Original Research—Laryngology and Neurolaryngology
Laryngeal Reinnervation Featuring Refined Nerve-Muscle Pedicle Implantation Evaluated via Electromyography and Use of Coronal Images
Otolaryngology– Head and Neck Surgery 2015, Vol. 152(4) 697–705 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599815568945 http://otojournal.org
Tetsuji Sanuki, MD, PhD1, Eiji Yumoto, MD, PhD1, Kohei Nishimoto, MD, PhD1, Narihiro Kodama1, Haruka Kodama, MD1, and Ryosei Minoda, MD, PhD1
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Abstract Objective. To evaluate the long-term efficacy of laryngeal reinnervation via refined nerve-muscle pedicle (NMP) flap implantation combined with arytenoid adduction to treat unilateral vocal fold paralysis (UVFP), employing laryngeal electromyography (LEMG), coronal imaging, and phonatory function assessment. Study Design. Case series with chart review. Setting. University hospital. Subjects and Methods. We retrospectively reviewed 12 UVFP patients who underwent refined NMP implantation with arytenoid adduction. Videostroboscopy, phonatory functional analysis, LEMG, and coronal imaging were performed before and 2 years after surgery. In LEMG analysis, a 4-point scale was employed to grade motor unit (MU) recruitment: 41 reflected no recruitment, 31 greatly decreased recruitment, 21 moderately decreased recruitment, and 11 mildly decreased activity, associated with less than the full interference pattern. Coronal images were assessed in terms of differences in thickness and the vertical positions of the vocal folds. Results. Phonatory function improved significantly after operation in all patients. In terms of LEMG findings, the preoperative MU recruitment scores were 11 in no patients, 21 in 4 patients, 31 in 1 patient, and 41 in 7 patients. Postoperative MU recruitment results were 11 in 6 patients, 21 in 5 patients, 31 in 1 patient, and 41 in no patients. Thinning of the affected fold during phonation was evident preoperatively in 9 of 10 patients. The affected and healthy folds were equal in volume in 4 of 9 patients postoperatively. Conclusion. The LEMG findings and coronal imaging suggest that NMP implantation may have enabled successful reinnervation of the laryngeal muscles of UVFP patients.
Keywords unilateral vocal fold paralysis, laryngeal reinnervation, nervemuscle pedicle implantation, laryngeal electromyography, coronal reconstructed image Received August 22, 2014; revised December 22, 2014; accepted January 2, 2015.
T
he causes of unilateral vocal fold paralysis (UVFP) are commonly iatrogenic, neoplastic, idiopathic, and traumatic.1,2 UVFP is characterized by varying degrees of hoarseness, a weak cough, and occasional aspiration, all of which impair patient quality of life. Surgical management of UVFP has concerned researchers for decades, but a completely satisfactory treatment has remained elusive. Management options include vocal fold injection,3 type I thyroplasty,4 arytenoid adduction (AA),5 and laryngeal reinnervation.6 Although voice quality may improve upon vocal fold injection, type I thyroplasty, and AA, static surgical procedures such as these cannot prevent muscle atrophy.7 Laryngeal reinnervation has been shown to be effective when used to counter muscle atrophy caused by denervation and to improve both the bulk and the positioning of the vocal folds.8-10 Our understanding of the physiological responses to reinnervation in humans is limited, because the histological correlates derived in work on animal reinnervation are lacking.
1
Department of Otolaryngology–Head & Neck Surgery, Graduate School of Medicine, Kumamoto University, Kumamoto, Japan This article was presented at the 2014 AAO-HNSF Annual Meeting & OTO EXPO; September 21-24, 2014; Orlando, Florida. Corresponding Author: Tetsuji Sanuki, MD, PhD, Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. Email: [email protected]
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Furthermore, animal models do not accurately predict human reinnervation outcomes, as reestablishment of movement does not occur in human larynges. To restore the tone of immobile vocal folds, Tucker11 carried out nerve-muscle pedicle (NMP) flap implantation into the thyroarytenoid (TA) muscle via a window created in the thyroid ala. May and Beery12 reported that NMP implantation into the lateral cricothyroid muscle yielded positive outcomes in patients with breathy dysphonia. However, to the best of our knowledge, no studies except those noted above have explored the utilities of NMP flaps further. We earlier explored the outcomes of NMP flap implementation in rats and confirmed that the approach was effective when used to reverse or repair atrophic changes in TA muscles that had been denervated for a long time.13,14 We refined the technique of NMP flap implantation onto the TA muscle and have applied this innovative method, in combination with AA, to treat patients with breathy dysphonia caused by UVFP, commencing in July 2002.15,16 Laryngeal electromyography (LEMG) is useful for assessing the nature and extent of neurogenic pathology involving acute vocal fold paralysis and for evaluating the prognosis of recurrent laryngeal nerve (RLN) functional recovery.9,17 However, LEMG evaluation during phonation of UVFP patients who had undergone refined NMP implantation combined with AA has not been previously performed. Such work should clarify the innervation status of the TA muscle. Videostroboscopy is the standard means used to evaluate the vocal folds of patients with UVFP. However, supraglottal constriction, including overadduction of the ventricular fold, anterior-to-posterior shortening of the glottis, and anterior tilting of the arytenoid portion, may prevent visualization of the vocal folds in some UVFP patients, such that videostroboscopy cannot be used to assess differences in the vertical positions and thicknesses of these folds.18 We earlier developed a 3-dimensional computed tomography (3DCT) technique using reconstructed coronal images to measure the thicknesses of, and to determine the locations of, the vocal folds, during both phonation and inhalation; this identifies glottal configuration.18-21 In this study, we used LEMG, glottal configuration, videostroboscopic findings, and vocal function assessment to evaluate patients before and after refined NMP flap implantation with AA, carried out to treat UVFP.
Materials and Methods Patient Characteristics This study was approved by the Institutional Review Board of Kumamoto University Hospital. The charts of all patients who underwent refined NMP flap implantation with AA from July 2002 to January 2012 were reviewed. The diagnosis was confirmed based on patient history and clinical examination using fiber-optic nasopharyngoscopy and videostroboscopy. In all patients, the examination revealed a wide glottal gap and complete paralysis. We included UVFP patients who underwent at
least 2 years of follow-up and who were studied via videostroboscopy, acoustic analysis, perceptual evaluation, aerodynamic analysis, examination of coronal reconstructed images, and LEMG both pre- and postoperatively.
Operative Procedure Refined NMP flap implantation with AA was performed under general anesthesia. The technique has been described previously15,16 but was refined as follows: first, the NMP flap was harvested from the sternohyoid (SH) muscle. During surgery, an electrical stimulator was used to confirm the functionality of the ansa cervicalis (AC). AA was then performed according to the method of Isshiki et al.5 Microscopic control was used in creating the thyroid cartilage window and in precise placement of the NMP flap onto the TA muscle. To affix the NMP flap onto the TA muscle, no less than 2 sutures with 9-0 nylon were used.
Videostroboscopy Video recordings were randomized. Stroboscopic images (Pulsar 20140020; Karl-Stroz, Tokyo, Japan) obtained during sustained phonation of the vowels /e/ or /i/, using either a rigid oblique-view endoscope (SFT-1; Nagashima, Tokyo, Japan) or a videoendoscope (VNL-1171K; Pentax, Tokyo, Japan), depending on patient tolerance, were recorded on a digital videocassette (DVCPRO; Panasonic, Yokohama, Japan) to assess glottal closure patterns. Glottal closure (0 = none, 1 = slight, 2 = one-third gap between both vocal folds, 3 = two-thirds gap, 4 = an open glottis during phonation), regularity of vocal fold vibration (0 = normal, 1 = mildly abnormal, 2 = moderately abnormal), and amplitude (0 = normal, 1 = reduced, 2 = absent) were assessed based on analysis of video images obtained upon observation of the static larynx and during speech. Our grading of videostroboscopic data using an ordinal scale has been previously described.22 Two trained laryngologists (T.S., E.Y.) and 1 speech pathologist (N.K.), all blinded to patient data, evaluated each recording using this scale. Their scores were averaged.
