This research was funded by a Health and Labor Sciences Research Grant for Research on Rare and Intractable Diseases and Comprehensive Research on Disability Health and Welfare from the Ministry of Health, Labour and Welfare of Japan (S.U. 20FC1048, 23FC10149) and Grants-in-Aid from the Japan Agency for Medical Research and Development (AMED) (S.U. 19ek0109363h0002, 21ek0109542h003).

The described procedures were approved by the Institutional Review Board of Shinshu University School of Medicine (Approval no. 4133). The patients provided written informed consent before participating in the study. The reagents, equipment, and software used for this study are listed in the Table of Materials.
1. Preoperative evaluation
<ol>
	<li>Review the series of pure-tone audiograms in patients with residual hearing to ascertain the progression of HL in each case.</li>
	<li>Conduct genetic testing on blood samples obtained from both patients and their family members.</li>
	<li>Recommend to perform next-generation sequencing on a panel of genes associated with HL6,7.</li>
	<li>Conduct imaging tests, such as CT and/or magnetic resonance imaging (MRI). It was recommended that the CT slice thickness be 0.6 mm or less. For MRI, a strength of 1.5 Tesla was deemed sufficient.</li>
	<li>Make predictions regarding future residual acoustic hearing to the best extent possible following the collection of the audiogram series6 and the identification of etiology through imaging and/or genetic analysis.</li>
	<li>Import DICOM data from preoperative CT images into the OTOPLAN software. The software automatically measures the CDL in each case.</li>
	<li>Select the appropriate length of the CI array to cover the region where residual hearing is anticipated to deteriorate in the future. Employ only thin, straight, and flexible electrodes.</li>
	<li>Administer prednisolone orally at a dosage of 0.5-1.0 mg/kg/day beginning 2 days prior to surgery.</li>
</ol>
2. Surgical procedure
<ol>
	<li>Place the patient in the supine position.</li>
	<li>Induce anesthesia using intravenous fentanyl (1-2 &#181;g/kg), propofol (1-2 mg/kg), and rocuronium (0.6 mg/kg). Maintain anesthesia with propofol (3-8 mg/kg/h), remifentanil (0.1-0.2 &#181;g/kg/min), and fentanyl (total: 300-500 &#181;g), without vecuronium, to facilitate neuromuscular monitoring.</li>
	<li>Administer an intravenous infusion of 8 mg of dexamethasone 30 min before making the incision.</li>
	<li>Rotate the patient&#39;s head to 45 degrees during surgery.</li>
	<li>Inject local anesthesia (subcutaneous 0.5% lidocaine with 1:1,00,000 epinephrine) postauricularly.</li>
	<li>Perform a postauricular incision of 5-6 cm (lazy S-shaped) and mastoidectomy with 6.0-4.0 mm cutting bars until reaching the point where the antrum includes the lateral semicircular canal and the short process of the incus6.</li>
	<li>Perform a posterior tympanotomy between the expected facial nerve and chorda tympani using 1.5-2.0 mm diamond bars.</li>
	<li>Visualize the round window niche and remove the bony overhang of the round window using a low-speed drill with a 1.0-1.5 mm diamond bar, exposing the round window membrane.</li>
	<li>Sufficiently open the round window membrane using a pick and carefully insert the electrode slowly for over 3 min.</li>
	<li>Perform X-ray and audiograms after completing the electrode insertion.</li>
</ol>
3. Postoperative evaluation
<ol>
	<li>Administer intravenous dexamethasone at 8 mg/day, 4&#160;mg/day, and 4 mg/day for 3 days following surgery.</li>
	<li>Measure unaided auditory thresholds 6 months after the initial activation, and assess the HP rate using the classification provided by Skarzynski et al.20.</li>
	<li>Optimize map settings using a software tool based on the results of the postoperative audiogram and patient&#160;preferences.</li>
</ol>

