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Cricothyroid Joint Abnormalities in Patients With Rheumatoid Arthritis
Cricothyroid Joint Abnormalities in Patients With Rheumatoid Arthritis *Ghina Berjawi, †Imad Uthman, ‡Lorice Mahfoud, ‡Sami Tanbouzi Husseini, ‡Jihad Nassar, *Aghiad Kotobi, and ‡Abdul-Latif H. Hamdan, *yzBeirut, Lebanon Summary: The objective of this study was to assess structural and functional abnormalities of the cricothyroid joint (CTJ) in patients with advanced rheumatoid arthritis (RA). A total of 19 subjects—11 patients with advanced RA and eight normal controls—were considered. All subjects underwent laryngeal endoscopy, acoustic analysis, and highresolution computerized tomography (HRCT). Vocal symptoms, such as hoarseness, loss of range, vocal fatigue, and dyspnea were inquired and acoustic parameters, mainly pitch range, fundamental frequency, habitual pitch, perturbation parameters, and noise-to-harmonic ratio (NHR) and voice turbulence index were measured. Frequencies and means were calculated for categorical and continuous variables. Cases and controls were compared with respect to acoustic analysis, HRCT findings and laryngeal symptoms using nonparametric tests, Mann-Whitney U test for continuous variables and Fishers exact test for categorical variables. Almost half of the patients with RA had loss range and two-thirds had vocal fatigue. Thirty-six percent experienced hoarseness compared with 25% in the control group. 9.1% had decrease in vocal fold mobility and 27% had moderate/severe edema of the vocal folds/arytenoids compared with none in the control group. HRCT showed narrowing in the CTJ in 81.8% and ankylosis in 9.1% compared with none in the control group. 45.5% had an increase in the CTJ density compared with 12.5% in the control group. Acoustic analysis revealed significant decrease in pitch range and maximum phonation time (MPT) and significant increase in perturbation parameters. CTJ is commonly affected in patients with RA. Functional disabilities are crucial especially in professional voice users. Proper awareness is important for early detection and intervention. Key Words: Rheumatoid arthritis–Cricothyroid joint–Pitch range–Computerized tomography.
INTRODUCTION Rheumatoid arthritis (RA) is a disease that affects diarthrodial joints and can present with articular and extra-articular lesions. Laryngeal involvement in patients with RA is common but usually subclinical. The incidence depends on the population studied and the diagnostic tests used.1,2 A high index of suspicion and a thorough understanding of the nature of this disease are needed to recognize laryngeal involvement. The diagnosis may be hard in view of the wide range of symptomatology and laryngeal findings present during the course of the disease. Up to 31% of patients may report laryngeal symptoms during the course of their disease in a study published by Lowry et al in 1960.3 Subsequent studies have shown an increase in the prevalence rate to 75% with histopathology laryngeal involvement reaching up to 90% in postmortem examination.4,5 The clinical manifestations may vary from mild, subtle nonspecific complaints, such as sore throat and dysphagia to lifethreatening conditions, such as stridor and airway obstruction. Obstructive symptoms may be common in up to 75% of patients with laryngeal involvement and these are attributed either to vocal fold pathology or to cricoarytenoid joint (CAJ) involvement. A review of 218 cases with immobility of both Accepted for publication June 19, 2009. This manuscript has no actual or potential conflict of interest. The study had no sources of funding. From the *Radiology Department, American University of Beirut, Beirut, Lebanon; yDepartment of Internal Medicine, American University of Beirut, Beirut, Lebanon; and the zOtolaryngology Department, American University of Beirut, Beirut, Lebanon. Address correspondence and reprint requests to Abdul-Latif H. Hamdan, Department of Otolaryngology, American University of Beirut, P.O. Box: 11-0236, Beirut, Lebanon. E-mail: [email protected] (A.-L.H.H.) Journal of Voice, Vol. 24, No. 6, pp. 732-737 0892-1997/$36.00 Ó 2010 The Voice Foundation doi:10.1016/j.jvoice.2009.06.005
vocal folds admitted for airway restoration revealed arytenoid cartilage fixation secondary to RA in 6.3% of the cases.6 The yield of imaging technique in the detection of CAJ involvement can go from 25% to 72% depending on the sensitivity of the technique used, with 58% of the patients being asymptomatic.7 In a study by Jurik and Pedersen et al, low-voltage radiography revealed osseous destruction of the CAJ in up to 45% of their 22 patients.8 High-resolution computed tomography (HRCT) scan seems to be more useful for early detection of CAJ arthritis, where the presence of cricoid cartilage erosion is often mistaken for an aggressive carcinoma of the larynx.9 Little attention has been paid to the cricothyroid joint (CTJ) in view of its nonsignificant contribution to the airway. Few studies in the literature have reported the involvement of this joint using plain radiographic studies.3,10 Being a true synovial joint, the CTJ might be affected in patients with RA. Structural abnormalities with subsequent functional limitations must be considered during the progression of this disease. Fixation of the CTJ may affect the speaking voice leading to changes in vocal pitch and a contracted range. As for the singing voice, integrity of the CTJ is crucial. Any structural abnormality can potentially lead to major vocal complaints, such as loss of range, pitch breaks, or inability to sustain a note. The purpose of this study is to investigate the presence of structural and functional abnormalities of the CTJ using radiologic imaging, namely HRCT, laryngeal endoscopy, acoustic analysis, and vocal history. MATERIALS AND METHODS A total of 19 subjects were enrolled in this study after signing the informed consent approved by the Institution Review Board at the American University of Beirut, Lebanon. Subjects were divided into 11 patients with advanced RA and eight
