Vocal Fold Insufficiency: How Effective is Injection Laryngoplasty? Short Term Clinical Outcomes

Abstract

Office based Injection Laryngoplasty has become a common and feasible method of addressing vocal fold insufficiency (VFI) resulting from a plethora of aetiologies. Contemporary to various injectates, Calcium Hydroxylapatite has met with great success across usage with various techniques. But, irrespective of the technique and injectate material, the burning question in mind of “realistic” clientele remains, “How soon will I have by voice back?”. Aim of this study is to evaluate the short term (3 months postoperative) effects of Injection Laryngoplasty in cases of VFI using Calcium Hydroxylapatite via trans cricothyroid route, in terms of both objective and subjective parameters. 12 patients with mean age of 35.67 years underwent vocal fold injections (via transnasal flexible fibreoptic laryngoscopic guided trans-cricothyroid membrane approach using CaHA) for VFI. The pre injection and 1, 2- and 3-months post injection scores’ changes in outcome measures in form of videostroboscopic parameters, Voice Handicap Index scores and acoustic analysis were compiled and analysed. 91.6% of patients showed statistically significant benefit after 3 months post injection. 0.1% patients showed loss of benefit of the CaHA material even 3 months post injection. Average length of benefit was 1-month post injection. No significant complication was observed in any patient. We conclude that the objective evidence of structural and functional improvement may be seen immediately post injection laryngoplasty, minimum of 3 months is required for evident improvement in patient’s perception of his own voice in terms of Quality of Life parameters.

Introduction

Vocal fold paralysis is not a rare clinical entity. The length and path of the laryngeal nerves makes them vulnerable to compromise from a variety of sources and many physicians, otorhinolaryngologists, surgeons, oncologists and endocrinologists encounter the consequences [1].

Vocal fold insufficiency (VFI) is most commonly due to injury of the recurrent laryngeal nerve, which results in vocal fold immobility. It may or may not involve the superior laryngeal nerve, and thus sensation of the larynx is variably affected [1].

The recurrent laryngeal nerve may be subjected to a variety of mechanical trauma. It may section during surgery, stretched or compressed acutely during surgical manipulation, or chronically by a mass growing adjacent of nerve. It may be invaded by malignancy or devascularized as a result of nearby surgical dissection [1, 2]. Treatments for VFI are based on symptoms and severity, and range from voice therapy to VF injection augmentation and laryngeal framework surgery [3]. The first modern surgical treatment for VFI was vocal fold injection of Teflon [3, 4]. Another treatment method for VFI was developed in 1974, when Isshiki et al. [5] introduced thyroplasty (medialization thyroplasty). Several implantation procedures and a variety of implant products have since been introduced and generally these phonosurgical techniques have been proven successful [3, 6, 7]. Often the particular technique preferred by laryngologists and patients is phonosurgical vocal fold injection. Injection is less invasive than medialization thyroplasty and may provide results that are equally durable and effective [3, 8].

With any of these procedures, a key obstacle has been the use of a satisfactory implant/injection material. The ideal injection material would be inert, biologically stable, and deliverable through a fine gauge needle [2, 3]. Since the initiation of the vocal fold injection augmentation techniques, many injectates have been tried. Notable among them were polytetrafluoroethylene, bovine or human collagen, absorbable gelatin sponge foam and autologous fat and fascia, but none of these have been proven successful and without significant complications in long term [3, 9, 10].

Consequently, the introduction of a calcium hydroxylapatite injectate material has been met with great interest. Calcium hydroxylapatite (CaHA) is a bioceramic compound of phosphate and calcium; it is inert and biologically stable. In the commercially available formulation, small particles of CaHA (25–125 microns) are suspended in an aqueous-based gel carrier. This design allows injectate to flow through needles as fine as 26-gauge. Biocompatibility studies have demonstrated that CaHA creates no antigenic or inflammatory responses. After injection in vocal folds, the gel carrier is absorbed; the small particles of calcium hydroxylapatite remain fixed in place. Surrounding tissue grows into the matrix of the implant as the gel is absorbed. Studies of the calcium hydroxylapatite implant formulation have found the implant to remain intact at the injection site with no evidence of migration or calcification of the CaHA for up to 5 years after injection [2, 3, 11, 12].

Preoperative evaluation of vocal fold insufficiency initially by indirect laryngoscopy or direct rigid laryngoscopy, gave way to the use of transnasal flexible fibreoptic endoscopy to modern videostroboscopy. Stroboscopy involves the use of high-speed flashes of light at a frequency slightly lower or higher than the frequency of the patient’s vocal fold vibrations. The image thus obtained is an optical illusion of slow motion based on Talbot’s law i.e. the persistence of an image on the retina for 0.2 s after exposure. Stroboscopy can be performed with either a flexible laryngoscope or a rigid 70° or 90° angled telescope. Rigid stroboscopy provides brighter, clearer and more magnified images [13].