Hearing Preservation with Long Electrodes in Electric-Acoustic Stimulation

<ol>
	<li>Von Ilberg, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electric-acoustic+stimulation+of+the+auditory+system.+New+technology+for+severe+hearing+loss.">Electric-acoustic stimulation of the auditory system. New technology for severe hearing loss.</a> ORL J Otorhinolaryngol Relat Spec. 61 (6), 334-340 (1999).</li><li>Gstoettner, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+electrode+for+residual+hearing+preservation+in+cochlear+implantation:+First+clinical+results.">A new electrode for residual hearing preservation in cochlear implantation: First clinical results.</a> Acta Otolaryngol. 129 (4), 372-379 (2009).</li><li>Moteki, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Feasibility+of+hearing+preservation+for+residual+hearing+with+longer+cochlear+implant+electrodes.">Feasibility of hearing preservation for residual hearing with longer cochlear implant electrodes.</a> Acta Otolaryngol. 138 (12), 1080-1085 (2018).</li><li>Usami, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Achievement+of+hearing+preservation+in+the+presence+of+an+electrode+covering+the+residual+hearing+region.">Achievement of hearing preservation in the presence of an electrode covering the residual hearing region.</a> Acta Otolaryngol. 131 (4), 405-412 (2011).</li><li>Usami, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hearing+preservation+and+clinical+outcome+of+32+consecutive+electric+acoustic+stimulation+(EAS)+surgeries.">Hearing preservation and clinical outcome of 32 consecutive electric acoustic stimulation (EAS) surgeries.</a> Acta Otolaryngol. 134 (7), 717-727 (2014).</li><li>Yoshimura, H., Moteki, H., Nishio, S. Y., Usami, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electric-acoustic+stimulation+with+longer+electrodes+for+potential+deterioration+in+low-frequency+hearing.">Electric-acoustic stimulation with longer electrodes for potential deterioration in low-frequency hearing.</a> Acta Otolaryngol. 140 (8), 632-638 (2020).</li><li>Yoshimura, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetic+testing+has+the+potential+to+impact+hearing+preservation+following+cochlear+implantation.">Genetic testing has the potential to impact hearing preservation following cochlear implantation.</a> Acta Otolaryngol. 140 (6), 438-444 (2020).</li><li>Van de Heyning, P. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systematic+literature+review+of+hearing+preservation+rates+in+cochlear+implantation+associated+with+medium-+and+longer-length+flexible+lateral+wall+electrode+arrays.">Systematic literature review of hearing preservation rates in cochlear implantation associated with medium- and longer-length flexible lateral wall electrode arrays.</a> Front Surg. 9, 893839 (2022).</li><li>Buchman, C. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+cochlear+implant+insertion+depth+on+performance:+A+prospective+randomized+trial.">Influence of cochlear implant insertion depth on performance: A prospective randomized trial.</a> Otol Neurotol. 35 (10), 1773-1779 (2014).</li><li>Buchner, A., Illg, A., Majdani, O., Lenarz, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Investigation+of+the+effect+of+cochlear+implant+electrode+length+on+speech+comprehension+in+quiet+and+noise+compared+with+the+results+with+users+of+electro-acoustic-stimulation,+a+retrospective+analysis.">Investigation of the effect of cochlear implant electrode length on speech comprehension in quiet and noise compared with the results with users of electro-acoustic-stimulation, a retrospective analysis.</a> PLoS One. 12 (5), e0174900 (2017).</li><li>Canfarotta, M. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+influence+of+electrode+array+length+on+speech+recognition+in+cochlear+implant+users.">Long-term influence of electrode array length on speech recognition in cochlear implant users.</a> Laryngoscope. 131 (4), 892-897 (2021).</li><li>Nassiri, A. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hearing+preservation+outcomes+using+a+precurved+electrode+array+inserted+with+an+external+sheath.">Hearing preservation outcomes using a precurved electrode array inserted with an external sheath.</a> Otol Neurotol. 41 (1), 33-38 (2020).</li><li>O'Connell, B. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrode+location+and+angular+insertion+depth+are+predictors+of+audiologic+outcomes+in+cochlear+implantation.">Electrode location and angular insertion depth are predictors of audiologic outcomes in cochlear implantation.</a> Otol Neurotol. 37 (8), 1016-1023 (2016).</li><li>Moteki, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+results+of+hearing+preservation+cochlear+implant+surgery+in+patients+with+residual+low+frequency+hearing.">Long-term results of hearing preservation cochlear implant surgery in patients with residual low frequency hearing.</a> Acta Otolaryngol. 137 (5), 516-521 (2017).</li><li>Von Ilberg, C. A., Baumann, U., Kiefer, J., Tillein, J., Adunka, O. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electric-acoustic+stimulation+of+the+auditory+system:+A+review+of+the+first+decade.">Electric-acoustic stimulation of the auditory system: A review of the first decade.</a> Audiol Neurootol. 16, 1-30 (2011).</li><li>Ariyasu, L., Galey, F. R., Hilsinger, R., Byl, F. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Computer-generated+three-dimensional+reconstruction+of+the+cochlea.">Computer-generated three-dimensional reconstruction of the cochlea.</a> Otolaryngol Head Neck Surg. 100 (2), 87-91 (1989).</li><li>Danielian, A., Ishiyama, G., Lopez, I. A., Ishiyama, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Morphometric+linear+and+angular+measurements+of+the+human+cochlea+in+implant+patients+using+3-dimensional+reconstruction.">Morphometric linear and angular measurements of the human cochlea in implant patients using 3-dimensional reconstruction.</a> Hear Res. 386, 107874 (2020).</li><li>Kawano, A., Seldon, H. L., Clark, G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Computer-aided+three-dimensional+reconstruction+in+human+cochlear+maps:+Measurement+of+the+lengths+of+organ+of+Corti,+outer+wall,+inner+wall,+and+Rosenthal's+canal.">Computer-aided three-dimensional reconstruction in human cochlear maps: Measurement of the lengths of organ of Corti, outer wall, inner wall, and Rosenthal's canal.</a> Ann Otol Rhinol Laryngol. 105 (9), 701-709 (1996).</li><li>Rask-Andersen, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+cochlea:+Anatomical+characteristics+and+their+relevance+for+cochlear+implantation.">Human cochlea: Anatomical characteristics and their relevance for cochlear implantation.</a> Anat Rec (Hoboken). 295 (11), 1791-1811 (2012).</li><li>Skarzynski, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Towards+a+consensus+on+a+hearing+preservation+classification+system.">Towards a consensus on a hearing preservation classification system.</a> Acta Otolaryngol Suppl. 564, 3-13 (2013).</li><li>Yoshimura, H., Watanabe, K., Nishio, S. Y., Takumi, Y., Usami, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determining+optimal+cochlear+implant+electrode+array+with+OTOPLAN.">Determining optimal cochlear implant electrode array with OTOPLAN.</a> Acta Otolaryngol. 143 (9), 748-752 (2023).</li><li>Skarzynska, M. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preservation+of+hearing+following+cochlear+implantation+using+different+steroid+therapy+regimens:+a+prospective+clinical+study.">Preservation of hearing following cochlear implantation using different steroid therapy regimens: a prospective clinical study.</a> Med Sci Monit. 24, 2437-2445 (2018).</li><li>Geerardyn, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+histology+after+structure+preservation+cochlear+implantation+via+round+window+insertion.">Human histology after structure preservation cochlear implantation via round window insertion.</a> Laryngoscope. 134 (2), 945-953 (2023).</li><li>Campbell, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intraoperative+real-time+cochlear+response+telemetry+predicts+hearing+preservation+in+cochlear+implantation.">Intraoperative real-time cochlear response telemetry predicts hearing preservation in cochlear implantation.</a> Otol Neurotol. 37 (4), 332-338 (2016).</li></ol>

The authors declare no conflicts of interest.