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age-matched normals as controls who were solicited as volunteers at our institution. The controls had demographic data similar to those of subjects with advanced RA. By advanced RA, we mean patients were receiving intravenous infliximad, recombinant antitumor necrosis factor-alpha monoclonal antibody. Demographic data included age and gender, duration of the disease, history of smoking, and gastroesophageal reflux disease. Each subject was asked for the presence or absence of the following: hoarseness, vocal fatigue, loss of range, and dyspnea. Hoarseness was defined as a change in voice quality, vocal fatigue as tiring of the voice and/or inability to sustain phonation. Subjects underwent acoustic analysis using VISI Pitch (Model 3300, Kay Elemetrics, Corp., Lincoln Park, NJ) with special attention to the pitch range. The test was repeated twice to have a better estimate of the measures. While the patient is seated in a quiet office, the patient’s vocal signal was recorded directly into the system using a condenser microphone at a distance of 15 cm from the mouth. The following acoustic variables were measured: average fundamental frequency, relative average perturbation, shimmer, noise-to-harmonic ratio (NHR), voice turbulence index, habitual pitch, pitch range, and maximum phonation time. The habitual pitch was measured by asking the subject to count to 10 in a normal voice. The maximum phonation time (MPT) was calculated by asking the subject to take a deep breath and sustain phonation for as long as he could. The pitch range was measured by asking the subject to phonate starting from a comfortable pitch to the high register and then from a comfortable pitch to the lower register. The remaining variables were measured by asking the subject to sustain the vowel ‘‘ah’’ for 2 seconds, using the voicequality assessment module of the VISI Pitch system. The subjects also underwent laryngeal examination in the same setup using fiberoptic nasopharyngeal laryngoscopy. We looked for the presence or absence of abnormal vocal fold mobility, bowing of the vocal folds, arytenoid deformities, and arytenoid/vocal fold edema. This later finding was graded as mild, moderate, and severe. Finally patients underwent HRCT of the larynx using Simens Sensation 64 (Siemens Medical Solutions USA,
TABLE 1. Baseline Demographic Data and Clinical Characteristics Variables
Patients with RA
Control
Number of patients Sex (M:F)
11 2:9
8 2:6
Age (y) Mean ± SD Range
48.5 ± 12.2 22–65
46.8 ± 10.5 25–64
Duration of the disease Mean ± SD 9.8 ± 5 Range 2-20
N/A N/A
Smoking GERD
4/8 4/8
6/11 6/11
Abbreviation: SD, standard deviation; GERD, gastroesophageal reflux disease.
TABLE 2. Laryngeal Symptoms Patients With RA (%)
Control (%)
P Value
Dyspnea Loss of range
18.2 45.5
0 0
0.202 0.047
Vocal fatigue No fatigue Mild Moderate
36.4 36.4 27.3
75.0 25.0 0
0.158 0.158 0.158
Hoarseness No hoarseness Mild Moderate
63.6 27.3 9.1
75.0 25.0 0
0.662 0.662 0.662
Symptoms
Inc., PA, USA). The acquisition was 5-mm contiguous images with 0.6-mm reconstruction at the CTJ and CAJ. The imaging study was performed while patients were breathing quietly. The following anatomical abnormalities were examined: ankylosis, erosion, density changes, narrowing of the CTJ space, and vocal fold thickening. Narrowing of the CTJ was defined as a decrease in the volume of the joint. Ankylosis was defined as a loss of the radiolucent intercartilaginous space. Density changes were defined as hyperdense or hypodense images of the CTJ. Frequencies and means were calculated for categorical and continuous variables, as appropriate. Cases and controls were compared with respect to acoustic analysis, computerized tomographic (CT) findings, and laryngeal symptoms using nonparametric tests, Mann-Whitney U test for continuous variables and Fisher’s exact test for categorical variables. Differences were considered significant for P < 0.05. All analysis was conducted using SPSS software (Version 16, Sun Microsystems, Inc., CA, USA). RESULTS Demographic data The male to female ratio in patients with RA was 2:9. The age ranged between 22 and 65 years with a mean of 48.5 years. The duration of the disease ranged from 2 to 20 years with a mean of 9.8 years. Almost half of the subjects were smokers and had history of gastroesophageal reflux. With respect to controls, the age ranged between 25 and 64 years with a mean of 46 years. Four out of the eight controls had gastroesophageal reflux and were smokers. See Table 1. Laryngeal symptoms Almost half the patients with RA had loss of range versus none in the control group, a difference that was statistically significant (P ¼ 0.047). Two-thirds had mild to moderate vocal fatigue compared with one-fourth of the control group, which had only mild vocal fatigue. None of the control subjects had dyspnea compared with 18% of the RA patients. Only 25% of the control group had a mild degree of hoarseness or change in voice quality compared with 36% of the patients with RA. See Table 2.
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TABLE 3. Laryngeal Findings on Endoscopy Laryngoscopic Findings No decrease in vocal cord mobility Decrease in vocal cord mobility Vocal cord edema No edema Mild Moderate/severe
Patients P With RA (%) Control (%) Value 90.9
100
0.381
9.1
0
0.381
36.4 36.4 27.3
75.0 25.0 0.0
0.298 0.298 0.298
FIGURE 2. Axial cut of a CT scan showing narrowing of right CTJ space.