Vocal Function Assessment Vocal function assessment included perceptual evaluation, acoustic analysis, and measurement of maximum phonation time (MPT) and mean flow rate (MFR). When measuring MPT, the patient was instructed to produce sustained phonation of the vowel /a/ for as long as possible, at a comfortable pitch and loudness. MPT was measured twice for each patient using a stopwatch, and the higher value was recorded. MFR was measured using a phonatory function analyzer (PS-77E; Nagashima). The patient was instructed to produce the /a/ vowel at a comfortable pitch and loudness. Pre- and postoperative voice samples containing the sustained vowels /a/ and /e/, and associated speech samples, were subjected to both perceptual evaluation and acoustic analysis.16 Three authors (T.S., E.Y., and N.K.) performed voice assessments using a perceptual rating scale (GRBAS) measuring voice quality and characteristics. All
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ratings were conducted in a blinded fashion; patient voice samples were randomly presented. The perceptual scale used allowed each listener to rate voice quality on a scale (0 = normal, 1 = mildly poor, 2 = moderately poor, 3 = severely affected) using each of the parameters mentioned above. The ratings of the 3 listeners were averaged. Acoustic parameters associated with enunciation of a sustained vowel /a/ sound were evaluated using the MultiDimensional Voice Program model 5105 (version 3.1.7; Kay Elemetrics, Lincoln Park, New Jersey). The acoustic parameters evaluated included the harmonics-to-noise ratio (HNR), jitter, and shimmer. 21
Laryngeal Electromyography
We obtained monopolar EMG traces using a measuring system (MEB-9200; NihonKohden, Tokyo, Japan) in which the filter settings lay between 20 Hz and 10 kHz. Motor unit (MU) recruitment traces of both vocal folds were recorded. A second channel featured a microphone time locked to the EMG signal. With the patient’s neck extended, monopolar fine-wire platinum electrodes were percutaneously placed through 23-gauge needles into the TA and lateral cricothyroid (LCA) muscle complex. A 4-point scale was used to grade MU recruitment: 41 represented no recruitment, 31 greatly decreased recruitment, 21 moderately decreased recruitment, and 11 mildly decreased activity (an interference pattern that was less than complete). Our method of grading MU recruitment, using the original scale of Munin, has been previously reported.21,23
CT Scanning and Evaluation of Glottal Configuration CT was used to obtain coronal multiplanar reconstructed images. The methodology has been reported elsewhere.18,20,21 Briefly, the subjects lay in a supine position with a pillow under the neck. Scans were performed with a 64-row multislice helical CT scanner (Lightspeed VCT; GE Healthcare, Chalfont, St Giles, UK) at 200 mA, 120 kV, with a slice thickness of 0.625 mm and a table speed of 53.7 mm/s. Each subject was instructed to sustain the vowel /a/ at a low volume and to inhale slowly for 5 seconds. The subjects practiced prior to scanning. Then, each subject was scanned during sustained phonation and, subsequently, during slow inhalation. Coronal 1- or 2-mm-thick images perpendicular to the glottic axis were systematically built in all subjects. Two authors (T.S. and E.Y.) evaluated coronal images in a blinded manner. The images were displayed on a monitor and analyzed in terms of differences in the thicknesses and vertical positions of the vocal folds during phonation. To maintain consistency among the coronal images of all patients, vocal fold measurements were made at the point anterior to the vocal process. The images were also examined in terms of the differences in thicknesses and horizontal positions of the affected vocal folds between active phonation and subsequent inhalation and compared with images of healthy vocal folds. When a disagreement was apparent, the judges examined the images together until a consensus was attained.
Statistical Analysis Significant differences between pre- and postoperative videostroboscopic data, perceptual evaluation scores, acoustic analyses, MPT and MFR results, and EMG findings were analyzed using Wilcoxon’s signed-rank test. Significant differences between pre- and postoperative glottal configuration data were analyzed using the McNemar test. All statistical analyses were performed using StatView 5.0 for Windows (SAS Institute, Cary, North Carolina). A P value less than .05 was considered to be statistically significant.
Results In total, 51 UVFP patients with severe paralytic dysphonia underwent refined NMP flap implantation combined with AA between July 2002 and January 2012 at Kumamoto University Hospital. We excluded UVFP patients lost to follow-up (n = 6). A minimum of 6 months was allowed to elapse after the time of onset of paralysis to allow possible spontaneous reinnervation or compensation without a need for surgery. Thirty-three patients underwent preoperative LEMG. Fourteen patients who underwent refined NMP flap implantation combined with AA underwent LEMG in the 2year interval after surgery. Two of the 14 patients did not receive preoperative LEMG. Consequently, 12 patients were enrolled (5 men, 7 women; age range, 37-74 years, median 60.6 years) in the present study (Table 1). The median duration of UVFP prior to surgery was 12.0 months (range, 6-59 months).The follow-up period ranged from 24 to 45 months (median, 32.0 months). Subjective and objective voice parameters were evaluated pre- and postoperatively (at 24 months). In some cases, patients did not undergo videostroboscopic examination, vocal function testing, or CT.
Videostroboscopic Findings Preoperative videostroboscopy showed that most cases presented with mildly to severely bowed vocal fold edges, severely incomplete glottal closure, and very irregular vocal fold vibration during phonation (Figure 1A). Two years after surgery, videostroboscopy revealed straight vocal fold edges, midline vocal fold positioning, symmetrical and regular vocal fold vibration, and complete glottal closure during phonation (Figure 1B). No contradictory motion of the affected vocal fold was observed postoperatively, and glottal closure (0.3 6 0.5), regularity (0.2 6 0.4), and the amplitude of vocal fold vibration (0.2 6 0.3) were significantly improved compared with the preoperative values (3.4 6 0.8, 1.5 6 0.6, and 1.8 6 0.9, P = .0050, .0067, and .0048, respectively; Table 2).
Aerodynamic Studies The postoperative MPT and MFR values (17.5 6 6.8 seconds, 168.1 6 54.1 mL/s) were significantly better than the preoperative values (4.3 6 1.8 seconds, 769.7 6 626.5 mL/s, P = .0022, .0047, respectively; Table 3).
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Table 1. Patient Demographics and Perceptual Analysis.
Patient
Gender Age, y
1 2
F M
70 71
3
F
37
4
F
51
5
M
48
6
M
58
7
F
66
8
M
74
9
F
57
10
M
63
11 12
F F
66 66
Average P value
Cause Thyroid surgery Aortic aneurysms surgery Thyroid surgery Skull base surgery Thyroid surgery Thyroid surgery Thyroid surgery Aortic Aneurysms surgery Thyroid surgery Thyroid surgery Lung surgery Thyroid surgery
60.6
Overall Grade Roughness Breathiness Asthenia Strain Interval, Follow-up, Side mo mo Preop Postop Preop Postop Preop Postop Preop Postop Preop Postop R L
13 11
45 25
3.0 3.0
0.7 0.3
0.3 0.0
0.3 0.0
3.0 3.0
0.3 0.3
0.7 1.3
0.3 0.0
1.0 0.0
0.0 0.0
L
21
24
2.0
0.3
0.0
0.0
2.0
0.3
0.7
0.3
0.0
0.0
R
7
33
1.7
0.0
0.0
0.0
1.7
0.0
1.0
0.0
0.0
0.0
L
18
40
NA
0.0
NA
0.0
NA
0.0
NA
0.0
NA
0.0
L
7
28
2.0
0.0
0.0
0.0
2.0
0.0
0.3
0.0
0.0
0.0
L
14
33
3.0
0.7
0.3
0.0
3.0
0.7
0.7
0.0
0.0
0.0
L
9
35
3.0
0.0
0.0
0.0
3.0
0.0
2.0
0.0
0.0
0.0
L
59
28
1.0
0.0
0.0
0.0
1.0
0.0
0.3
0.0
0.0
0.0
L
6
29
2.7
0.0
0.0
0.0
2.7
0.0
0.0
0.0
0.0
0.0
R R
6 35
36 28
2.7 3.0
0.0 0.3
0.3 0.0
0.0 0.0
2.0 3.0
0.0 0.3
0.7 0.3
0.0 0.0
0.3 0.0
0.0 0.0
12.0
32.0
2.5 0.2 .0032
0.1 0.0 .2417
2.4 0.2 .0000
0.7 0.1 .0002
0.1 0.0 .1310
Abbreviation: NA, not assessed.