In vocal fold insufficiency, distortion of the voice signal can be demonstrated by acoustic analysis. A variety of softwares are available for voice analysis [14]. Combination of laryngeal videostroboscopy and acoustic analysis in a dysphonic patient helps to evaluate vocal cord abnormalities in detail. However, these two modalities alone do not specifically evaluate the resulting handicap as the patient perceives it. Use of a structured questionnaire to evaluate the Quality of Life in these patients is required for this. One of the most widely used dysphonia specific Quality of Life questionnaire is the Voice Handicap Index (VHI) developed by Jacobson et al. [13, 15].

When faced with straightforward questions from patients—what are the chances that I will have my voice recovered? Will this therapy make the paralyzed vocal fold move again? And, most importantly—How soon is either of these likely to happen?—We are able to offer only the most approximate answers, based on a consensus that is rarely supported by unequivocal clinical evidence [1, 2, 16]. The goal of this study was to look at a cohort of patients from one institution who have received vocal fold injection augmentation with CaHA for pre-determined (and most common) indications and to study the results for those patients by using Videostroboscopy, Voice handicap index scores and acoustic analysis as outcome measures for a period up to 3 months. Our intent was to determine the very short-term results of CaHA vocal fold injection augmentation in this ‘‘realistic’’ patient population and to report any complications from our institution’s cohort.

Materials and Methods

An observational descriptive study was conducted between May 2014 and Dec 2016, where, 12 patients, with unilateral or bilateral vocal fold paresis or paralysis, diagnosed clinically and by videolaryngoscopy, with various aetiologies underwent vocal fold injection via transnasal flexible fibreoptic laryngoscopic trans cricothyroid membrane approach at Department of Otorhinolaryngology and head neck surgery in a tertiary care centre at Pune, India. Vocal fold injection of Calcium Hydroxylapatite (Radiesse voice^®) via percutaneous route were administered as an office procedure. All diagnosed cases of age between 15 and 65 years, suffering from unilateral and bilateral adductor or combined abductor and adductor insufficiency including paralysis, paresis and nerve damage were included in this study. Cases of unilateral or bilateral abductor palsy, those who were allergic to Calcium Hydroxylapatite; cases with systemic illness, progressive neurological diseases, on anticoagulants and/or with previous laryngeal surgeries or severe laryngeal trauma, and patients suffering from laryngeal malignancies were excluded. Due clearance was obtained from the Institutional Ethics Committee.

Methodology

A detailed history of presenting complaint, past history of chronic diseases, treatment history and personal history with emphasis on voice use was obtained. A detailed general, systemic and ENT examination was carried out in all the selected patients and documented on the proforma.

Diagnosis of vocal fold insufficiency was done based on the symptomatology and clinical examination including 90° Hopkin’s rod lens laryngoscopy and flexible fibreoptic laryngoscopy (in few cases where Hopkins’s Rod lens examination was not possible due to excessive gag reflex). Routine haematological, biochemical and radiological investigations required for pre-anaesthesia assessment were done. Patients were informed of all the risks, benefits and alternatives of participating in the study and an informed consent was obtained from all the patients.

All the patients were subjected to office based vocal fold injection of Calcium hydroxylapetite (Radiesse voice^®) by transnasal flexible fibreoptic laryngoscope assisted trans cricothyroid membrane approach via percutaneous route under local anaesthesia with superior laryngeal nerve block. Figure 1 depicts transnasal flexible fibreoptic laryngoscopic images of trans cricothyroid membrane approach for Injection laryngoplasty. Through images A to D (Fig. 1), needle can be seen advancing from left side and bulge of injectate over right true vocal cord. Post procedure all patients were kept under observation for 1 h. No significant complication was noted in any patient.

Fig. 1.

Trans-cricothyroid membrane approach for Injection laryngoplasty. Transnasal fibreoptic flexible laryngoscopic images. Through images a–d, needle can be seen advancing from left side and bulge of injectate over right true vocal cord

Outcome Measures

1. Videostroboscopy

Videostroboscopy performed using the stroboscope system consisting of a 90° rigid telescope which is illuminated by high performance light for stroboscopy. The output picture and sound were captured into a computer and analyzed. The stroboscopy parameters noted were (1) Symmetry of vocal cords (2) Mucosal wave on both vocal folds, and (3) Glottic closure (complete/incomplete).

• 2.Acoustic analysis

The voice of each patient was recorded in a sound-treated room with the microphone held at a distance of 30 cm from the patient. The signal was recorded without amplification or filtering to a desktop computer with Windows based operating system. Analysis was done using software and the values for following parameters were recorded, compared and analysed for all patients—(1) Fundamental frequency, (2) Jitter, (3) Shimmer, (4) S–Z ratio, and (5) Maximum phonation time.