Laryngoscopic findings Almost 10% of patients with RA had impaired vocal fold mobility and 27% had moderate to severe vocal fold edema compared with none in the control group. See Table 3. Computerized tomographic findings Ten patients with RA out of 11 had evidence of structural anatomical abnormalities of the CTJ compared with none in the control group. There was a statistically significant difference in the prevalence of CTJ space narrowing among patients with RA versus controls (81.8% vs. 0%). See Figures 1 and 2. There was also an increase in the incidence of CTJ-joint ankylosis and density changes compared with controls; however, the difference was not statistically significant. See Figures 3 and 4. None of the subjects with RA had evidence of CTJ erosion. With respect to the CAJ, the prevalence of narrowing was higher compared with controls. It is also worth noting that 27% of the patients with RA had vocal fold thickening. See Table 4. Acoustic analysis There was a significant difference in the pitch range, perturbation parameters, mainly relative average perturbation (RAP) and shimmer, and the MPT between the patients and control group. The pitch range and MPT were significantly reduced in the affected patients, whereas the RAP and shimmer were significantly higher. The fundamental frequency was higher
FIGURE 1. Axial cut of a CT scan showing normal CTJ space.
in patients with advanced RA compared with controls. However, the difference was not statistically significant. Careful comparison, taking into consideration stratification by gender, reveals that the increase is particularly present in females and not males (F0 ¼ 177.25 in females with RA vs. F0 ¼ 171.25 in female controls). There was no statistically significant difference in the remaining acoustic parameters. See Table 5. DISCUSSION The first report of laryngeal involvement in RA was described by Sir Morell Mackenzie in 1880.11 Since then, there have been several studies that have demonstrated a high prevalence of laryngeal abnormalities in patients with RA, with the incidence being higher in females compared with males.1–12 Most reports on laryngeal involvement in RA patients have focused on the CAJ because of the prevailing increase in incidence and the subsequent serious clinical implications. Acute laryngeal involvement can cause swelling of the vocal folds with airway obstruction, and chronic involvement can impair vocal fold mobility with resultant fixation and narrowing of the glottis. It became clear that involvement of the CAJ by RA starts with inflammation of the synovial lining that spreads to the articulating surfaces leading to fibrosis with consequent union and ankylosis of the joint.1,13 The movement of the paired, triangle-shaped arytenoid cartilages resting on the cricoid facet may be impaired in the vertical direction, anteroposteriorly or mediolaterally. Because of its strategic location, this impairment can affect both the voice and breathing. Inability of the vocal folds to assume the near total adduction position and maintaining it during sustained phonation can alter the vocal pitch, intensity, and duration. On the other hand, failure of the vocal folds to abduct during inspiration can result in airway obstruction. The diagnosis of cricoarytenoiditis is not always challenging because of the presence of laryngeal symptoms, even though these are often obscured by the other articular involvements. Bayar et al have previously reported that 66% of laryngeal symptoms are attributed to CAJ involvement.14. In our study, the CAJ was involved in close to half of the subjects, with vocal fatigue being present in two-thirds of the subjects and dyspnea in one-fifth. These symptoms could be explained on the basis of
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Cricothyroid Joint in Rheumatoid Arthritis
FIGURE 3. A. Axial cut of a CT scan showing left CTJ ankylosis. B. Coronal cut of a CT scan showing left CTJ ankylosis. impaired breathing support and/or control, or on the restricted mobility of the vocal folds, which may result in incomplete closure of the vocal folds, decreased glottal resistance, and increased mean glottal flow rate. On the other hand, cricothyroid involvement is not always clinically evident or reported by the affected individual. As we know, the CTJ is a pitch-regulating joint that is directly
FIGURE 4. Axial cut of HRCT scan showing an increase in the density of right CTJ.