Identifying the etiology of HL in the preoperative evaluation is crucial for predicting the future audiogram in each case. In our earlier study, pathogenic variants in the CDH23, ACTG1, Mit1555A&#62;G, MYO7A, MYO15A, SLC26A4, and TMPRSS3 genes were frequently identified in patients with high-frequency HL7. In most of these patients, the residual hearing gradually deteriorated (see CDH23-related HL case in Figure 2). In these cases, the natural course of HL was considered when selecting the CI electrode for broader cochlear coverage.
Determining the length of the CI array required measuring the cochlear duct length (CDL). To facilitate this process, the OTOPLAN software proved to be clinically feasible21. In earlier versions, such as OTOPLAN 3.0, the CDL was manually measured to plot each cochlea&#39;s diameter, width, and height. However, with OTOPLAN 4.0, automatic measurement of the CDL became possible, offering increased convenience for surgeons and minimizing measurement variation. Notably, CT images with a slice thickness of 0.6 mm or less were suitable for the automatic analysis provided by OTOPLAN. Subsequently, the length of the CI array should be selected to achieve the optimal angle of insertion depth (AID) in each case.
To perform a less invasive EAS surgery, pre-, intra-, and post-steroid administration was required to minimize the acute inflammation that could elevate the hearing threshold22. In the near future, to minimize not only acute but also chronic reactions following CI and EAS surgery, the use of dexamethasone-eluting electrodes will be desirable. In addition to steroid administration, flexible lateral-wall electrodes were essential for minimizing trauma to the cochlea. Inserting such electrodes into the cochlea carefully and slowly using the round window approach resulted in minimal invasiveness. To aid in this, performing surgery using exoscopes and endoscopes was useful for generating a clearer field of view and confirming the tiny components of the middle ear. To prevent inducing extensive fibro-osseous tissue formation in the cochlea, the extended round window approach and cochleostomy must be avoided23.
EAS with longer electrodes was useful not only to prepare for the future deterioration of HL but also to offer three types of map strategies. If the inserted electrodes overlap with the residual hearing region, patients with EAS can use ES with or without AS: &#34;EAS (Overlap/ON) map&#34; or &#34;ES-only map.&#34; Alternatively, they can turn off some of the apical contacts and activate the AS: &#34;EAS (Overlap/OFF) map.&#34; If hearing deteriorates, all the contacts can be later switched on to provide better pitch matching (Figure 3). All these findings show that EAS with longer electrodes allows users to optimize maps for more natural hearing.
Herein, it is shown that preoperative preparation and advanced surgical techniques are essential to minimize surgical trauma. Performing the above-named series of pre-and intra-operative procedures allowed patients to benefit from EAS with longer electrodes.




Limitations 
Despite advances in the aforementioned less-invasive surgical procedures, residual hearing still deteriorates in a certain number of patients after CI. Intra-operative monitoring, such as cochlear microphonics (CM), would be clinically feasible to measure cochlear damage during the electrode insertion24. However, how to evaluate EAS with longer electrodes and what to do in the case of certain CM responses, such as a decrease in amplitude, remains unclear to date. Further studies in this area are required.

