0.01
p<0.01

AM (Device Off)

Device On (Immediate)

Device On (1 hr)

Device Off (1 hr)

All pa ents ents

TinnitusDevice On (1 hr) Device Off (1 hr) All pa ents present, perceived benefit from ABI

present,

perceived

benefit from

ABI

FIG. 1. Modulation of tinnitus levels with an ABI. A, Patients were asked to rank tinnitus levels in four conditions with the ABI on or off according to the diagram ( B), visual analogue scale (VAS) used to score tinnitus levels ( C ), quantification of tinnitus levels. Data are mean VAS scores SEM. Dark bars are all patients responding (n ¼ 33). Light bars are for patients who thought the ABI reduced tinnitus loudness subjectively (n ¼ 16). ABI indicates auditory brainstem implant; SEM, standard error of mean.

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D. S. ROBERTS ET AL.

(18–36), moderate (38–56), severe (58–76), and catastrophic (78–100) (6,7). Thus, the higher the THI score, the greater the handicap. Finally, levels of tinnitus, while using (and not using) the ABI were then evaluated using the tinnitus visual analogue scale (VAS) at four sequential determinations. The VAS is a 10 cm visual scale (0–10) where 0 describes no tinnitus, 10 describes the worst possible tinnitus (Fig. 1A) that is easily applied to different experimental conditions and correlated with THI (8). The four sequential scenarios are described (Fig. 1B):

(1) After you awake from sleep in the morning, immedi- ately rank your tinnitus on the following scale with your ABI off (0 describes no tinnitus, 10 describes the worst possible tinnitus).

Turn on your ABI. Then, immediately rank the severity

of your tinnitus. Circle a number. (0 describes no tinnitus, 10 describes the worst possible tinnitus). (3) Wait for 1 hour after your ABI is on. Then, rank the

severity of your tinnitus. Circle a number. (0 describes no tinnitus, 10 describes the worst possible tinnitus). Turn off your ABI. Wait for 1 hour after your ABI is off. Then, rank the severity of your tinnitus. Circle a number. (0 describes no tinnitus, 10 describes the worst possible tinnitus).

(4)

(2)

Patients were asked to gauge the level of background noise during these tasks. The listening environment (background noise) was designated as low, moderate, or high.

Audiometric Analysis

Speech perception performance was determined for each patient using the Northwestern University-Children’s Percep- tion of Speech (NU-CHIPS) word test, a 4-choice monosyllabic word test given in the sound-only mode (9). The best post- implantation performance was recorded and compared with tinnitus levels using these above described measures.

Data Analysis

Data were extracted directly from patient surveys and medical records. Survey data w ere reported for all patients despite incomplete survey responses for some patients. Microsoft Excel (Redmond, WA), and SPSS (Armonk, NY) were used for analysis. Both pa rametric and nonparametric statistics were used, includi ng correlation and analysis of variance for continuous/interval level data and Games-Howell post hoc test. Criterion for statistical significance was set at p < 0.05.

RESULTS

From 1994 to 2015, 279 patients underwent ABI placement at our institution. All patients implanted with the multichannel 21-electrode system (Cochlear Corp, Englewood, CO) with known contact information who resided in the United States and who were adults were contacted (n ¼ 133). One hundred-twelve patients received our patient survey with 43 patients (38.3%) responding. Patient characteristics are shown in Table 1. Tinnitus was present in 83.7% of patients and the duration of tinnitus was substantial (18.8 11.7 SD years). More commonly, tinnitus was perceived in both ears (74.4%). Patients were unable to localize tinnitus in 15.4% of cases. Tinnitus was isolated to the right or left

TABLE 2. ABI utilization and characteristics of tinnitus modulation

 

Yes

No

Does ABI provide hearing benefit? Usable hearing without ABI (%)? Does ABI change tinnitus loudness? Does ABI reduce tinnitus loudness? Does ABI increase tinnitus loudness? Does ABI change quality of tinnitus? (Example changes the frequency) If your tinnitus is reduced by your ABI, does the device need to be on to have a reduction?

35 (81.4)

8 (18.6)

5 (11.9)

37 (88.1)

20 (55.6)

16 (44.4)

20 (54.1)

17 (45.9)

2 (5.4)

35 (94.6)

18

(47.4)

20 (52.6)

14

(60.9)

9 (39.1)

How long is your tinnitus reduced after you turn your ABI off?