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related to pitch range.15,16 Impaired mobility of this joint will hinder the rotatory movement because of the contraction of the vertical belly of the CTJ muscle and/or the translocation movement initiated by the diagonal belly of the same muscle. Both the rotational movement and translocation of the thyroid cartilage at the CTJ can be affected. The dynamics of the CTJ and the changes in the visor angle are important for the speaking voice and rather essential for the singing voice.17,18 Consequently, affected patients may complain of loss of range or a contracted range with limited ability to project the voice. In our study, almost half of the patients with RA had loss of range compared with none in the control group, a difference that reached statistical significance. None of the other laryngeal symptoms were significantly different. There was also a significant decrease in the pitch range compared with the control group, which can be theoretically attributed to the alterations in the biomechanical behavior of the CTJ. Laryngoscopy and laryngeal CT scan appear to be complementary investigations, as laryngoscopy tends to allow better evaluation of the mucosal lining and laryngeal biomechanics, whereas CT scanning enables evaluation of the anatomical and structural integrity of the larynx and its joints. On laryngoscopy, the prevalence of RA varied between 32% and 75% with the most common findings being asymmetry of the arytenoids, edema and redness in the acute stage, versus impaired mobility or bowing of the vocal folds in the chronic stage.13 Normal appearance of the larynx in patients with RA is also commonly seen. In our study, none of the laryngoscopic findings reached statistical difference compared with the control group despite the fact that our subjects had advanced RA. Impaired mobility was present in only 10% of the patients and significant redness in 27% of the cases. These findings are commensurate with the literature and can explain some of the laryngeal symptoms despite the fact that the correlation between laryngeal symptoms and laryngeal findings is poor.14 The incidence of laryngeal involvement radiologically in patients with RA is high and does not go in hand with the presence or absence of laryngeal symptoms. On CT scanning, the prevalence of CAJ abnormalities vary between 54% and 72%.7 The most commonly reported findings include cricoarytenoid prominence (46.6%), density and volume changes in the CAJ (46.6%), sublaxation (39.9%), decrease in the CAJ space (13.3%), narrowing in the piriform sinuses (33.3%), and irregularities in the contour of the CA joint (20%). Erosion and ankylosis seem to be less common.14 What is interesting is that, invariably, the radiological findings can be seen at or before the clinical findings appear. In our study, the prevalence of CAJ abnormalities was less pronounced compared with the literature and the most common findings were narrowing of the CAJ space and increase in the soft tissue density. What is remarkable in our study is the high prevalence of CTJ involvement in more than 90% of patients with RA compared with none in the control group. The involvement was unilateral in all cases, mainly narrowing of the joint space in more than two-thirds of the patients and ankylosis in almost 10% of the cases. Only CTJ space narrowing reached statistical significance compared with controls. More than one structural
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of diminished pitch range are the overall physical condition of the subject and the presence or absence of neurological diseases. Subjects in good physical condition have larger phonational ranges than those in poor condition as in patients with advanced RA as reported by R.J. Baken.21 The positioning of subject while the frequency range is being determined also plays a role. Both upper and lower fundamental frequency limits seem to be reduced in the supine position, with a consequent reduction in the pitch range. In our study the pitch range was determined while patients were in the sitting position. It is also worth noting that intrasubject variability by at least a few semitones has also been reported.22 Previous radiological study using low-voltage radiographic technique has shown changes in the CTJ as osseous destruction of the cricoid and/or inferior thyroid cornu at the joint in four out of 17 females.8 In our study, there were no signs of erosion or destruction of either the thyroid or cricoid cartilages. Another important radiological finding worth noting in our study is the presence of vocal fold thickening which can be explained by the endoscopic finding of vocal fold edema in roughly the same percentage of patients. The radiological vocal fold thickening can also be attributed to the virtual shortening of the vocal fold secondary to incomplete or inefficient lengthening. With respect to the acoustic analysis, most of the results were substantiated by the laryngeal findings and symptoms. The inflammation affecting the vocal folds can result in changes in the vocal fold behavior and an increase in the perturbation parameters. Cycle-to-cycle variation in pitch and intensity may be affected by changes in the consistency and thickness of the vocal fold as seen in our study. It is also worth noting the increase in F0 in females with RA (177.25 vs. 171.25 Hz in normals), even though it was not significant. This could be accounted for by the limitation in the movement of the vocal folds, as more than 90% and close to 50% of patients with RA had CTJ and CAJ involvement, respectively. The impaired mobility can lead to a decrease in the muscle mass with a resulting increase in frequency. This explanation remains hypothetical
TABLE 4. HRCT Findings Patients Control P (%) (%) Value
CT Findings Ankylosis CTJ Ankylosis CAJ Increase in the density of CTJ Increase in the density of CAJ Narrowing in CTJ space Narrowing in CAJ space Vocal fold thickening
9.1 0 45.5 9.1 81.8 45.5 27.3
0 0 12.5 12.5 0.0 12.5 0.0
0.381 0.228 0.127 0.811 0.000 0.127 0.107
abnormality was present in almost half of the subjects. Density changes together with either narrowing of the intercartilaginous space or ankylosis were present in five out of the nine subjects. It seems that CTJ is affected more commonly than the CAJ. Not all subjects who had a decrease in CTJ space had a decrease in CAJ space (only five out of nine), whereas all patients who had a decrease in CAJ space had a decrease in the CTJ space. With respect to density changes, the increase in density was also more pronounced in the CTJ compared with the CAJ. Not all patients who had an increase in CTJ density had an increase in CAJ density. Only one patient had an increase in CAJ density compared with five with respect to the CTJ. These findings can partially explain the decrease in pitch range and the loss of range reported in 45% of our patients. Clearly, the radiological changes of the CTJ may play a role but are not the major determinants of the vocal-range changes reported by patients with RA. The loss of range can be the result of a decrease in the agility and flexibility of the vocal folds or the variations in the airflow in relation to breathing support and control, which might be affected in patients with advanced RA. Pulmonary complications caused by RA are a clinically relevant aspect of this chronic arthropathy. Those complications can involve all parts of the thorax, including the lung parenchyma, the pleura, and the thoracic cage.19,20 Other causes
TABLE 5. Acoustic Analysis Patients (n ¼ 11)
Control (n ¼ 8)
Mean—Female (F0 ¼ 177.25) and Male (F0 ¼ 92.80)
SD
Mean—Female (F0 ¼ 171.25) and Male (F0 ¼ 99.42)
SD
P Value
F0 RAP Shimmer NHR VTI MPT
162.197 1.71 6.84 0.16 0.043 9.73
45.15 0.78 2.86 0.73 0.028 2.61
153.13 0.97 3.40 0.22 0.036 16.24
41.58 0.33 1.05 0.25 0.012 1.30
0.62 0.021 0.002 0.869 0.901 0.002
Habitual pitch Range of pith (Hz) Maximum (Hz) Minimum (Hz)
150.02 167.46 287.8 120.44
Acoustic Analysis
35.72 95.05 109.78 40.31
148.92 277.28 396.28 119
Abbreviation: SD, standard deviation; NHR, noise-to-harmonic ratio; VTI, Voice Turbulence Index; MPT, maximum phonation time.