Conventional cochlear implantation (CI) is a standard treatment for improving hearing ability in patients with severe-to-profound hearing loss (HL). Subsequently, electric-acoustic stimulation (EAS) is used to treat patients with severe high-frequency hearing loss and residual low-frequency hearing1. In such patients, preserving the residual acoustic hearing is important to achieve better speech perception in noise, sound localization, and improved sound quality when listening to music2. To address this,&#160;the use of&#160;shorter electrodes in EAS patients has been preferred to avoid interfering with the residual function in the acoustic region of the cochlea. However, our earlier studies3,4,5,6&#160;documented that even in EAS cases, less invasive CI surgery combined with thin, straight, and flexible &#34;longer&#34; electrodes enabled the preservation of residual hearing. Additionally, we reported that hearing preservation was unrelated to the length of the inserted cochlear implant electrode7, consistent with the systematic review8.
In patients who underwent conventional CI, longer electrodes led to better speech perception9,10,11&#160;as longer electrodes provide broader cochlear coverage and better place-pitch matching. Similarly, a&#160;correlation between a deeper angle of insertion (AID) and better hearing was reported12,13. In most EAS patients, the residual hearing gradually deteriorates over time14. Identifying the responsible gene for HL allows&#160;one to predict future hearing. When it is anticipated that their hearing would be lost across all frequencies in the future, EAS with longer electrodes, not shorter electrodes, is&#160;ideal in providing&#160;a higher percentage of cochlear coverage15. The optimal AID was thought to range from 630&#176; to 720&#176;16,17,18, corresponding to the distribution of spiral ganglion neurons in the human cochlea. However, as each cochlear duct length (CDL) has a wide range of variation19, measuring the CDL in each case was required to achieve the appropriate AID, even in EAS patients. Recently, commercially available software (see Table of Materials) allowed the measurment&#160;of each CDL easily based on computed tomography (CT) data, which was clinically feasible.
This protocol describes the following: (1) a preoperative evaluation that included genetic analysis to identify the etiology of HL and cochlear duct length measurement to determine the optimal electrode length, (2) a less invasive surgical procedure via exoscopy and endoscopy, and (3) the postoperative hearing outcome and mapping strategy in patients with high-frequency HL who underwent EAS with a longer electrode.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>DEXART 3.3 mg</td>
			<td>Fuji Pharma</td>
			<td>22100AMX01404</td>
			<td>equal to dexamethasone sodium phosphate (4 mg)</td>
		</tr>
		<tr>
			<td>DEXART 6.6 mg</td>
			<td>Fuji Pharma</td>
			<td>22100AMX01402</td>
			<td>equal to dexamethasone sodium phosphate (8 mg)</td>
		</tr>
		<tr>
			<td>Fentanyl injection 0.1 mg</td>
			<td>TERUMO</td>
			<td>22100AMX00009</td>
			<td></td>
		</tr>
		<tr>
			<td>MAESTRO 7.0</td>
			<td>MED-EL</td>
			<td>4582290238456</td>
			<td>fitting software for map settings</td>
		</tr>
		<tr>
			<td>Midas Rex MR8&#160;</td>
			<td>Medtronic</td>
			<td>301ADBZX00046000</td>
			<td>high speed drill</td>
		</tr>
		<tr>
			<td>OTOPLAN software</td>
			<td>Cascination / MED-EL</td>
			<td>REF 20125</td>
			<td>for measuring cochlear duct length (CDL)&#160;</td>
		</tr>
		<tr>
			<td>Predonine tablets</td>
			<td>Shionogi</td>
			<td>16000AMZ01740000</td>
			<td></td>
		</tr>
		<tr>
			<td>Propofol 1% 50 mL</td>
			<td>Maruishi Pharmaceutical Co.,Ltd</td>
			<td>30100AMX00158</td>
			<td></td>
		</tr>
		<tr>
			<td>Remifentanil 2 mg</td>
			<td>Daiichi-Sankyo</td>
			<td>22800AMX00090</td>
			<td></td>
		</tr>
		<tr>
			<td>Rocuronium bromide 50 mg/50 mL</td>
			<td>Maruishi Pharmaceutical Co.,Ltd</td>
			<td>22800AMX00534</td>
			<td></td>
		</tr>
		<tr>
			<td>SONNET2 EAS</td>
			<td>MED-EL</td>
			<td>4582290241807</td>
			<td>processor</td>
		</tr>
		<tr>
			<td>Synchrony2 FLEX28</td>
			<td>MED-EL</td>
			<td>4571573943026</td>
			<td>cochlear implant (electrode)</td>
		</tr>
		<tr>
			<td>Xylocaine 0.5% with epinephrine</td>
			<td>Sandoz Pharma</td>
			<td>4KUZ13127</td>
			<td></td>
		</tr>
	</tbody>
</table>

enhanced cochlear coverage and hearing preservation in high-frequency hearing loss via electric acoustic stimulation with longer electrode

Electric-acoustic stimulation (EAS) is a promising treatment to improve hearing ability in patients with high-frequency hearing loss (HL). In EAS surgeries, shorter electrodes have been preferred to avoid the presence of an electrode covering the residual hearing region. However, our earlier studies showed that EAS with longer electrodes (28 mm) could preserve acoustic hearing. Additionally, we reported that the hearing preservation (HP) scores were independent of the length of the inserted electrodes, consistent with the systematic review. As most EAS patients gradually lose residual hearing over time due to the natural course of HL, in these cases, providing broader cochlear coverage using longer electrodes was beneficial toward better place-pitch matching. In addition to preparing for the deterioration in&#160;hearing in&#160;the future, EAS with longer electrodes could offer various types of map strategies. Herein, we show the pre-, intra-, and post-procedures for EAS surgery. Appropriate preoperative evaluation, less invasive surgery, flexible lateral-wall electrodes, and steroid administration resulted in good HP following EAS with longer electrodes.