• 3.Voice handicap index (VHI)

The VHI, which is comprised of a total 30 questions targeting the patient’s perception of her/his own voice was administered to all patients. The 30 questions in VHI measure Physical, Functional, Emotional and Total aspects of their voice problems. Possible scores could range from 0 to 120. A change of 18 points in the total score and 8 points in the subscales was considered significant.

Follow Up

All patients were followed up post procedure at 1 month, 2 months and 3 months. Assessment parameters of the patients include videostroboscopy, acoustic analysis and VHI.

Results

The study group consisted of 12 adults who underwent injection laryngoplasty using calcium hydroxylapetite as an office procedure via transnasal flexible fibreoptic laryngoscope assisted trans cricothyroid membrane approach via percutaneous route. All the patients were screened as per inclusion and exclusion criteria and selected without any gender bias. There were 10 males and 02 females in the study with ages between 23 and 55 years and mean age of 33 years with standard deviation of 2.23. Sex ratio for males and females was 5:1.

Etiology for these patients was variable. Out of 12 patients, 05 suffered vocal fold insufficiency due to thyroid surgery in past, 01 patient suffered road traffic accident and etiology in 06 patients remained idiopathic. History of smoking was present in 05 cases (41.6%). Malignancy was ruled out in all cases as part of exclusion criteria.

Most common diagnosis was right vocal fold palsy (41.67%) followed by left vocal fold palsy (25%), bilateral vocal fold paresis (16.67%), right vocal fold paresis (8.33%) and left vocal fold paresis (8.33%). The right-sided involvement was the most frequent type (50%); left sided was 33.33% and bilateral involvement 16.6% (Fig. 2).

Fig. 2.

Distribution of aetiologies of vocal fold insufficiency

Videostroboscopy

Three videostroboscopic parameters were assessed viz. Symmetry of vocal fold, mucosal wave pattern and glottic closure.

1. Symmetry of vocal folds

The vocal fold symmetry was present preoperatively in 41.66% cases. Postoperative assessment was done at 01 month, 02 months and 03 months. Assessment at 01 month postoperative showed that vocal fold symmetry was achieved in 83.33% cases. 02 out of 03 cases of left vocal fold palsy showed asymmetrical vocal folds. The vocal fold symmetry was achieved in 11 out of 12 patients of all diagnoses combined postoperatively at 3 months. The result was statistically significant with P value 0.025 (Wilcoxon signed rank test) (Fig. 3).

• 2.Mucosal wave pattern

Fig. 3.

Vocal fold symmetry: pre and post-operative assessment

Preoperative assessment showed that mucosal wave was preoperatively absent in all cases. Postoperative assessment at 1 month showed that 58.33% patients have achieved mucosal wave. This percentage increased to 75% in second month and 83.33% at the end of third month. 16.67% cases could not achieve mucosal wave even at the end of 3 months. At the end of 3 months, 83.33% cases achieved mucosal wave, this result was statistically significant with P value 0.005 (Wilcoxon signed ranks test) (Table 1).

1. Glottic closure

Table 1.

Mucosal wave pattern and Glottic closure—comparison of preoperative and 3rd month postoperative results

Total no of cases with preoperative absent mucosal wave	Total no of cases who achieved mucosal wave at end of 3 months	P value
12	10	0.005*

Total no of cases with preoperative incomplete glottic closure	Total no of cases who achieved complete glottic closure at end of 3 months	P value
12	11	0.001*

*Wilcoxon signed ranks test

Preoperatively all cases showed incomplete glottic closure. Only one case of left vocal fold palsy showed persistence of incomplete glottic closure postoperatively depicting failure of treatment modality in that case. 91.67% cases achieved complete glottic closure at 3rd month postoperative visit which was statistically significant with P value 0.001 (Wilcoxon signed ranks test) (Table 1).

Voice Handicap Index (VHI)

Four parameters in voice handicap index were compared pre and 1, 2- and 3-months post operatively. Parameters and comparison results are as per Table 2.

Table 2.

Voice handicap index scores—comparison of preoperative and postoperative results

S. no.	Voice Handicap Index Scores	Preoperative (n = 12)		Postoperative (n = 12)
				1 month		2 months		3 months
		Mean	SD	Mean	SD	Mean	SD	Mean	SD
1	Physical scores	32.67	2.27	10.67	6.44	5.58	7.84	5.42	9.74
2	Functional scores	30.25	1.87	14.08	5.89	10.08	5.91	10.25	6.95
3	Emotional scores	25.25	2.77	10.08	5.57	7.75	5.6	6.41	5.4
4	Total scores	88.17	4.42	34.83	16.9	23.42	18.6	22.33	21.71

Mean scores of physical, functional, emotional and total voice handicap indices were compared pre-operatively and 1 month, 2 months and 3 months postoperatively. The results were statistically significant with P value 0.001 (Student’s paired t test) (Table 3).