43.70 100.28 70.76 34.85
0.869 0.029 0.018 0.934
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Cricothyroid Joint in Rheumatoid Arthritis
and needs further investigation. The lack of similar findings in male F0 could be attributed to the relatively small number of cases (only two), which prohibits us from drawing any conclusion. With respect to vocal-range changes, we compared in the RA group the pitch range and prevalence of loss of range in those with abnormal CTJ versus those with normal CTJ. Only one subject had normal CTJ on CT scan and the remaining 10 had either ankylosis or narrowing in the joint space. The patient with normal CTJ had no loss of range clinically, and the pitch range was 147.59 Hz, whereas 50% of the patients with abnormal CTJ had loss of range and the average pitch range was 169.45 Hz. No statistically significant conclusion can be drawn by comparing the pitch range in the two subgroups in view of the small number of cases (one vs. 10). Closer examination of the data reveals that the maximum pitch was lower in subjects with abnormal CTJ (284.47 vs. 321.9 Hz), probably indicating CTJ dysfunction. One of the major limitations of our study is the small number of cases and the fact that the radiological evaluation was performed when the vocal folds were not in the phonatory position, that is, the actual contraction of the cricothyroid muscle was not monitored or measured electromyographically or endoscopically. It is also worth mentioning the normal anatomical variation of the CTJ by site as described by Maue-Dickson et al in his cadaveric dissection report, over which we had no control or actual measure in our study.23 The variation by site plays a counterintuitive role in the association between the structural anomalies seen on CT scan and the functional limitations, namely the loss of range and reduced pitch range. Nevertheless, our study is the first study that investigates radiologically, using CT scan, the structural changes in the CTJ, and acoustically, the vocal range in subjects with advanced RA compared with controls. Definitely future investigations to further elucidate the aforementioned changes and their impact on daily life especially in professional voice users are warranted.
CONCLUSION In summary, this study demonstrates that the incidence of anatomical abnormalities in the CTJ using HRCT is higher in patients with RA compared with a matched control group. Patients also demonstrated functional abnormalities, namely a contracted vocal range, clinically and a decrease in the pitch range on acoustic analysis affecting mainly the high notes. The long-term consequences of the radiological abnormalities of the CTJ are not known. Both the speaking voice and the professional voice may suffer from these structural and functional abnormalities.
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REFERENCES 1. Geterud A. Rheumatoid arthritis in the larynx. Scan J Rheumatol. 1991;20: 215. 2. Bienenstock H, Ehrlich GE, Freyberg RH. Rheumatoid arthritis of the cricoarytenoid joints: a clinicopathologic study. Arthritis Rheum. 1963;6: 48–63. 3. Lawry GV, Finerman ML, Hanafee WN, Mancuso AA, Fan PT, Bluestone R. Laryngeal involvement in rheumatoid arthritis. A clinical, laryngoscopic and computerized tomographic study. Arthritis Rheum. 1984;27:873–882. 4. Pearson JE. Rheumatoid arthritis of the larynx. Br Med J. 1957;2:1047. 5. Copeman WS. Rheumatoid arthritis of the cricoarytenoid joints. Br Med J. 1957;1:1398–1399. 6. Eckel HE, Wittekindt C, Schroeder U, Klussmann JP, Sittel C. Management of bilateral arytenoids cartilage fixation versus recurrent laryngeal nerve paralysis. Ann Otol Rhinol Laryngol. 2003;112:103–108. 7. Brazeau-Lamontagne L, Charlin B, Levesque RY, Lussier A. Cricoarytenoiditis: CT assessment in rheumatoid arthritis. Radiology. 1986;158: 463–466. 8. Jurik AG, Pederson U. Rheumatoid arthritis of the cricoarytenoid and cricothyroid joints: a radiological and clinical study. Clin Radiol. 1984;35: 233–236. 9. Chen JJ, Branstetter BF, Myers EU. Cricoarytenoid rheumatoid arthritis: an important consideration in aggressive lesions of the larynx. ANJR. 2005;26: 970–972. 10. Bridger MWM, Jahn AF, Nostrand AWP. Laryngeal rheumatoid arthritis. Laryngoscope. 1980;90:296–303. 11. Mackenzie M. Diseases of the pharynx, larynx and trachea. New York: William Wood & Co.; 1880. 12. Voulgari PV, Papazisi D, Bai M, Zagorianakou P, Assimakopoulos D, Drosos A. Laryngeal involvement in rheumatoid arthritis. Rheumatol Int. 2005;25:321–325. 13. Bastian RW. Chronic non-specific disease of the larynx. In: Ballenger JJ, ed. Diseases of the Nose, Throat, Ear, Head and Neck. 14th ed. London: Lea and Febiger; 1991:616–630. 14. Bayar N, Kara SA, Keles I, Koc C, Altinok D, Orkun S. Cricoarytenoiditis in reumatoid arthritis: radiologic and clinical study. J Otolaryngol. 2003;32:373–378. 15. Isshiki N, Taira T, Tanabe M. Surgical alteration of the vocal pitch. J Otolaryngol. 1983;12:335–340. 16. Hong KH, Kim HK, Kim YH. The role of pars recta and pars oblique of cricothyroid muscle in speech production. J Voice. 2001;15:512–518. 17. Isshiki N. Mechanical and dynamic aspects of voice production as related to voice therapy and phonosurgery. J Voice. 1998;12:125–137. 18. Sataloff RT. Vocal Health and Pedagogy. San Diego, California: Singular Publishing Group, Inc. 1998: 5-45. 19. Bankier AA, Fleischmann D, Kiener HP, Wiesmayr MN, Herold CJ. Pleural and pulmonary changes within the scope of rheumatoid arthritis. Radiologe. 1996;36:637–645. 20. Bouros D, Pneumatikos I, Tzouvelekis A. Pleural involvement in systemic autoimmune disorders. Respiration. 2008;75:361–371. 21. Baken RJ. Clinical Measurement of Speech and Voice. Boston: College Hill Press; 1996: 162-166. 22. Gelfer MP. Stability in phonational frequency range. J Commun Disord. 1989;22:181–192. 23. Maue-Dickson W. The craniofacial complex in cleft lip and palate: an update review of anatomy and function. Cleft Palate J. 1979;16: 291–317.