EAS was conducted on 10 patients (11 ears) who fulfilled the audiological criteria for EAS (refer to Table 1). The inclusion criteria comprised the following: bilateral pure-tone hearing levels &#8804;65 dBHL for 125 Hz, 250 Hz, and 500 Hz; &#8805;80 dBHL at 2000 Hz; and &#8805;85 dBHL at 4000 Hz and 8000 Hz. Additionally, minimal benefit from conventional hearing aids was required, defined as monosyllable scores in quiet below 60% even in the optimal aided condition. All participants underwent EAS using longer electrodes (see Table of Materials). Figure 1 shows the preoperative and 6-month postoperative audiograms following EAS surgery, suggesting that residual low-frequency hearing was well-preserved in all cases. According to the hearing preservation (HP) classification system reported by Skarzynski et al.20, 36.4% (4 of 11 cases) showed complete HP, and 63.6% (7 of 11 cases) showed partial HP. There were no cases of significant hearing deterioration.
Case presentation (Case #8) 
At the age of 5, during a routine elementary school wellness check-up, a 14-year-old girl who had not undergone newborn hearing screening was flagged for suspected hearing loss (HL). Subsequently diagnosed with high-frequency HL, she began using hearing aids. Given the observed deterioration in her hearing, she sought evaluation at our department at the age of 13.
Pathogenic variants of the CDH23 gene were identified via genetic testing6. Since the residual hearing was likely to deteriorate&#160;due to CDH23-related HL, a longer electrode was selected to cover the acoustic region. She underwent EAS surgery on the left ear at the age of 14. The residual hearing was completely preserved 6 months after surgery. She preferred &#34;electric-stimulation (ES)-only mapping&#34; with activated apical electrodes traversing the region of residual hearing at that time (Figure 2). The patient was satisfied with the acoustic amplification obtained using ES at low frequencies.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/66565/66565fig01.jpg" /> 
Figure 1: Average air-conduction hearing thresholds. The dashed and solid lines indicate preoperative and 6-month postoperative measurements, respectively. Gray and black lines show the individual data and the mean, respectively. This figure has been adapted from Yoshimura et al.6. <a href="https://www.jove.com/files/ftp_upload/66565/66565fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/66565/66565fig02.jpg" /> 
Figure 2: Clinical findings of Case #8. (A) Pedigree of the patient. (B) Preoperative and 6-month postoperative audiograms. Electrode array illustrations represent insertion depth. (C) Postoperative X-ray findings, with numbers corresponding to individual channels. (D) Imaging for each electrode location and the reference tonotopic map. This figure has been adapted from Yoshimura et al.6. <a href="https://www.jove.com/files/ftp_upload/66565/66565fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/66565/66565fig03.jpg" /> 
Figure 3: Three types of mapping strategy in patients with EAS using longer electrodes. (A) EAS (Overlap/OFF) map. Some of the apical contacts were deactivated, while the acoustic stimulation (AS) was activated. (B) EAS (Overlap/ON) map. Both electrical stimulation (ES) in the cochlear implantation (CI) default setting and AS were utilized. (C) ES-only map. In the ES setting, the frequency range was set from 70-8,500 Hz. AS was deactivated. <a href="https://www.jove.com/files/ftp_upload/66565/66565fig03large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Patient&#160;</td>
			<td></td>
			<td>Implanted&#160;</td>
			<td>Implanted&#160;</td>
			<td>Responsible</td>
			<td>Pre-op</td>
			<td>6M post-op</td>
			<td>HP numerical</td>
			<td>HP</td>
		</tr>
		<tr>
			<td>No.</td>
			<td>Gender</td>
			<td>age (years)</td>
			<td>side</td>
			<td>Gene</td>
			<td>LFA (dB)</td>
			<td>LFA (dB)</td>
			<td>scale (%)</td>
			<td>classification</td>
		</tr>
		<tr>
			<td>1</td>
			<td>F</td>
			<td>12</td>
			<td>L</td>
			<td>SLC26A4</td>
			<td>63.3</td>
			<td>70</td>
			<td>70.8</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td>2</td>
			<td>F</td>
			<td>9</td>
			<td>L</td>
			<td>SLC26A4</td>
			<td>50</td>
			<td>65</td>
			<td>62.5</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td>3</td>
			<td>M</td>
			<td>50</td>
			<td>L</td>
			<td>CDH23</td>
			<td>50</td>
			<td>56.7</td>
			<td>78.6</td>
			<td>Complete</td>
		</tr>
		<tr>
			<td>4</td>
			<td>F</td>
			<td>31</td>
			<td>L</td>
			<td>Unknown</td>
			<td>45</td>
			<td>61.7</td>
			<td>67.7</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td>31</td>
			<td>R</td>
			<td></td>
			<td>46.7</td>
			<td>56.7</td>
			<td>75.9</td>
			<td>Complete</td>
		</tr>
		<tr>
			<td>5</td>
			<td>F</td>
			<td>57</td>
			<td>R</td>
			<td>Unknown</td>
			<td>38.3</td>
			<td>65</td>
			<td>59</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td>6</td>
			<td>F</td>
			<td>55</td>
			<td>R</td>
			<td>Unknown</td>
			<td>26.7</td>
			<td>55</td>
			<td>68.4</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td>7</td>
			<td>M</td>
			<td>21</td>
			<td>R</td>
			<td>LOXHD1</td>
			<td>33.3</td>
			<td>66.7</td>
			<td>37.2</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td>8</td>
			<td>F</td>
			<td>14</td>
			<td>R</td>
			<td>CDH23</td>
			<td>56.7</td>
			<td>48.3</td>
			<td>100</td>
			<td>Complete</td>
		</tr>
		<tr>
			<td>9</td>
			<td>M</td>
			<td>20</td>
			<td>L</td>
			<td>Unknown</td>
			<td>51.7</td>
			<td>73.3</td>
			<td>48.1</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td>10</td>
			<td>M</td>
			<td>64</td>
			<td>R</td>
			<td>Unknown</td>
			<td>51.7</td>
			<td>58.3</td>
			<td>82.1</td>
			<td>Complete</td>
		</tr>
	</tbody>
</table>
Table 1: Summary of subject characteristics and hearing preservation outcomes. This table has been adapted from Yoshimura et al.6.

Author Spotlight: Optimizing EAS with Long Electrodes for Enhanced Cochlear Coverage and Hearing Preservation

Electric acoustic stimulation (EAS) with longer electrodes can offer broader cochlear coverage and various types of maps in cases of high-frequency hearing loss. Combining less invasive surgery, flexible lateral-wall electrodes, and steroid administration permits deeper insertion with little or no surgical trauma, resulting in good preservation of hearing.