Figure 1. Videostroboscopic findings (patient 2). Preoperatively, there is severely incomplete glottic closure (A). Postoperatively, the bulk of left fold appears to be identical to that of right fold (B). X indicates the affected side. Downloaded from oto.sagepub.com at WEST VIRGINA UNIV on April 17, 2015
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Table 2. Videostroboscopic Findings. Glottal Closure
Regularity
Amplitude
Patient
Preop
Postop
Preop
Postop
Preop
Postop
1 2 3 4 5 6 7 8 9 10 11 12 Average P value
NA 2.0 3.3 4.0 3.8 2.0 4.0 4.0 3.0 4.0 3.3 3.7 3.4
0.0 0.0 0.0 0.5 0.5 0.3 1.0 0.0 0.3 0.0 1.3 NA 0.3
NA 2.0 0.8 1.0 2.0 0.3 2.0 2.0 1.0 2.0 1.5 2.0 1.5
0.0 0.0 0.0 0.0 0.0 0.3 0.0 0.0 0.8 0.0 1.0 NA 0.2
NA 4.0 1.3 1.0 2.0 0.8 2.0 2.0 1.0 2.0 1.8 2.0 1.8
0.3 0.0 0.0 0.0 0.0 0.3 0.0 0.0 0.5 0.0 1.0 NA 0.2
.0050
.0067
.0048
Abbreviation: NA, not assessed.
Table 3. Aerodynamic and Acoustic Analysis. MPT, s
MFR, mL/s
Jitter, %
Shimmer, dB
HNR, Hz
Patient
Preop
Postop
Preop
Postop
Preop
Postop
Preop
Postop
Preop
Postop
1 2 3 4 5 6 7 8 9 10 11 12 Average P value
2.9 3 6.3 6.3 3.5 4.8 2.8 1.6 6.8 2.7 6.7 4.3 4.3
17.2 11 13.3 12.0 21.8 14.8 27.1 18.3 11.6 11.3 32.5 19.6 17.5
2000 2000 398 223 731 480 420 960 170 960 394 500 769.7
109 158 141 238 223 233 172 174 200 198 87 84 168.1
12.17 NA 4.11 6.33 NA 5.55 9.62 NA 4.72 12.96 3.90 10.28 7.74
0.74 0.96 0.47 1.97 0.50 0.85 1.49 0.43 0.45 0.56 0.67 1.61 0.89
22.3 NA 4.6 11.5 NA 8.9 11.9 NA 10.1 13.3 9.3 15.9 12.0
2.9 6.2 3.4 7.1 4.0 8.6 6.7 5.2 3.7 4.6 3.1 5.8 5.1
0.8 NA 7.5 5.7 NA 9.0 2.3 NA 8.2 2.2 5.4 3.3 4.9
8.8 7.9 9.2 7.7 9.0 7.5 7.8 8.6 9.4 9.2 8.6 9.3 8.6
.0022
.0047
.0077
.0077
.0152
Abbreviations: HNR, harmonics-to-noise ratio; MFR, mean flow rate; MPT, maximum phonation time; NA, not assessed.
Perceptual Evaluation and Acoustic Analysis
Laryngeal Electromyographic Findings
Table 1 shows that the overall grade awarded upon perceptual evaluation of dysphonia severity improved significantly postoperatively, as did breathiness and asthenia (P = .0032, .0000, and .0002, respectively). In Table 3, postoperative jitter and shimmer values (0.89% 6 0.5%, 5.1 6 1.8 dB) upon UVFP were significantly lower than the preoperative values (7.74% 6 3.5%, 12.0 6 5.0 dB, P = .0077, .0077), and the postoperative HNR values (8.6 6 0.7 Hz) were significantly higher than the preoperative values (4.9 6 2.9 Hz, P = .0152).
Denervation patterns evident during the EMG response were identified by reference to 1 or 2 MU action potentials (MUPs), or fibrillation potentials, at multiple sites of the muscle tested (patient 9). This pattern is evident when muscle fibers that are not under neuronal control fire spontaneously. The pre- and postoperative LEMG findings are shown in Table 2. Before surgery, 41 or 31 MU recruitment was noted in 8 patients. Other patients (patients 4, 7, 8, and 11) exhibited 21 MU recruitment during phonation. The vocal
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Table 4. Electromyographic and Glottal Configuration Findings. MU Recruitment Pt 1 2 3 4 5 6 7 8 9 10 11 12 P value
Thickness of Vocal Fold
Vertical Position of Vocal Fold
Preop
Postop
Preop
Postop
Preop
Postop
41 41 41 21 31 41 21 21 41 41 21 41
11 11 11 21 21 11 21 21 21 31 11 11
P P P P P NA NA P P = P P
P NA NA = P = P NA P = = P
= PS = = PS NA NA = = PS = PS
= NA NA = = = = NA = = = PS
.0065
.1740
.0580
Abbreivations: =, equal; MU, motor unit; NA, not assessed; P, paralyzed side, atrophic in comparison to unaffected side; PS, paralyzed side in superior position to unaffected side.
function of such patients was as poor as that of patients with 41 or 31 MU recruitment (Table 4). At 24 months following surgery, we again performed EMG testing. The results showed activation of the TA muscle along with improved vocal function in all patients who underwent the refined NMP implantation procedure (Table 4; Figure 2). One patient (patient 10) exhibited 31 MU recruitment 24 months after surgery, and the vocal function entered the near-normal range. Of the 12 patients (patient 4, 7, 8, and 11) who exhibited 21 MU recruitment before surgery, 4 had almost the same recruitment values 24 months after surgery. LEMG revealed significant postoperative improvements in voluntary MU recruitment, compared with preoperative MU recruitment during phonation (P = .0065; Table 4).
Evaluation of Glottal Configuration Based on Coronal Images During phonation, the vocal folds on the affected sides of 9 (90%) of 10 subjects before surgery were thinner than those on the healthy sides. Before surgery, the affected vocal fold was higher than the healthy fold during phonation in 4 subjects (40%). After surgery, the thickness of the affected fold in 4 (44.4%) of 9 patients was equal to that of the fold on the normal side during phonation (P = .174; Table 4). In 8 of 9 subjects (88.9%), the affected vocal fold was located at the same level as the healthy fold during phonation (P = .058; Table 4). Figure 3 shows the affected fold of patient 8 located at the same level as the healthy fold, which was thinner than the paralyzed fold before surgery (Figure 3A, B). Postoperatively, the affected fold attained the same thickness as the healthy fold during phonation (Figure 3C, D).