INTRODUCTION Rheumatoid arthritis (RA) is a disease that affects diarthrodial joints and can present with articular and extra-articular lesions. Laryngeal involvement in patients with RA is common but usually subclinical. The incidence depends on the population studied and the diagnostic tests used.1,2 A high index of suspicion and a thorough understanding of the nature of this disease are needed to recognize laryngeal involvement. The diagnosis may be hard in view of the wide range of symptomatology and laryngeal findings present during the course of the disease. Up to 31% of patients may report laryngeal symptoms during the course of their disease in a study published by Lowry et al in 1960.3 Subsequent studies have shown an increase in the prevalence rate to 75% with histopathology laryngeal involvement reaching up to 90% in postmortem examination.4,5 The clinical manifestations may vary from mild, subtle nonspecific complaints, such as sore throat and dysphagia to lifethreatening conditions, such as stridor and airway obstruction. Obstructive symptoms may be common in up to 75% of patients with laryngeal involvement and these are attributed either to vocal fold pathology or to cricoarytenoid joint (CAJ) involvement. A review of 218 cases with immobility of both Accepted for publication June 19, 2009. This manuscript has no actual or potential conflict of interest. The study had no sources of funding. From the *Radiology Department, American University of Beirut, Beirut, Lebanon; yDepartment of Internal Medicine, American University of Beirut, Beirut, Lebanon; and the zOtolaryngology Department, American University of Beirut, Beirut, Lebanon. Address correspondence and reprint requests to Abdul-Latif H. Hamdan, Department of Otolaryngology, American University of Beirut, P.O. Box: 11-0236, Beirut, Lebanon. E-mail: [email protected] (A.-L.H.H.) Journal of Voice, Vol. 24, No. 6, pp. 732-737 0892-1997/$36.00 Ó 2010 The Voice Foundation doi:10.1016/j.jvoice.2009.06.005
vocal folds admitted for airway restoration revealed arytenoid cartilage fixation secondary to RA in 6.3% of the cases.6 The yield of imaging technique in the detection of CAJ involvement can go from 25% to 72% depending on the sensitivity of the technique used, with 58% of the patients being asymptomatic.7 In a study by Jurik and Pedersen et al, low-voltage radiography revealed osseous destruction of the CAJ in up to 45% of their 22 patients.8 High-resolution computed tomography (HRCT) scan seems to be more useful for early detection of CAJ arthritis, where the presence of cricoid cartilage erosion is often mistaken for an aggressive carcinoma of the larynx.9 Little attention has been paid to the cricothyroid joint (CTJ) in view of its nonsignificant contribution to the airway. Few studies in the literature have reported the involvement of this joint using plain radiographic studies.3,10 Being a true synovial joint, the CTJ might be affected in patients with RA. Structural abnormalities with subsequent functional limitations must be considered during the progression of this disease. Fixation of the CTJ may affect the speaking voice leading to changes in vocal pitch and a contracted range. As for the singing voice, integrity of the CTJ is crucial. Any structural abnormality can potentially lead to major vocal complaints, such as loss of range, pitch breaks, or inability to sustain a note. The purpose of this study is to investigate the presence of structural and functional abnormalities of the CTJ using radiologic imaging, namely HRCT, laryngeal endoscopy, acoustic analysis, and vocal history. MATERIALS AND METHODS A total of 19 subjects were enrolled in this study after signing the informed consent approved by the Institution Review Board at the American University of Beirut, Lebanon. Subjects were divided into 11 patients with advanced RA and eight
Ghina Berjawi, et al
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age-matched normals as controls who were solicited as volunteers at our institution. The controls had demographic data similar to those of subjects with advanced RA. By advanced RA, we mean patients were receiving intravenous infliximad, recombinant antitumor necrosis factor-alpha monoclonal antibody. Demographic data included age and gender, duration of the disease, history of smoking, and gastroesophageal reflux disease. Each subject was asked for the presence or absence of the following: hoarseness, vocal fatigue, loss of range, and dyspnea. Hoarseness was defined as a change in voice quality, vocal fatigue as tiring of the voice and/or inability to sustain phonation. Subjects underwent acoustic analysis using VISI Pitch (Model 