Enhanced Cochlear Coverage and Hearing Preservation in High-Frequency Hearing Loss via Electric Acoustic Stimulation with Longer Electrode

Electric-acoustic stimulation (EAS) is a promising treatment to improve hearing ability in patients with high-frequency hearing loss (HL). In EAS ...

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654 Views.  Shinshu University School of Medicine. Electric acoustic stimulation (EAS) with longer electrodes can offer broader cochlear coverage and various types of maps in cases of high-frequency hearing loss. Combining less invasive surgery, flexible lateral-wall electrodes, and steroid administration permits deeper insertion with little or no surgical trauma, resulting in good preservation of hearing.

Video: Author Spotlight: Optimizing EAS with Long Electrodes for Enhanced Cochlear Coverage and Hearing Preservation

Permanent Cerebral Vessel Occlusion via Double Ligature and Transection

Stroke is a leading cause of death, disability, and socioeconomic loss worldwide. The majority of all strokes result from an interruption in blood flow (ischemia) 1. Middle cerebral artery (MCA) delivers a great majority of blood to the lateral surface of the cortex 2, is the most common site of human stroke 3, and ischemia within its territory can result in extensive dysfunction or death 1,4,5. Survivors of ischemic stroke often suffer loss or disruption of motor capabilities, sensory deficits, and infarct. In an effort to capture these key characteristics of stroke, and thereby develop effective treatment, a great deal of emphasis is placed upon animal models of ischemia in MCA.
Here we present a method of permanently occluding a cortical surface blood vessel. We will present this method using an example of a relevant vessel occlusion that models the most common type, location, and outcome of human stroke, permanent middle cerebral artery occlusion (pMCAO). In this model, we surgically expose MCA in the adult rat and subsequently occlude via double ligature and transection of the vessel. This pMCAO blocks the proximal cortical branch of MCA, causing ischemia in all of MCA cortical territory, a large portion of the cortex. This method of occlusion can also be used to occlude more distal portions of cortical vessels in order to achieve more focal ischemia targeting a smaller region of cortex. The primary disadvantages of pMCAO are that the surgical procedure is somewhat invasive as a small craniotomy is required to access MCA, though this results in minimal tissue damage. The primary advantages of this model, however, are: the site of occlusion is well defined, the degree of blood flow reduction is consistent, functional and neurological impairment occurs rapidly, infarct size is consistent, and the high rate of survival allows for long-term chronic assessment.

Permanent Cerebral Vessel Occlusion via Double Ligature and Transection

We describe a highly reproducible method for the permanent occlusion of a rodent major cerebral blood vessel. This technique can be accomplished with very little peripheral damage, minimal blood loss, a high rate of long-term survival, and consistent infarct volume commensurate with the human clinical population.

Stroke is a leading cause of death, disability, and socioeconomic loss worldwide. The majority of all strokes result from an interruption in blood flow ...

Interictal High Frequency Oscillations Detected with Simultaneous Magnetoencephalography and Electroencephalography as Biomarker of Pediatric Epilepsy

Crucial to the success of epilepsy surgery is the availability of a robust biomarker that identifies the Epileptogenic Zone (EZ). High Frequency Oscillations (HFOs) have emerged as potential presurgical biomarkers for the identification of the EZ in addition to Interictal Epileptiform Discharges (IEDs) and ictal activity. Although they are promising to localize the EZ, they are not yet suited for the diagnosis or monitoring of epilepsy in clinical practice. Primary barriers remain: the lack of a formal and global definition for HFOs; the consequent heterogeneity of methodological approaches used for their study; and the practical difficulties to detect and localize them noninvasively from scalp recordings. Here, we present a methodology for the recording, detection, and localization of interictal HFOs from pediatric patients with refractory epilepsy. We report representative data of HFOs detected noninvasively from interictal scalp EEG and MEG from two children undergoing surgery.
The underlying generators of HFOs were localized by solving the inverse problem and their localization was compared to the Seizure Onset Zone (SOZ) as this was defined by the epileptologists. For both patients, Interictal Epileptogenic Discharges (IEDs) and HFOs were localized with source imaging at concordant locations. For one patient, intracranial EEG (iEEG) data were also available. For this patient, we found that the HFOs localization was concordant between noninvasive and invasive methods. The comparison of iEEG with the results from scalp recordings served to validate these findings. To our best knowledge, this is the first study that presents the source localization of scalp HFOs from simultaneous EEG and MEG recordings comparing the results with invasive recordings. These findings suggest that HFOs can be reliably detected and localized noninvasively with scalp EEG and MEG. We conclude that the noninvasive localization of interictal HFOs could significantly improve the presurgical evaluation for pediatric patients with epilepsy.

High Frequency Oscillations (HFOs) have emerged as presurgical biomarkers for the identification of the epileptogenic zone in pediatric patients with medically refractory epilepsy. A methodology for the noninvasive recording, detection, and localization of HFOs with simultaneous scalp electroencephalography (EEG) and magnetoencephalography (MEG) is presented.

Crucial to the success of epilepsy surgery is the availability of a robust biomarker that identifies the Epileptogenic Zone (EZ). High Frequency ...