Discussion Laryngeal reinnervation affords the laryngologist another tool aiding vocal rehabilitation after UVFP. Although Tucker11 and May and Beery12 reported on the effectiveness of NMP flap implantation in treating breathy dysphonia due to UVFP, this procedure did not subsequently gain wide use. Previously, we reported that refined NMP flap implantation with AA, when used to treat UVFP, afforded excellent vocal function after surgery.15,16 In this refined technique, the NMP flap is harvested from the SH muscle, whereas Tucker11,24 and May and Beery12 raised the NMP flap from the omohyoid (OH) muscle. The AC branch to the SH muscle is thicker than that to the OH muscle and hence contains a larger number of regenerating axons. During surgery, an electrical stimulator was used to confirm the functionality of the AC. In addition, a cartilage window was made, and precise placement of the NMP flap onto the TA muscle was undertaken under microscopic control. In our present series of patients, perceptual and acoustic analyses, MPT, and MFR showed that they developed nearnormal ranges of vocal function over 24 months after surgery. Postoperative videostroboscopy revealed that patients treated with this procedure achieved complete glottal closure, with regular and even amplitudes on both sides of the vocal fold during phonation. Apposition of the symmetrical structures observed on videostroboscopy allowed the 2 vocal folds to oscillate both synchronously and symmetrically, thus reducing aperiodicity and perturbation and resulting in the production of a normally perceived tone. This was associated with significant improvements in postoperative perceptual evaluations (grade, breathiness, and asthenia) and acoustic data (jitter, shimmer, and HNR). Turning to voluntary MU recruitment in the TA/LCA muscle complex of the affected vocal fold during phonation, 7 cases lacked MUP, 5 exhibited mixed-type interference,
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Figure 2. Laryngeal electromyographic findings of a representative patient (patient 12). Recruitment of the affected fold exhibited no interference preoperatively. Postoperative recruitment of the reinnervated fold was associated with full interference.
Figure 3. Coronal reconstruction images (patient 8). The affected fold is thinner (thin arrow). At 24 months after surgery, the affected fold is the same thickness as the unaffected fold (thick arrow).
and no case presented with full interference preoperatively. This suggests that reinnervation of laryngeal muscles occurred in most UVFP patients over time after the onset of UVFP. This represents so-called ‘‘subclinical reinnervation.’’ If such reinnervation does not adequately restore neuronal function to the laryngeal muscles, the affected vocal fold remains paralyzed. However, subclinical reinnervation may help to prevent laryngeal muscle atrophy to some extent. In addition, some studies have found that the laryngeal muscle may retain an ability to receive regenerating nerve axons, even after long-term denervation.25,26 Such findings support the feasibility of delayed laryngeal reinnervation to treat UVFP. Patient 10 exhibited greatly decreased recruitment (31) 24 months
after surgery, with vocal fold function in the near-normal range. In an attempt to explain this result, there is a possibility that the AA procedure was successful despite a failure in the NMP flap implantation. This would result in improved vocal outcome with a seemingly paradoxical decreased recruitment value. Alternatively, there also exists the possibility that the monopolar electrode did not detect the TA muscle reinnervation area of the NMP flap implantation. It should be noted that were this the case, there might be limitations in the use of EMG electrodes in the measurement of MU recruitment. We previously assessed laryngeal muscle activity in UVFP patients using LEMG, aerodynamic analysis, and evaluation of glottal configuration via 3DCT.21 It was shown that MU recruitment affected the vertical position of the damaged fold during phonation. In the present study, before surgery, the vocal folds on the affected sides in 9 of 10 patients were thinner than those on the healthy sides during phonation. After surgery, the thickness of affected folds in 4 of 9 patients was equal to that of the fold on the normal side during phonation. This suggests that application of the refined NMP flap implantation improves TA/LCA muscle tone during phonation. In terms of vertical position, in 8 of 9 patients (88.9%), the affected fold attained a position, postoperatively, equal to that of the healthy fold. In 4 of the 8 patients (50%), the thickness of the affected folds was equal to that of the folds on the healthy side. Thus, reinnervation of the TA muscle by refined NMP flap implantation and AA was successful when used to equalize the vertical positions of the 2 folds. In the present work, LEMG revealed a significant increase, postoperatively, in the density of MU potentials in the TA/ LCA muscle complex during phonation. Postoperative EMG showed that the affected laryngeal muscles were successfully reinnervated via refined NMP flap implantation and that the TA/LCA muscle complex was activated by phonation. Preoperative LEMG showed that half of our patients may have
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maintained partial RLN innervation; NMP flap implantation into such TA/LCA muscle complexes either did not affect, or improved, postoperative recruitment compared to the preoperative levels during phonation and afforded excellent postoperative vocal function. Aoyama et al27 found that NMP flap implantation efficiently reduced atrophic changes developing in TA muscles retaining partial RLN innervation in an animal model. Thus, NMP flap implantation may also be useful in the treatment of patients in whom partial innervation (subclinical reinnervation) of the TA muscle is suspected.
Conclusion In this study, the LEMG findings and coronal imaging suggested that NMP flap implantation enabled successful reinnervation of the laryngeal muscles of UVFP patients. Thus, refined NMP flap implantation with AA is an effective surgical combination for the treatment of the severe dysphonia associated with UVFP. Author Contributions Tetsuji Sanuki, design, data analysis, drafting and revising the manuscript, final approval of the version to be published; Eiji Yumoto, data analysis and revising the manuscript, final approval of the version to be published; Kohei Nishimoto, data acquisition of LEMG and coronal images and interpretation of data, revising the manuscript; Narihiro Kodama, data analysis of phonatory function and videostroboscopy, revising the manuscript; Haruka Kodama, data acquisition of LEMG and coronal images and interpretation of data, revising the manuscript; Ryosei Minoda, contribution to making the manuscript and interpretation of data.
Disclosures Competing interests: None. Sponsorships: None. Funding source: This work was supported by JSPS KAKENHI Grant Number 25293349.
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7. Benninger MS, Crumley RL, Ford CN, et al. Evaluation and treatment of the unilateral paralyzed vocal fold. Otolaryngol Head Neck Surg. 1994;111:497-508. 8. Lee WT, Milstein C, Hicks D, Akst LM, Esclamado RM. Results of ansa to recurrent laryngeal nerve reinnervation. Otolaryngol Head Neck Surg. 2007;136:450-454. 9. Zheng H, Li Z, Zhou S, Cuan Y, Wen W. Update: laryngeal reinnervation for unilateral vocal cord paralysis with the ansa cervicalis. Laryngoscope. 1996;106:1522-1527. 10. Crumley RL. Update: ansa cervicalis to recurrent laryngeal nerve anastomosis for unilateral laryngeal paralysis. Laryngoscope. 1991;101:384-387. 11. Tucker HM. Reinnervation of the unilaterally paralyzed larynx. Ann Otol Rhinol Laryngol. 1977;86:789-794. 12. May M, Beery Q. Muscle-nerve pedicle laryngeal reinnervation. Laryngoscope. 1986;96:1196-1200. 13. Kumai Y, Ito T, Udaka N, Yumoto E. Effects of a nervemuscle pedicle on the denervated rat thyroarytenoid muscle. Laryngoscope. 2006;116:1027-1032. 14. Miyamaru S, Kumai Y, Ito T, Sanuki T, Yumoto E. Nervemuscle pedicle implantation facilitates re-innervation of longterm denervated thyroarytenoid muscle in rats. Acta Otolaryngol. 2009;129:1486-1492. 15. Yumoto E, Sanuki T, Toya Y, Kodama N, Kumai Y. Nervemuscle pedicle flap implantation combined with arytenoid adduction. Arch Otolaryngol Head Neck Surg. 2010;136:965969. 16. Hassan MM, Yumoto E, Baraka MA, Sanuki T, Kodama N. Arytenoid rotation and nerve-muscle pedicle transfer in paralytic dysphonia. Laryngoscope. 2011;121:1018-1022. 17. Maronian N, Waugh P, Robinson L, Hillel A. Electromyographic findings in recurrent laryngeal nerve reinnervation. Ann Otol Rhinol Laryngol. 2003;112:314-323. 18. Yumoto E, Sanuki T, Minoda R, Kumai Y, Nishimoto K. Glottal configuration in unilaterally paralyzed larynx and vocal function. Acta Otolaryngol. 2013;133:187-193. 19. Yumoto E, Nakano K, Oyamada Y. Relationship between 3D behavior of the unilaterally paralyzed larynx and aerodynamic vocal function. Acta Otolaryngol. 2003;123:274-278. 20. Yumoto E, Oyamada Y, Nakano K, Nakayama Y, Yamashita Y. Three-dimensional characteristics of the larynx with immobile vocal fold. Arch Otolaryngol Head Neck Surg. 2004;130: 967-974. 21. Sanuki T, Yumoto E, Nishimoto K, Minoda R. Laryngeal muscle activity in unilateral vocal fold paralysis patients using electromyography and coronal reconstructed images. Otolaryngol Head Neck Surg. 2014;150:625-630. 22. Yumoto E, Sanuki T, Kumai Y. Immediate recurrent laryngeal nerve reconstruction and vocal outcome. Laryngoscope. 2006; 116:1657-1661. 23. Munin MC, Rosen CA, Zullo T. Utility of laryngeal electromyography in predicting recovery after vocal fold paralysis. Arch Phys Med Rehabil. 2003;84:1150-1153. 24. Tucker HM. Combined surgical medialization and nervemuscle pedicle reinnervation for unilateral vocal fold paralysis: improved functional results and prevention of long-term deterioration of voice. J Voice. 1997;11:474-478.