3300, Kay Elemetrics, Corp., Lincoln Park, NJ) with special attention to the pitch range. The test was repeated twice to have a better estimate of the measures. While the patient is seated in a quiet office, the patient’s vocal signal was recorded directly into the system using a condenser microphone at a distance of 15 cm from the mouth. The following acoustic variables were measured: average fundamental frequency, relative average perturbation, shimmer, noise-to-harmonic ratio (NHR), voice turbulence index, habitual pitch, pitch range, and maximum phonation time. The habitual pitch was measured by asking the subject to count to 10 in a normal voice. The maximum phonation time (MPT) was calculated by asking the subject to take a deep breath and sustain phonation for as long as he could. The pitch range was measured by asking the subject to phonate starting from a comfortable pitch to the high register and then from a comfortable pitch to the lower register. The remaining variables were measured by asking the subject to sustain the vowel ‘‘ah’’ for 2 seconds, using the voicequality assessment module of the VISI Pitch system. The subjects also underwent laryngeal examination in the same setup using fiberoptic nasopharyngeal laryngoscopy. We looked for the presence or absence of abnormal vocal fold mobility, bowing of the vocal folds, arytenoid deformities, and arytenoid/vocal fold edema. This later finding was graded as mild, moderate, and severe. Finally patients underwent HRCT of the larynx using Simens Sensation 64 (Siemens Medical Solutions USA,
TABLE 1. Baseline Demographic Data and Clinical Characteristics Variables
Patients with RA
Control
Number of patients Sex (M:F)
11 2:9
8 2:6
Age (y) Mean ± SD Range
48.5 ± 12.2 22–65
46.8 ± 10.5 25–64
Duration of the disease Mean ± SD 9.8 ± 5 Range 2-20
N/A N/A
Smoking GERD
4/8 4/8
6/11 6/11
Abbreviation: SD, standard deviation; GERD, gastroesophageal reflux disease.
TABLE 2. Laryngeal Symptoms Patients With RA (%)
Control (%)
P Value
Dyspnea Loss of range
18.2 45.5
0 0
0.202 0.047
Vocal fatigue No fatigue Mild Moderate
36.4 36.4 27.3
75.0 25.0 0
0.158 0.158 0.158
Hoarseness No hoarseness Mild Moderate
63.6 27.3 9.1
75.0 25.0 0
0.662 0.662 0.662
Symptoms
Inc., PA, USA). The acquisition was 5-mm contiguous images with 0.6-mm reconstruction at the CTJ and CAJ. The imaging study was performed while patients were breathing quietly. The following anatomical abnormalities were examined: ankylosis, erosion, density changes, narrowing of the CTJ space, and vocal fold thickening. Narrowing of the CTJ was defined as a decrease in the volume of the joint. Ankylosis was defined as a loss of the radiolucent intercartilaginous space. Density changes were defined as hyperdense or hypodense images of the CTJ. Frequencies and means were calculated for categorical and continuous variables, as appropriate. Cases and controls were compared with respect to acoustic analysis, computerized tomographic (CT) findings, and laryngeal symptoms using nonparametric tests, Mann-Whitney U test for continuous variables and Fisher’s exact test for categorical variables. Differences were considered significant for P < 0.05. All analysis was conducted using SPSS software (Version 16, Sun Microsystems, Inc., CA, USA). RESULTS Demographic data The male to female ratio in patients with RA was 2:9. The age ranged between 22 and 65 years with a mean of 48.5 years. The duration of the disease ranged from 2 to 20 years with a mean of 9.8 years. Almost half of the subjects were smokers and had history of gastroesophageal reflux. With respect to controls, the age ranged between 25 and 64 years with a mean of 46 years. Four out of the eight controls had gastroesophageal reflux and were smokers. See Table 1. Laryngeal symptoms Almost half the patients with RA had loss of range versus none in the control group, a difference that was statistically significant (P ¼ 0.047). Two-thirds had mild to moderate vocal fatigue compared with one-fourth of the control group, which had only mild vocal fatigue. None of the control subjects had dyspnea compared with 18% of the RA patients. Only 25% of the control group had a mild degree of hoarseness or change in voice quality compared with 36% of the patients with RA. See Table 2.
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TABLE 3. Laryngeal Findings on Endoscopy Laryngoscopic Findings No decrease in vocal cord mobility Decrease in vocal cord mobility Vocal cord edema No edema Mild Moderate/severe
Patients P With RA (%) Control (%) Value 90.9
100
0.381
9.1
0
0.381
36.4 36.4 27.3
75.0 25.0 0.0
0.298 0.298 0.298
FIGURE 2. Axial cut of a CT scan showing narrowing of right CTJ space.