NA

16 (66.7)

0 hour

0 (0)

<1 hour

2 (8.3)

1–2 hours

3 (0.13)

2–4 hours

1 (4.2)

4–12 hours

2 (8.3)

>12 hours

0 (0)

(%) indicates percent; ABI, auditory brainstem implant; SD, standard deviation.

ear in 10.2% of cases. THI score for all participants was 17.8 20.5 SD. Mean VAS score with the device off was 3.7 2.5 SD. A series of survey questions were used to investigate how the ABI is used among responders and if tinnitus levels were modulated by the device (Table 2). 81.4% of patients described hearing benefits from the ABI and 88.1% had no useable hearing without the device. Tin- nitus loudness was modulated in 55.6% and a reduction of tinnitus loudness was reported in 54.1%. Notably, tinnitus loudness was subjectively increased in 5.4% by the ABI. For patients who had a reduction in tinnitus levels, the majority (60.9%) thought that the device

needed to be active for tinnitus suppression. Eight of forty-three (18.6%) patients describe some subjective persistent degree of tinnitus suppression after the device was turned off with suppression lasting less than l to 12 hours. To experimentally investigate levels of tinnitus while using and not using the ABI, the tinnitus VAS was used in four conditions described in Fig. 1A. For all patients completing this component of our survey (n ¼ 32), tin- nitus was reduced when the device was turned on for 1 hour (mean VAS: Off ¼ 3.5; On 1-h ¼ 2.1; p ¼ 0.048) (Fig. 1C). For patients who thought the ABI reduced tinnitus loudness subjectively, the ABI reduced tinnitus scores immediately on activation and after 1 hour of use (mean VAS: Off ¼ 4.8; On ¼ 2.4; On 1-h ¼ 1.8; Off 1-h ¼ 4.8 p < 0.01) (Fig. 1C). Suppression did not persist after the device was off for 1 hour. During these tasks, the listening environment (background noise) was self-reported in 20 of 43 patients (46.5%) and designated as low, moderate, or high. Eight of 20 patients described

a low level of background noise while 12 of 20 reported

a moderate level.

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Lastly, we investigated whether audiological per- formance with the ABI and device utilization related to levels of tinnitus suppression. Best audiological performance using the NU-CHIPS test had no corre- lation to THI scores ( R 2 ¼ 0.006). When only patients who used the ABI for some period of the day were considered, the length of time since implantation had no influence on THI scores ( R 2 ¼ 0.03). THI scores were then stratified by daily ABI usage. Higher daily ABI usage was not associated with differences in THI scores.

DISCUSSION

Our data represent a single institution series character- izing levels of tinnitus in NF2 patients with ABIs. Importantly, we illustrate that tinnitus levels may be suppressed by utilization of an ABI in NF2 patients who have undergone translabyrinthine craniotomy for VS removal. Our data are consistent with two other studies that have noted some degree of tinnitus suppression among NF2 ABI recipients. In a study of 10 NF2 patients who received an ABI at the time of translabyrinthine surgery for removal of an acoustic neuroma from our institution, six of seven who reported daily use of their ABIs noted some suppression of their tinnitus (4). In another study of 20 patients with NF2 receiving the ABI through a retro- sigmoid approach, the majority achieved some tinnitus suppression (10). However, meaningful conclusions could not be deduced from these studies because vali- dated measures of tinnitus handicap where not used in the assessment of outcomes. Findings in the current study suggest tinnitus was reduced when the device was turned on for 1 hour. For patients who thought the ABI reduced tinnitus loudness subjectively, the ABI reduced tinnitus VAS scores immediately on activation and after 1 hour of use. Suppression did not persist after the device was off for 1 hour. Together, these data illustrate that suppression occurs rapidly after the device is activated and does not persist for greater than 1 hour after the device is turned off. A logical question is whether these changes represent a meaningful and clinically significant level of tinnitus suppression. Amoodi et al. (11) showed that tinnitus suppression mediated by CI leads to a reduction of THI by 16 points in one series (preoperative THI 36.18; 12 months after CI, 20.18). Tinnitus reduction did not correlate with audiological performance, how- ever, tinnitus reduction did correlate with improved quality-of-life (QOL) domains. These data suggest that a 16-point change in THI is clinically significant and may impact QOL. We report reduced VAS scores by 1.4 (3.5–2.1) for all patients completing the survey. For patients with tinnitus and a subjective improvement when using the ABI, VAS scores were reduced three points (4.8–1.8). A three-point change in VAS is estimated to correlate with approximately an 18-point change in THI