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25. Miyamaru S, Kumai Y, Ito T, Yumoto E. Effects of long-term denervation on the rat thyroarytenoid muscle. Laryngoscope. 2008;118:1318-1323. 26. Kano S, Horowitz JB, Sasaki CT. Posterior cricoarytenoid muscle denervation. Arch Otolaryngol Head Neck Surg. 1991; 117:1019-1020.
27. Aoyama T, Kumai Y, Yumoto E, Ito T, Miyamaru S. Effects of nerve-muscle pedicle on immobile rat vocal folds in the presence of partial innervation. Ann Otol Rhinol Laryngol. 2010;119:823-829.
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Laryngeal Reinnervation Featuring Refined Nerve-Muscle Pedicle Implantation Evaluated via Electromyography and Use of Coronal Images
Otolaryngology– Head and Neck Surgery 2015, Vol. 152(4) 697–705 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599815568945 http://otojournal.org
Tetsuji Sanuki, MD, PhD1, Eiji Yumoto, MD, PhD1, Kohei Nishimoto, MD, PhD1, Narihiro Kodama1, Haruka Kodama, MD1, and Ryosei Minoda, MD, PhD1
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Abstract Objective. To evaluate the long-term efficacy of laryngeal reinnervation via refined nerve-muscle pedicle (NMP) flap implantation combined with arytenoid adduction to treat unilateral vocal fold paralysis (UVFP), employing laryngeal electromyography (LEMG), coronal imaging, and phonatory function assessment. Study Design. Case series with chart review. Setting. University hospital. Subjects and Methods. We retrospectively reviewed 12 UVFP patients who underwent refined NMP implantation with arytenoid adduction. Videostroboscopy, phonatory functional analysis, LEMG, and coronal imaging were performed before and 2 years after surgery. In LEMG analysis, a 4-point scale was employed to grade motor unit (MU) recruitment: 41 reflected no recruitment, 31 greatly decreased recruitment, 21 moderately decreased recruitment, and 11 mildly decreased activity, associated with less than the full interference pattern. Coronal images were assessed in terms of differences in thickness and the vertical positions of the vocal folds. Results. Phonatory function improved significantly after operation in all patients. In terms of LEMG findings, the preoperative MU recruitment scores were 11 in no patients, 21 in 4 patients, 31 in 1 patient, and 41 in 7 patients. Postoperative MU recruitment results were 11 in 6 patients, 21 in 5 patients, 31 in 1 patient, and 41 in no patients. Thinning of the affected fold during phonation was evident preoperatively in 9 of 10 patients. The affected and healthy folds were equal in volume in 4 of 9 patients postoperatively. Conclusion. The LEMG findings and coronal imaging suggest that NMP implantation may have enabled successful reinnervation of the laryngeal muscles of UVFP patients.
Keywords unilateral vocal fold paralysis, laryngeal reinnervation, nervemuscle pedicle implantation, laryngeal electromyography, coronal reconstructed image Received August 22, 2014; revised December 22, 2014; accepted January 2, 2015.
T
he causes of unilateral vocal fold paralysis (UVFP) are commonly iatrogenic, neoplastic, idiopathic, and traumatic.1,2 UVFP is characterized by varying degrees of hoarseness, a weak cough, and occasional aspiration, all of which impair patient quality of life. Surgical management of UVFP has concerned researchers for decades, but a completely satisfactory treatment has remained elusive. Management options include vocal fold injection,3 type I thyroplasty,4 arytenoid adduction (AA),5 and laryngeal reinnervation.6 Although voice quality may improve upon vocal fold injection, type I thyroplasty, and AA, static surgical procedures such as these cannot prevent muscle atrophy.7 Laryngeal reinnervation has been shown to be effective when used to counter muscle atrophy caused by denervation and to improve both the bulk and the positioning of the vocal folds.8-10 Our understanding of the physiological responses to reinnervation in humans is limited, because the histological correlates derived in work on animal reinnervation are lacking.
1
Department of Otolaryngology–Head & Neck Surgery, Graduate School of Medicine, Kumamoto University, Kumamoto, Japan This article was presented at the 2014 AAO-HNSF Annual Meeting & OTO EXPO; September 21-24, 2014; Orlando, Florida. Corresponding Author: Tetsuji Sanuki, MD, PhD, Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. Email: [email protected]
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Furthermore, animal models do not accurately predict human reinnervation outcomes, as reestablishment of movement does not occur in human larynges. To restore the tone of immobile vocal folds, Tucker11 carried out nerve-muscle pedicle (NMP) flap implantation into the thyroarytenoid (TA) muscle via a window created in the thyroid ala. May and Beery12 reported that NMP implantation into the lateral cricothyroid muscle yielded positive outcomes in patients with breathy dysphonia. However, to the best of our knowledge, no studies except those noted above have explored the utilities of NMP flaps further. We earlier explored the outcomes of NMP flap implementation in rats and confirmed that the approach was effective when used to reverse or repair atrophic changes in TA muscles that had been denervated for a long time.13,14 We refined the technique of NMP flap implantation onto the TA muscle and have applied this innovative method, in combination with AA, to treat patients with breathy dysphonia caused by UVFP, commencing in July 2002.15,16 Laryngeal electromyography (LEMG) is useful for assessing the nature and extent of neurogenic pathology involving acute vocal fold paralysis and for evaluating the prognosis of recurrent laryngeal nerve (RLN) functional recovery.9,17 However, LEMG evaluation during phonation of UVFP patients who had undergone refined NMP implantation combined with AA has not been previously performed. Such work should clarify the innervation status of the TA muscle. Videostroboscopy is the standard means used to evaluate the vocal folds of patients with UVFP. However, supraglottal constriction, including overadduction of the ventricular fold, anterior-to-posterior shortening of the glottis, and anterior tilting of the arytenoid portion, may prevent visualization of the vocal folds in some UVFP patients, such that videostroboscopy cannot be used to assess differences in the vertical positions and thicknesses of these folds.18 We earlier developed a 3-dimensional computed tomography (3DCT) technique using reconstructed coronal images to measure the thicknesses of, and to determine the locations of, the vocal folds, during both phonation and inhalation; this identifies glottal configuration.18-21 In this study, we used LEMG, glottal configuration, videostroboscopic findings, and vocal function assessment to evaluate patients before and after refined NMP flap implantation with AA, carried out to treat UVFP.