Neonatal Murine Cochlear Explant Technique as an In Vitro Screening Tool in Hearing Research

While there have been remarkable advances in hearing research over the past few decades, there is still no cure for Sensorineural Hearing Loss (SNHL), a condition that typically involves damage to or loss of the delicate mechanosensory structures of the inner ear. Sophisticated in vitro and ex vivo assays have emerged in recent years, enabling the screening of an increasing number of potentially therapeutic compounds while minimizing resources and accelerating efforts to develop cures for SNHL. Though homogenous cultures of certain cell types continue to play an important role in current research, many scientists now rely on more complex organotypic cultures of murine inner ears, also known as cochlear explants. The preservation of organized cellular structures within the inner ear facilitates the in situ evaluation of various components of the cochlear infrastructure, including inner and outer hair cells, spiral ganglion neurons, neurites, and supporting cells. Here we present the preparation, culture, treatment, and immunostaining of neonatal murine cochlear explants. The careful preparation of these explants facilitates the identification of mechanisms that contribute to SNHL and constitutes a valuable tool for the hearing research community.

Neonatal Murine Cochlear Explant Technique as an In Vitro Screening Tool in Hearing Research

The goal of this protocol is to demonstrate the preparation, culture, treatment, and immunostaining of neonatal murine cochlear explants. The technique can be utilized as an in vitro screening tool in hearing research.

While there have been remarkable advances in hearing research over the past few decades, there is still no cure for Sensorineural Hearing Loss (SNHL), a ...

In Vivo Morphometric Analysis of Human Cranial Nerves Using Magnetic Resonance Imaging in Meni&#232;re's Disease Ears and Normal Hearing Ears

Analysis of neural structures in Meni&#232;re's Disease (MD) is of importance, since a loss of such structures has previously been proposed for this patient group but has yet to be confirmed. This protocol describes a method of in vivo evaluation of neural changes especially well suitable for cranial nerve analysis using magnetic resonance imaging (MRI). MD-patients and normal hearing persons were examined in a 3-T MR-scanner using a scan protocol including strongly T2-weighted 3D gradient-echo-sequence (3D-CISS). In the patient group, MD was additionally confirmed using MRI-based assessment of endolymphatic hydrops. Morphometric analysis was performed using a freeware DICOM viewer. Evaluation of cranial nerves included measurements of cross-sectional areas (CSAs) of the nerves at different levels as well as orthogonal diametric measurements.

To evaluate morphological changes of cranial nerves such as loss of neural structures or swelling of cranial nerves in Meni&#232;re&#39;s Disease (MD) or in healthy persons in vivo, a protocol of evaluation has been developed using magnetic resonance imaging (MRI). Additional MRI-based confirmation of MD was performed.

Analysis of neural structures in Meni&#232;re's Disease (MD) is of importance, since a loss of such structures has previously been proposed for this ...

Measurement of Strial Blood Flow in Mouse Cochlea Utilizing an Open Vessel-Window and Intravital Fluorescence Microscopy

Transduction of sound is metabolically demanding, and the normal function of the microvasculature in the lateral wall is critical for maintaining endocochlear potential, ion transport, and fluid balance. Different forms of hearing disorders are reported to involve abnormal microcirculation in the cochlea. Investigation of how cochlear blood flow (CoBF) pathology affects hearing function is challenging due to the lack of feasible interrogation methods and the difficulty in accessing the inner ear. An open vessel-window in the lateral cochlear wall, combined with fluorescence intravital microscopy, has been used for studying CoBF changes in vivo, but mostly in guinea pig and only recently in the mouse. This paper and the associated video describe the open vessel-window method for visualizing blood flow in the mouse cochlea. Details include 1) preparation of the fluorescent-labeled blood cell suspension from mice; 2) construction of an open vessel-window for intravital microscopy in an anesthetized mouse, and 3) measurement of blood flow velocity and volume using an offline recording of the imaging. The method is presented in video format to show how to use the open window approach in mouse to investigate structural and functional changes in the cochlear microcirculation under normal and pathological conditions.

An open vessel-window approach using fluorescent tracers provides sufficient resolution for cochlear blood flow (CoBF) measurement. The method facilitates the study of structural and functional changes in CoBF in mouse under normal and pathological conditions.

Transduction of sound is metabolically demanding, and the normal function of the microvasculature in the lateral wall is critical for maintaining ...

In vitro Time-lapse Live-Cell Imaging to Explore Cell Migration toward the Organ of Corti

To study the effects of mesenchymal stem cells (MSCs) on cell regeneration and treatment, this method tracks MSC migration and morphological changes after co-culture with cochlear epithelium. The organ of Corti was immobilized on a plastic coverslip by pressing a portion of the Reissner's membrane generated during the dissection. MSCs confined by a glass cylinder migrated toward cochlear epithelium when the cylinder was removed. Their predominant localization was observed in the modiolus of the organ of Corti, aligned in a direction similarly to that of the nerve fibers. However, some MSCs were localized in the limbus area and showed a horizontally elongated shape. In addition, migration into the hair cell area was increased, and the morphology of the MSCs changed to various forms after kanamycin treatment. In conclusion, the results of this study indicate that the coculture of MSCs with cochlear epithelium will be useful for the development of therapeutics via cell transplantation and for studies of cell regeneration that can examine various conditions and factors.

In this study, we present a real-time imaging method using confocal microscopy to observe cells moving toward damaged tissue by ex vivo incubation with the cochlear epithelium containing the organ of Corti.

To study the effects of mesenchymal stem cells (MSCs) on cell regeneration and treatment, this method tracks MSC migration and morphological changes after ...