(8), suggesting clinically significant findings in some patients relating to improved QOL through tinnitus suppression. However, QOL was not directly tested in our study and further studies are needed to make these conclusions. The mechanism by which the ABI may modulate tinnitus can only be speculated. A fundamental question is whether tinnitus suppression occurs primarily due to masking, or that tinnitus suppression occurs due to electrical stimulation of the auditory brainstem which may alter neurological activity associated with peripheral deafferentation. Evidence supporting a masking mech- anism includes early experience with CI and tinnitus suppression through transcutaneous electrical stimu- lation. Early CI recipients who responded to CI for tinnitus suppression also benefited from a hearing aid for tinnitus masking (12). Shulman noted that the majority of patients who achieved tinnitus suppression with transcutaneous electrical stimulation have pre- viously benefited from tinnitus masking (13). A masking mechanism may account for our findings because the onset of tinnitus suppression occurred immediately with device activation and suppression did not persist after the device is inactivated for 1 hour. A second possibility is that ABIs exert a direct inhibi- tory effect in the auditory system at the level of the brain or brainstem, possibly at the cochlear nucleus, auditory cortex, or inferior colliculus. A plausible electrophysio- logical mechanism suggests that chronic electrical stimu- lation of the deafferented auditory nerve can reverse the downregulation of glycinergic receptor (GlyRalpha1) and glutamic acid decarboxylase (GAD) 67 expression in the central nucleus of inferior colliculus (CIC) (14). These changes or other molecular changes associated with neural plasticity after electrical stimulation could mediate tinnitus suppression. A second report suggests that subjective tinnitus may be controlled by intraco- chlear electrical stimulation, generated by a CI in a participant with single-sided deafness through stimu- lation that is independent of environmental sounds (15). Our survey data show that 39.1% of patients report tinnitus reduction that continues when the ABI is off suggesting residual inhibition of tinnitus. A plausible mechanism includes an alteration of neural plasticity that persists even when the device is off. However, our experimental data suggest that tinnitus suppression requires the device to be on. Further efforts will focus on the question of whether tinnitus suppression after ABI occurs through masking or by altering neural plasticity. Our data report the presence of tinnitus in 83.7% of patients, a prevalence that is consistent with other data in NF2 patients after translabyrinthine removal (16). To our knowledge, our data expand upon our understanding of the severity of tinnitus in this population by establishing levels of tinnitus handicap through the THI and VAS scores. The reported level of THI 17.8 20.5 SD in our NF2 patients is similar to THI 1-year after resection of a unilateral sporadic VS (13.5 19.5 SD) (17). Tinnitus levels are lower when compared with CI patients before

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and after implantation in one series (preoperative THI 36.18; 12 months after CI 20.18) (11). Overall, the established THI for our patients is categorized as mild tinnitus (18). Mild tinnitus is typically masked with environmental sounds and may interfere with sleep but typically is not intrusive to daily activities (18). However, in patients with NF2 with no usable hearing, who accounted for 88.1% of our patients, conventional mask- ing is not an option illustrating the importance of ABIs for tinnitus reduction for some NF2 patients. As with all retrospective and survey studies, there are several caveats with data interpretation. There is the risk of bias from this type of evaluation because we are depending on voluntary survey responses that may under or over-report the incidence and degree of tinnitus severity. Our survey response rate was 38% and partial responses to our survey were present in some cases suggesting possible reporting bias. Additionally, our study design asked patients to rank tinnitus levels while the ABI was on and off, however, we were not able to control for the levels of background noise during these tasks. The degree of tinnitus suppression may indeed vary depending on the level of background noise. 88.1% of our cohort has no useable hearing without the ABI device with variable ABI performance. It may not be possible for our patients to gauge background noise during these tasks. A prospective study at our institution is underway to further characterize our patient population controlling for these variables.