Materials and Methods Patient Characteristics This study was approved by the Institutional Review Board of Kumamoto University Hospital. The charts of all patients who underwent refined NMP flap implantation with AA from July 2002 to January 2012 were reviewed. The diagnosis was confirmed based on patient history and clinical examination using fiber-optic nasopharyngoscopy and videostroboscopy. In all patients, the examination revealed a wide glottal gap and complete paralysis. We included UVFP patients who underwent at
least 2 years of follow-up and who were studied via videostroboscopy, acoustic analysis, perceptual evaluation, aerodynamic analysis, examination of coronal reconstructed images, and LEMG both pre- and postoperatively.
Operative Procedure Refined NMP flap implantation with AA was performed under general anesthesia. The technique has been described previously15,16 but was refined as follows: first, the NMP flap was harvested from the sternohyoid (SH) muscle. During surgery, an electrical stimulator was used to confirm the functionality of the ansa cervicalis (AC). AA was then performed according to the method of Isshiki et al.5 Microscopic control was used in creating the thyroid cartilage window and in precise placement of the NMP flap onto the TA muscle. To affix the NMP flap onto the TA muscle, no less than 2 sutures with 9-0 nylon were used.
Videostroboscopy Video recordings were randomized. Stroboscopic images (Pulsar 20140020; Karl-Stroz, Tokyo, Japan) obtained during sustained phonation of the vowels /e/ or /i/, using either a rigid oblique-view endoscope (SFT-1; Nagashima, Tokyo, Japan) or a videoendoscope (VNL-1171K; Pentax, Tokyo, Japan), depending on patient tolerance, were recorded on a digital videocassette (DVCPRO; Panasonic, Yokohama, Japan) to assess glottal closure patterns. Glottal closure (0 = none, 1 = slight, 2 = one-third gap between both vocal folds, 3 = two-thirds gap, 4 = an open glottis during phonation), regularity of vocal fold vibration (0 = normal, 1 = mildly abnormal, 2 = moderately abnormal), and amplitude (0 = normal, 1 = reduced, 2 = absent) were assessed based on analysis of video images obtained upon observation of the static larynx and during speech. Our grading of videostroboscopic data using an ordinal scale has been previously described.22 Two trained laryngologists (T.S., E.Y.) and 1 speech pathologist (N.K.), all blinded to patient data, evaluated each recording using this scale. Their scores were averaged.
Vocal Function Assessment Vocal function assessment included perceptual evaluation, acoustic analysis, and measurement of maximum phonation time (MPT) and mean flow rate (MFR). When measuring MPT, the patient was instructed to produce sustained phonation of the vowel /a/ for as long as possible, at a comfortable pitch and loudness. MPT was measured twice for each patient using a stopwatch, and the higher value was recorded. MFR was measured using a phonatory function analyzer (PS-77E; Nagashima). The patient was instructed to produce the /a/ vowel at a comfortable pitch and loudness. Pre- and postoperative voice samples containing the sustained vowels /a/ and /e/, and associated speech samples, were subjected to both perceptual evaluation and acoustic analysis.16 Three authors (T.S., E.Y., and N.K.) performed voice assessments using a perceptual rating scale (GRBAS) measuring voice quality and characteristics. All
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ratings were conducted in a blinded fashion; patient voice samples were randomly presented. The perceptual scale used allowed each listener to rate voice quality on a scale (0 = normal, 1 = mildly poor, 2 = moderately poor, 3 = severely affected) using each of the parameters mentioned above. The ratings of the 3 listeners were averaged. Acoustic parameters associated with enunciation of a sustained vowel /a/ sound were evaluated using the MultiDimensional Voice Program model 5105 (version 3.1.7; Kay Elemetrics, Lincoln Park, New Jersey). The acoustic parameters evaluated included the harmonics-to-noise ratio (HNR), jitter, and shimmer. 21
Laryngeal Electromyography
We obtained monopolar EMG traces using a measuring system (MEB-9200; NihonKohden, Tokyo, Japan) in which the filter settings lay between 20 Hz and 10 kHz. Motor unit (MU) recruitment traces of both vocal folds were recorded. A second channel featured a microphone time locked to the EMG signal. With the patient’s neck extended, monopolar fine-wire platinum electrodes were percutaneously placed through 23-gauge needles into the TA and lateral cricothyroid (LCA) muscle complex. A 4-point scale was used to grade MU recruitment: 41 represented no recruitment, 31 greatly decreased recruitment, 21 moderately decreased recruitment, and 11 mildly decreased activity (an interference pattern that was less than complete). Our method of grading MU recruitment, using the original scale of Munin, has been previously reported.21,23
CT Scanning and Evaluation of Glottal Configuration CT was used to obtain coronal multiplanar reconstructed images. The methodology has been reported elsewhere.18,20,21 Briefly, the subjects lay in a supine position with a pillow under the neck. Scans were performed with a 64-row multislice helical CT scanner (Lightspeed VCT; GE Healthcare, Chalfont, St Giles, UK) at 200 mA, 120 kV, with a slice thickness of 0.625 mm and a table speed of 53.7 mm/s. Each subject was instructed to sustain the vowel /a/ at a low volume and to inhale slowly for 5 seconds. The subjects practiced prior to scanning. Then, each subject was scanned during sustained phonation and, subsequently, during slow inhalation. Coronal 1- or 2-mm-thick images perpendicular to the glottic axis were systematically built in all subjects. Two authors (T.S. and E.Y.) evaluated coronal images in a blinded manner. The images were displayed on a monitor and analyzed in terms of differences in the thicknesses and vertical positions of the vocal folds during phonation. To maintain consistency among the coronal images of all patients, vocal fold measurements were made at the point anterior to the vocal process. The images were also examined in terms of the differences in thicknesses and horizontal positions of the affected vocal folds between active phonation and subsequent inhalation and compared with images of healthy vocal folds. When a disagreement was apparent, the judges examined the images together until a consensus was attained.
Statistical Analysis Significant differences between pre- and postoperative videostroboscopic data, perceptual evaluation scores, acoustic analyses, MPT and MFR results, and EMG findings were analyzed using Wilcoxon’s signed-rank test. Significant differences between pre- and postoperative glottal configuration data were analyzed using the McNemar test. All statistical analyses were performed using StatView 5.0 for Windows (SAS Institute, Cary, North Carolina). A P value less than .05 was considered to be statistically significant.
Results In total, 51 UVFP patients with severe paralytic dysphonia underwent refined NMP flap implantation combined with AA between July 2002 and January 2012 at Kumamoto University Hospital. We excluded UVFP patients lost to follow-up (n = 6). A minimum of 6 months was allowed to elapse after the time of onset of paralysis to allow possible spontaneous reinnervation or compensation without a need for surgery. Thirty-three patients underwent preoperative LEMG. Fourteen patients who underwent refined NMP flap implantation combined with AA underwent LEMG in the 2year interval after surgery. Two of the 14 patients did not receive preoperative LEMG. Consequently, 12 patients were enrolled (5 men, 7 women; age range, 37-74 years, median 60.6 years) in the present study (Table 1). The median duration of UVFP prior to surgery was 12.0 months (range, 6-59 months).The follow-up period ranged from 24 to 45 months (median, 32.0 months). Subjective and objective voice parameters were evaluated pre- and postoperatively (at 24 months). In some cases, patients did not undergo videostroboscopic examination, vocal function testing, or CT.