Table 3.

Mean Voice Handicap Index: pre and post-operative comparison

VHI	Preoperative	3 months postoperative	P value *
Mean physical score	32.67	5.42	0.001
Mean functional score	30.25	10.25	0.001
Mean emotional score	25.25	6.41	0.001
Mean total score	88.17	22.33	0.001

*Student’s paired t test

Acoustic Analysis

Five acoustic analysis parameters were studied pre-operatively and 1, 2 and 3 months postoperatively (Table 4). Statistical analysis was done comparing preoperative and 3 months postoperative data with 95% confidence of interval of difference for all parameters and results were statistically significant with P value 0.001 (Student’s paired t test) (Table 5).

Table 4.

Acoustic analysis parameters—pre and postoperative analysis

Period	Maximum phonation time		Fundamental frequency		Jitter		Shimmer		S/Z ratio
	Mean	SD	Mean	SD	Mean	SD	Mean	SD	Mean	SD
Preoperative	4.97	0.77	208.92	16.18	1.43	0.18	2.53	0.32	1.4	0.14
1 month postoperative	10.78	1.79	167	11.82	0.74	0.19	1.61	0.43	0.88	0.25
2 months postoperative	11.65	2.27	162.33	10.92	0.65	0.27	1.55	0.43	0.69	0.21
3 months postoperative	12.56	2.42	160.66	12.39	0.69	0.38	1.45	0.43	0.6	0.25

Table 5.

Pre and 3 months post op comparison of acoustic analysis parameters

Acoustic analysis parameter	Preoperative	3 months postoperative	P value*
Mean maximum phonation time	4.97	12.56	0.001
Mean fundamental frequency	208.92	160.66	0.001
Mean jitter	1.43	0.69	0.001
Mean shimmer	2.53	1.45	0.001
Mean S/Z ratio	1.4	0.6	0.001

*Student’s paired t test

Discussion

The primary intent of this study was to find out the very short-term benefit of injection laryngoplasty in cases of VFI, that is, vocal fold paralysis or paresis, both unilateral and bilateral in terms of endoscopic study, patients’ quality of life and acoustic study of their voice.

Enhancing quality of life by creating a more effective and understandable voice is the primary purpose of phonosurgical vocal fold injection. Thus, a patient’s subjective experience of improvement is the most important measure of a procedure’s efficacy [3, 8].

In this study, injection with the calcium hydroxylapatite produced successful results, with statistically significant number of fully evaluated patients reporting an improvement in voice quality.

Videostroboscopic Changes

In many studies, it has been observed that the vocal fold edge, glottal configuration, vibratory amplitude and mucosal wave are key factors observed during stroboscopy that affect the quality of the voice. Complete glottic closure results in greater vocal fold contact because of a regular edge, with generation of a greater subglottic pressure and better amplitude of cord vibration [13, 17]. In our study complete glottic closure was achieved in 91.67% patients as found at 3rd month postoperative visit.

Though there is rarity of literature comparing these videostroboscopic parameters in cases of vocal fold insufficiency pre and post injection laryngoplasty using Calcium Hydroxylapatite, but some studies prove statistically significant improvement in these stroboscopic parameters post injection laryngoplasty. Study done by Woo et al. [17] showed complete glottic closure in 73.3% of patients at 3rd month postoperative visit after injection laryngoplasty making our study comparable with theirs.

Acoustic Analysis

Our study showed statistically significant improvement in Maximum phonation time, Jitter, Shimmer and S/Z ratio at 3rd month postoperative visit in 11 out of 12 cases of vocal fold insufficiency. These results are comparable with studies by Woo et al. and Hughes and Morrison [17, 18].

Voice Handicap Index (VHI)

In our study statistically significant improvement was seen in functional, physical, emotional and total VHI scores as found on 3rd month postoperative visit. It is comparable with studies by Woo et al., Carroll and Rosen, Mohammed et al., and Rosen et al. [16–19].

Conclusions

With the review of literature and results of this study the conclusions drawn are as under:

1. Injection laryngoplasty is a highly effective modality for treatment of vocal fold insufficiency when used in carefully selected patients.

2. Calcium hydroxylapatite is a stable injectate material which can be effectively used for vocal fold augmentation in cases of unilateral or bilateral vocal fold paresis/paralysis under local anesthesia without any significant complications as an office procedure.

3. Objective evidence of structural and functional improvement in form of videostroboscopic parameters may be seen immediately post injection laryngoplasty.

4. Minimum of 2 months is required for evident improvement in acoustic parameters of patient’s voice.

5. As far as the patient’s perception of his quality of life is concerned, in terms of Voice Handicap Index parameters, it takes at least 3 months for any significant subjective improvement.

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interests.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Written informed consent was obtained from all individual participants included in the study.