CONCLUSIONS

NF2 patients who have undergone removal of VS have a notable tinnitus handicap. This study shows that tinnitus suppression occurs in NF2 patients implanted with an ABI. In subgroup analyses of patients who reported tinnitus suppression, tinnitus levels were immediately reduced on ABI activation and suppression persisted during use. Suppression did not continue after the device was turned off for 1 hour. Audiological performance, ABI usage, and length of time since implantation did not correlate with tinnitus suppression. These findings show that the auditory brainstem is a target for tinnitus suppression for NF2 patients and suggest that the coch- lear nucleus may be a putative target for tinnitus sup- pression in patients with idiopathic tinnitus.

Acknowledgments: The authors are grateful for our patients who enthusiastically participated in this study.

REFERENCES

1. Arts RA, George EL, Stokroos RJ, Vermeire K. Review: coch- lear implants as a treatment of tinnitus in single-sided deafness. Curr Opin Otolaryngol Head Neck Surg 2012;20:

398–403.

2. Roberts DS, House JW. Tinnitus suppression and cochlear implan- tation.Tinnitus: Diagnosis and Treatment, 2nd ed. New York:

Shulman; 2016.

3. Schecklmann M, Landgrebe M, Poeppl TB, et al. Neural correlates of tinnitus duration and distress: a positron emission tomography study. Hum Brain Map 2013;34:233–40.

4. Soussi T, Otto SR. Effects of electrical brainstem stimulation on tinnitus. Acta Otolaryngol 1994;114:135–40.

5. Schwartz MS, Otto SR, Shannon RV, Hitselberger WE, Brackmann DE. Auditory brainstem implants. Neurotherapeutics 2008;5:

128–36.

6. Newman CW, Jacobson GP, Spitzer JB. Development of the tinnitus handicap inventory. Arch Otolaryngol Head Neck Surg

1996;122:143–8.

7. Newman CW, Sandridge SA, Jacobson GP. Psychometric adequacy of the tinnitus handicap inventory (THI) for evaluating treatment outcome. J Am Acad Audiol 1998;9:153–60.

8. Figueiredo RR, Azevedo AA, Oliveira Pde M. Correlation analysis of the visual-analogue scale and the tinnitus handicap inventory in tinnitus patients. Braz J Otorhinolaryngol 2009;75:

76–79.

9. Elliot LL, Katz DR. The Northwestern University Children’s Per- ception of Speech Test: NU-CHIPS . St Louis: Auditec; 1980.

10. Behr R, Mu¨ ller J, Shehata-Dieler W, et al. The high rate CIS auditory brainstem implant for restoration of hearing in NF-2 patients. Skull Base 2007;17:91–107.

11. Amoodi HA, Mick PT, Shipp DB, et al. The effects of unilateral cochlear implantation on the tinnitus handicap inventory and the influence on quality of life. Laryngoscope 2011;121:1536–40.

12. Berliner KI, Cunningham JK. Tinnitus suppression in cochlear implantation. In: Hazell J, editor. Tinnitus. London: Churchill Livingstone; 1987. pp. 118–30.

13. Shulman A. External electrical stimulation in tinnitus control. Am J Otol 1985;6:110–5.

14. Argence M, Vassias I, Kerhuel L, Vidal PP, de Waele C. Stimu- lation by cochlear implant in unilaterally deaf rats reverses the decrease of inhibitory transmission in the inferior colliculus. Eur J Neurosci 2008;28:1589–602.

15. Zeng FG, Tang Q, Dimitrijevic A, Starr A, Larky J, Blevins NH. Tinnitus suppression by low-rate electric stimulation and its electro- physiological mechanisms. Hear Res 2011;277:61–6.

16. Moffat DA, Lloyd SK, Macfarlane R, et al. Outcome of trans- labyrinthine surgery for vestibular schwannoma in neurofibroma- tosis type 2. Br J Neurosurg 2013;27:446–53.

17. Baguley DM, Humphriss RL, Axon PR, Moffat DA. Change in tinnitus handicap after translabyrinthine vestibular schwannoma excision. Otol Neurotol 2005;26:1061–3.

18. McCombe A, Baguley D, Coles R, McKenna L, McKinney C, Windle-Taylor P, British Association of Otolaryngologists, Head and Neck Surgeons. Guidelines for the grading of tinnitus severity:

the results of a working group commissioned by the British Associ- ation of Otolaryngologists, Head and Neck Surgeons. 1999. Clin Otolaryngol Allied Sci 2001;26:388–93.

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