Videostroboscopic Findings Preoperative videostroboscopy showed that most cases presented with mildly to severely bowed vocal fold edges, severely incomplete glottal closure, and very irregular vocal fold vibration during phonation (Figure 1A). Two years after surgery, videostroboscopy revealed straight vocal fold edges, midline vocal fold positioning, symmetrical and regular vocal fold vibration, and complete glottal closure during phonation (Figure 1B). No contradictory motion of the affected vocal fold was observed postoperatively, and glottal closure (0.3 6 0.5), regularity (0.2 6 0.4), and the amplitude of vocal fold vibration (0.2 6 0.3) were significantly improved compared with the preoperative values (3.4 6 0.8, 1.5 6 0.6, and 1.8 6 0.9, P = .0050, .0067, and .0048, respectively; Table 2).
Aerodynamic Studies The postoperative MPT and MFR values (17.5 6 6.8 seconds, 168.1 6 54.1 mL/s) were significantly better than the preoperative values (4.3 6 1.8 seconds, 769.7 6 626.5 mL/s, P = .0022, .0047, respectively; Table 3).
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Table 1. Patient Demographics and Perceptual Analysis.
Patient
Gender Age, y
1 2
F M
70 71
3
F
37
4
F
51
5
M
48
6
M
58
7
F
66
8
M
74
9
F
57
10
M
63
11 12
F F
66 66
Average P value
Cause Thyroid surgery Aortic aneurysms surgery Thyroid surgery Skull base surgery Thyroid surgery Thyroid surgery Thyroid surgery Aortic Aneurysms surgery Thyroid surgery Thyroid surgery Lung surgery Thyroid surgery
60.6
Overall Grade Roughness Breathiness Asthenia Strain Interval, Follow-up, Side mo mo Preop Postop Preop Postop Preop Postop Preop Postop Preop Postop R L
13 11
45 25
3.0 3.0
0.7 0.3
0.3 0.0
0.3 0.0
3.0 3.0
0.3 0.3
0.7 1.3
0.3 0.0
1.0 0.0
0.0 0.0
L
21
24
2.0
0.3
0.0
0.0
2.0
0.3
0.7
0.3
0.0
0.0
R
7
33
1.7
0.0
0.0
0.0
1.7
0.0
1.0
0.0
0.0
0.0
L
18
40
NA
0.0
NA
0.0
NA
0.0
NA
0.0
NA
0.0
L
7
28
2.0
0.0
0.0
0.0
2.0
0.0
0.3
0.0
0.0
0.0
L
14
33
3.0
0.7
0.3
0.0
3.0
0.7
0.7
0.0
0.0
0.0
L
9
35
3.0
0.0
0.0
0.0
3.0
0.0
2.0
0.0
0.0
0.0
L
59
28
1.0
0.0
0.0
0.0
1.0
0.0
0.3
0.0
0.0
0.0
L
6
29
2.7
0.0
0.0
0.0
2.7
0.0
0.0
0.0
0.0
0.0
R R
6 35
36 28
2.7 3.0
0.0 0.3
0.3 0.0
0.0 0.0
2.0 3.0
0.0 0.3
0.7 0.3
0.0 0.0
0.3 0.0
0.0 0.0
12.0
32.0
2.5 0.2 .0032
0.1 0.0 .2417
2.4 0.2 .0000
0.7 0.1 .0002
0.1 0.0 .1310
Abbreviation: NA, not assessed.
Figure 1. Videostroboscopic findings (patient 2). Preoperatively, there is severely incomplete glottic closure (A). Postoperatively, the bulk of left fold appears to be identical to that of right fold (B). X indicates the affected side. Downloaded from oto.sagepub.com at WEST VIRGINA UNIV on April 17, 2015
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Table 2. Videostroboscopic Findings. Glottal Closure
Regularity
Amplitude
Patient
Preop
Postop
Preop
Postop
Preop
Postop
1 2 3 4 5 6 7 8 9 10 11 12 Average P value
NA 2.0 3.3 4.0 3.8 2.0 4.0 4.0 3.0 4.0 3.3 3.7 3.4
0.0 0.0 0.0 0.5 0.5 0.3 1.0 0.0 0.3 0.0 1.3 NA 0.3
NA 2.0 0.8 1.0 2.0 0.3 2.0 2.0 1.0 2.0 1.5 2.0 1.5
0.0 0.0 0.0 0.0 0.0 0.3 0.0 0.0 0.8 0.0 1.0 NA 0.2
NA 4.0 1.3 1.0 2.0 0.8 2.0 2.0 1.0 2.0 1.8 2.0 1.8
0.3 0.0 0.0 0.0 0.0 0.3 0.0 0.0 0.5 0.0 1.0 NA 0.2
.0050
.0067
.0048
Abbreviation: NA, not assessed.
Table 3. Aerodynamic and Acoustic Analysis. MPT, s
MFR, mL/s
Jitter, %
Shimmer, dB
HNR, Hz
Patient
Preop
Postop
Preop
Postop
Preop
Postop
Preop
Postop
Preop
Postop
1 2 3 4 5 6 7 8 9 10 11 12 Average P value
2.9 3 6.3 6.3 3.5 4.8 2.8 1.6 6.8 2.7 6.7 4.3 4.3
17.2 11 13.3 12.0 21.8 14.8 27.1 18.3 11.6 11.3 32.5 19.6 17.5
2000 2000 398 223 731 480 420 960 170 960 394 500 769.7
109 158 141 238 223 233 172 174 200 198 87 84 168.1
12.17 NA 4.11 6.33 NA 5.55 9.62 NA 4.72 12.96 3.90 10.28 7.74
0.74 0.96 0.47 1.97 0.50 0.85 1.49 0.43 0.45 0.56 0.67 1.61 0.89
22.3 NA 4.6 11.5 NA 8.9 11.9 NA 10.1 13.3 9.3 15.9 12.0
2.9 6.2 3.4 7.1 4.0 8.6 6.7 5.2 3.7 4.6 3.1 5.8 5.1
0.8 NA 7.5 5.7 NA 9.0 2.3 NA 8.2 2.2 5.4 3.3 4.9
8.8 7.9 9.2 7.7 9.0 7.5 7.8 8.6 9.4 9.2 8.6 9.3 8.6
.0022
.0047
.0077
.0077
.0152
Abbreviations: HNR, harmonics-to-noise ratio; MFR, mean flow rate; MPT, maximum phonation time; NA, not assessed.
Perceptual Evaluation and Acoustic Analysis
Laryngeal Electromyographic Findings
Table 1 shows that the overall grade awarded upon perceptual evaluation of dysphonia severity improved significantly postoperatively, as did breathiness and asthenia (P = .0032, .0000, and .0002, respectively). In Table 3, postoperative jitter and shimmer values (0.89% 6 0.5%, 5.1 6 1.8 dB) upon UVFP were significantly lower than the preoperative values (7.74% 6 3.5%, 12.0 6 5.0 dB, P = .0077, .0077), and the postoperative HNR values (8.6 6 0.7 Hz) were significantly higher than the preoperative values (4.9 6 2.9 Hz, P = .0152).