Fertility Preservation in Patients with Severe Ovarian Dysfunction

Ovarian function progressively declines during aging and in some pathophysiological conditions including karyotype abnormality, autoimmune diseases, chemo- and radiation-therapies, as well as ovarian surgeries. In unmarried women with severe ovarian dysfunction, fertility preservation is important for future pregnancies. Although oocyte cryopreservation is an established method for fertility preservation, these patients could only preserve a limited number of oocytes even after ovarian hyperstimulation, leading to repeated stimulations to ensure sufficient oocytes to guarantee future pregnancy. To solve this issue, we have recently developed a drug-free in vitro activation (IVA) procedure, which enable us to stimulate early stages of ovarian follicles to develop to the preantral follicle stage. These preantral follicles can respond to the unique protocol of gonadotropin stimulation, resulting in increased number of retrieved oocytes per ovarian stimulation for cryopreservation. The drug-free IVA comprised from the surgical approach and ovarian stimulation. We removed a part of cortex from one or both ovaries from patients under laparoscopic surgery. The ovarian cortical tissues were cut into small cubes to disrupt the Hippo signaling pathway and stimulate the development of early stage follicles. These cubes were grafted orthotropically into remaining ovaries as well as beneath the serosa of both Fallopian tubes. We have already published the surgical procedure of the drug-free IVA and the protocol of subsequent ovarian stimulation, but herein we present the details of laboratory methods required for drug-free IVA.

We present details of laboratory procedures for drug-free in vitro activation (IVA) of ovarian follicles for patients with severe ovarian dysfunction. This method could increase the number of retrievable oocytes per ovarian hyperstimulation and benefit fertility preservation for those patients.

Ovarian function progressively declines during aging and in some pathophysiological conditions including karyotype abnormality, autoimmune diseases, ...

Endaural Endoscopic Atticoantrotomy (Retrograde Mastoidectomy) using a Constant Suction Bone-drilling Technique

Endoscopic middle ear surgery is a widely employed minimally invasive surgical technique to address middle ear and mastoid pathology. Bone drilling is the main technical challenge of endoscopic middle ear surgery. The accompanying video describes the detailed protocol of a constant-suction bone-drilling technique and the procedure of endaural exclusive endoscopic atticoantrotomy (retrograde mastoidectomy) using this technique. The main components of this bone-drilling technique include a soft and flexible suction tube, which is placed into the tympanic cavity to provide constant suction, and a soft sleeve, which is wrapped around the drill shaft to prevent the high-speed rotating shaft from damaging the lens of the endoscope. With these simple modifications, the traditional otological electrodrill can be used for drilling a tiny endaural incision in endoscopic middle ear surgery. Based on this bone-drilling technique, endaural endoscopic atticoantrotomy (retrograde mastoidectomy) can be successfully established for the removal of various amounts of bone, depending on the extent of the lesion. The short-term postoperative outcome seems promising.

Endaural Endoscopic Atticoantrotomy Retrograde Mastoidectomy using a Constant Suction Bone-drilling Technique

In this paper, we present the protocol and short-term outcomes of endaural exclusive endoscopic atticoantrotomy using a constant suction bone-drilling technique.

Endoscopic middle ear surgery is a widely employed minimally invasive surgical technique to address middle ear and mastoid pathology. Bone drilling is the ...

Performing Intracochlear Electrocochleography During Cochlear Implantation

Electrocochleography (ECochG) measures inner ear potentials generated in response to acoustic stimulation of the ear. These potentials reflect the residual function of the cochlea. In cochlear implant candidates with residual hearing, the implant electrode can directly measure ECochG responses during the implantation process. Various authors have described the ability to monitor the inner ear function by continuous ECochG measurements during the surgery. The measurement of ECochG signals during surgery is not trivial. There are no interpretable signals in up to 20% of cases. For a successful recording, a standardized procedure is recommended to achieve the highest measurement reliability and avoid possible pitfalls. Therefore, seamless collaboration between the CI surgeon and CI technician is key. This video consists of an overview of the system setup and a stepwise procedure of performing intracochlear ECochG measurements during CI surgery. It shows the surgeon's and the CI technician's roles in the process, and how a smooth collaboration between the two is made possible.

Electrocochleography (ECochG) measures inner ear potentials generated in response to acoustic stimulation. In cochlear implant (CI) candidates, such inner ear potentials can be measured directly with the implant electrodes. In this video, we systematically explain how to perform ECochG recordings during CI surgery.

Electrocochleography (ECochG) measures inner ear potentials generated in response to acoustic stimulation of the ear. These potentials reflect the ...

Robotic Cochlear Implantation for Direct Cochlear Access

Robot-assisted systems offer great potential for gentler and more precise cochlear implantation. In this article, we provide a comprehensive overview of the clinical workflow for robotic cochlear implantation using a robotic system specifically developed for a minimally invasive, direct cochlear access. The clinical workflow involves experts from various disciplines and requires training to ensure a smooth and safe procedure. The protocol briefly summarizes the history of robotic cochlear implantation. The clinical sequence is explained in detail, beginning with the assessment of patient eligibility and covering surgical preparation, preoperative planning with the special planning software, drilling of the middle ear access, intraoperative imaging to confirm the trajectory, milling of the inner ear access, insertion of the electrode array, and implant management. The steps that require special attention are discussed. As an example, the postoperative outcome of robotic cochlear implantation in a patient with advanced otosclerosis is presented. Finally, the procedure is discussed in the context of the authors' experience.

Robotic cochlear implantation is a procedure for minimally invasive inner ear access. Compared to conventional surgery, robotic cochlear implantation involves additional steps that need to be carried out in the operating room. In this article we give a description of the procedure and highlight the important aspects of robotic cochlear implantation.

Robot-assisted systems offer great potential for gentler and more precise cochlear implantation. In this article, we provide a comprehensive overview of ...