Denervation patterns evident during the EMG response were identified by reference to 1 or 2 MU action potentials (MUPs), or fibrillation potentials, at multiple sites of the muscle tested (patient 9). This pattern is evident when muscle fibers that are not under neuronal control fire spontaneously. The pre- and postoperative LEMG findings are shown in Table 2. Before surgery, 41 or 31 MU recruitment was noted in 8 patients. Other patients (patients 4, 7, 8, and 11) exhibited 21 MU recruitment during phonation. The vocal
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Table 4. Electromyographic and Glottal Configuration Findings. MU Recruitment Pt 1 2 3 4 5 6 7 8 9 10 11 12 P value
Thickness of Vocal Fold
Vertical Position of Vocal Fold
Preop
Postop
Preop
Postop
Preop
Postop
41 41 41 21 31 41 21 21 41 41 21 41
11 11 11 21 21 11 21 21 21 31 11 11
P P P P P NA NA P P = P P
P NA NA = P = P NA P = = P
= PS = = PS NA NA = = PS = PS
= NA NA = = = = NA = = = PS
.0065
.1740
.0580
Abbreivations: =, equal; MU, motor unit; NA, not assessed; P, paralyzed side, atrophic in comparison to unaffected side; PS, paralyzed side in superior position to unaffected side.
function of such patients was as poor as that of patients with 41 or 31 MU recruitment (Table 4). At 24 months following surgery, we again performed EMG testing. The results showed activation of the TA muscle along with improved vocal function in all patients who underwent the refined NMP implantation procedure (Table 4; Figure 2). One patient (patient 10) exhibited 31 MU recruitment 24 months after surgery, and the vocal function entered the near-normal range. Of the 12 patients (patient 4, 7, 8, and 11) who exhibited 21 MU recruitment before surgery, 4 had almost the same recruitment values 24 months after surgery. LEMG revealed significant postoperative improvements in voluntary MU recruitment, compared with preoperative MU recruitment during phonation (P = .0065; Table 4).
Evaluation of Glottal Configuration Based on Coronal Images During phonation, the vocal folds on the affected sides of 9 (90%) of 10 subjects before surgery were thinner than those on the healthy sides. Before surgery, the affected vocal fold was higher than the healthy fold during phonation in 4 subjects (40%). After surgery, the thickness of the affected fold in 4 (44.4%) of 9 patients was equal to that of the fold on the normal side during phonation (P = .174; Table 4). In 8 of 9 subjects (88.9%), the affected vocal fold was located at the same level as the healthy fold during phonation (P = .058; Table 4). Figure 3 shows the affected fold of patient 8 located at the same level as the healthy fold, which was thinner than the paralyzed fold before surgery (Figure 3A, B). Postoperatively, the affected fold attained the same thickness as the healthy fold during phonation (Figure 3C, D).
Discussion Laryngeal reinnervation affords the laryngologist another tool aiding vocal rehabilitation after UVFP. Although Tucker11 and May and Beery12 reported on the effectiveness of NMP flap implantation in treating breathy dysphonia due to UVFP, this procedure did not subsequently gain wide use. Previously, we reported that refined NMP flap implantation with AA, when used to treat UVFP, afforded excellent vocal function after surgery.15,16 In this refined technique, the NMP flap is harvested from the SH muscle, whereas Tucker11,24 and May and Beery12 raised the NMP flap from the omohyoid (OH) muscle. The AC branch to the SH muscle is thicker than that to the OH muscle and hence contains a larger number of regenerating axons. During surgery, an electrical stimulator was used to confirm the functionality of the AC. In addition, a cartilage window was made, and precise placement of the NMP flap onto the TA muscle was undertaken under microscopic control. In our present series of patients, perceptual and acoustic analyses, MPT, and MFR showed that they developed nearnormal ranges of vocal function over 24 months after surgery. Postoperative videostroboscopy revealed that patients treated with this procedure achieved complete glottal closure, with regular and even amplitudes on both sides of the vocal fold during phonation. Apposition of the symmetrical structures observed on videostroboscopy allowed the 2 vocal folds to oscillate both synchronously and symmetrically, thus reducing aperiodicity and perturbation and resulting in the production of a normally perceived tone. This was associated with significant improvements in postoperative perceptual evaluations (grade, breathiness, and asthenia) and acoustic data (jitter, shimmer, and HNR). Turning to voluntary MU recruitment in the TA/LCA muscle complex of the affected vocal fold during phonation, 7 cases lacked MUP, 5 exhibited mixed-type interference,
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Figure 2. Laryngeal electromyographic findings of a representative patient (patient 12). Recruitment of the affected fold exhibited no interference preoperatively. Postoperative recruitment of the reinnervated fold was associated with full interference.
Figure 3. Coronal reconstruction images (patient 8). The affected fold is thinner (thin arrow). At 24 months after surgery, the affected fold is the same thickness as the unaffected fold (thick arrow).
and no case presented with full interference preoperatively. This suggests that reinnervation of laryngeal muscles occurred in most UVFP patients over time after the onset of UVFP. This represents so-called ‘‘subclinical reinnervation.’’ If such reinnervation does not adequately restore neuronal function to the laryngeal muscles, the affected vocal fold remains paralyzed. However, subclinical reinnervation may help to prevent laryngeal muscle atrophy to some extent. In addition, some studies have found that the laryngeal muscle may retain an ability to receive regenerating nerve axons, even after long-term denervation.25,26 Such findings support the feasibility of delayed laryngeal reinnervation to treat UVFP. Patient 10 exhibited greatly decreased recruitment (31) 24 months
after surgery, with vocal fold function in the near-normal range. In an attempt to explain this result, there is a possibility that the AA procedure was successful despite a failure in the NMP flap implantation. This would result in improved vocal outcome with a seemingly paradoxical decreased recruitment value. Alternatively, there also exists the possibility that the monopolar electrode did not detect the TA muscle reinnervation area of the NMP flap implantation. It should be noted that were this the case, there might be limitations in the use of EMG electrodes in the measurement of MU recruitment. We previously assessed laryngeal muscle activity in UVFP patients using LEMG, aerodynamic analysis, and evaluation of glottal configuration via 3DCT.21 It was shown that MU recruitment affected the vertical position of the damaged fold during phonation. In the present study, before surgery, the vocal folds on the affected sides in 9 of 10 patients were thinner than those on the healthy sides during phonation. After surgery, the thickness of affected folds in 4 of 9 patients was equal to that of the fold on the normal side during phonation. This suggests that application of the refined NMP flap implantation improves TA/LCA muscle tone during phonation. In terms of vertical position, in 8 of 9 patients (88.9%), the affected fold attained a position, postoperatively, equal to that of the healthy fold. In 4 of the 8 patients (50%), the thickness of the affected folds was equal to that of the folds on the healthy side. Thus, reinnervation of the TA muscle by refined NMP flap implantation and AA was successful when used to equalize the vertical positions of the 2 folds. In the present work, LEMG revealed a significant increase, postoperatively, in the density of MU potentials in the TA/ LCA muscle complex during phonation. Postoperative EMG showed that the affected laryngeal muscles were successfully reinnervated via refined NMP flap implantation and that the TA/LCA muscle complex was activated by phonation. Preoperative LEMG showed that half of our patients may have
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maintained partial RLN innervation; NMP flap implantation into such TA/LCA muscle complexes either did not affect, or improved, postoperative recruitment compared to the preoperative levels during phonation and afforded excellent postoperative vocal function. Aoyama et al27 found that NMP flap implantation efficiently reduced atrophic changes developing in TA muscles retaining partial RLN innervation in an animal model. Thus, NMP flap implantation may also be useful in the treatment of patients in whom partial innervation (subclinical reinnervation) of the TA muscle is suspected.
Conclusion In this study, the LEMG findings and coronal imaging suggested that NMP flap implantation enabled successful reinnervation of the laryngeal muscles of UVFP patients. Thus, refined NMP flap implantation with AA is an effective surgical combination for the treatment of the severe dysphonia associated with UVFP. Author Contributions Tetsuji Sanuki, design, data analysis, drafting and revising the manuscript, final approval of the version to be published; Eiji Yumoto, data analysis and revising the manuscript, final approval of the version to be published; Kohei Nishimoto, data acquisition of LEMG and coronal images and interpretation of data, revising the manuscript; Narihiro Kodama, data analysis of phonatory function and videostroboscopy, revising the manuscript; Haruka Kodama, data acquisition of LEMG and coronal images and interpretation of data, revising the manuscript; Ryosei Minoda, contribution to making the manuscript and interpretation of data.
Disclosures Competing interests: None. Sponsorships: None. Funding source: This work was supported by JSPS KAKENHI Grant Number 25293349.
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