Laryngoscopic findings Almost 10% of patients with RA had impaired vocal fold mobility and 27% had moderate to severe vocal fold edema compared with none in the control group. See Table 3. Computerized tomographic findings Ten patients with RA out of 11 had evidence of structural anatomical abnormalities of the CTJ compared with none in the control group. There was a statistically significant difference in the prevalence of CTJ space narrowing among patients with RA versus controls (81.8% vs. 0%). See Figures 1 and 2. There was also an increase in the incidence of CTJ-joint ankylosis and density changes compared with controls; however, the difference was not statistically significant. See Figures 3 and 4. None of the subjects with RA had evidence of CTJ erosion. With respect to the CAJ, the prevalence of narrowing was higher compared with controls. It is also worth noting that 27% of the patients with RA had vocal fold thickening. See Table 4. Acoustic analysis There was a significant difference in the pitch range, perturbation parameters, mainly relative average perturbation (RAP) and shimmer, and the MPT between the patients and control group. The pitch range and MPT were significantly reduced in the affected patients, whereas the RAP and shimmer were significantly higher. The fundamental frequency was higher
FIGURE 1. Axial cut of a CT scan showing normal CTJ space.
in patients with advanced RA compared with controls. However, the difference was not statistically significant. Careful comparison, taking into consideration stratification by gender, reveals that the increase is particularly present in females and not males (F0 ¼ 177.25 in females with RA vs. F0 ¼ 171.25 in female controls). There was no statistically significant difference in the remaining acoustic parameters. See Table 5. DISCUSSION The first report of laryngeal involvement in RA was described by Sir Morell Mackenzie in 1880.11 Since then, there have been several studies that have demonstrated a high prevalence of laryngeal abnormalities in patients with RA, with the incidence being higher in females compared with males.1–12 Most reports on laryngeal involvement in RA patients have focused on the CAJ because of the prevailing increase in incidence and the subsequent serious clinical implications. Acute laryngeal involvement can cause swelling of the vocal folds with airway obstruction, and chronic involvement can impair vocal fold mobility with resultant fixation and narrowing of the glottis. It became clear that involvement of the CAJ by RA starts with inflammation of the synovial lining that spreads to the articulating surfaces leading to fibrosis with consequent union and ankylosis of the joint.1,13 The movement of the paired, triangle-shaped arytenoid cartilages resting on the cricoid facet may be impaired in the vertical direction, anteroposteriorly or mediolaterally. Because of its strategic location, this impairment can affect both the voice and breathing. Inability of the vocal folds to assume the near total adduction position and maintaining it during sustained phonation can alter the vocal pitch, intensity, and duration. On the other hand, failure of the vocal folds to abduct during inspiration can result in airway obstruction. The diagnosis of cricoarytenoiditis is not always challenging because of the presence of laryngeal symptoms, even though these are often obscured by the other articular involvements. Bayar et al have previously reported that 66% of laryngeal symptoms are attributed to CAJ involvement.14. In our study, the CAJ was involved in close to half of the subjects, with vocal fatigue being present in two-thirds of the subjects and dyspnea in one-fifth. These symptoms could be explained on the basis of
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Cricothyroid Joint in Rheumatoid Arthritis
FIGURE 3. A. Axial cut of a CT scan showing left CTJ ankylosis. B. Coronal cut of a CT scan showing left CTJ ankylosis. impaired breathing support and/or control, or on the restricted mobility of the vocal folds, which may result in incomplete closure of the vocal folds, decreased glottal resistance, and increased mean glottal flow rate. On the other hand, cricothyroid involvement is not always clinically evident or reported by the affected individual. As we know, the CTJ is a pitch-regulating joint that is directly
FIGURE 4. Axial cut of HRCT scan showing an increase in the density of right CTJ.
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related to pitch range.15,16 Impaired mobility of this joint will hinder the rotatory movement because of the contraction of the vertical belly of the CTJ muscle and/or the translocation movement initiated by the diagonal belly of the same muscle. Both the rotational movement and translocation of the thyroid cartilage at the CTJ can be affected. The dynamics of the CTJ and the changes in the visor angle are important for the speaking voice and rather essential for the singing voice.17,18 Consequently, affected patients may complain of loss of range or a contracted range with limited ability to project the voice. In our study, almost half of the patients with RA had loss of range compared with none in the control group, a difference that reached statistical significance. None of the other laryngeal symptoms were significantly different. There was also a significant decrease in the pitch range compared with the control group, which can be theoretically attributed to the alterations in the biomechanical behavior of the CTJ. Laryngoscopy and laryngeal CT scan appear to be complementary investigations, as laryngoscopy tends to allow better evaluation of the mucosal lining and laryngeal biomechanics, whereas CT scanning enables evaluation of the anatomical and structural integrity of the larynx and its joints. On laryngoscopy, the prevalence of RA varied between 32% and 75% with the most common findings being asymmetry of the arytenoids, edema and redness in the acute stage, versus impaired mobility or bowing of the vocal folds in the chronic stage.13 Normal appearance of the larynx in patients with RA is also commonly seen. In our study, none of the laryngoscopic findings reached statistical difference compared with the control group despite the fact that our subjects had advanced RA. Impaired mobility was present in only 10% of the patients and significant redness in 27% of the cases. These findings are commensurate with the literature and can explain some of the laryngeal symptoms despite the fact that the correlation between laryngeal symptoms and laryngeal findings is poor.14 The incidence of laryngeal involvement radiologically in patients with RA is high and does not go in hand with the presence or absence of laryngeal symptoms. On CT scanning, the prevalence of CAJ abnormalities vary between 54% and 72%.7 The most commonly reported findings include cricoarytenoid prominence (46.6%), density and volume changes in the CAJ (46.6%), sublaxation (39.9%), decrease in the CAJ space (13.3%), narrowing in the piriform sinuses (33.3%), and irregularities in the contour of the CA joint (20%). Erosion and ankylosis seem to be less common.14 What is interesting is that, invariably, the radiological findings can be seen at or before the clinical findings appear. In our study, the prevalence of CAJ abnormalities was less pronounced compared with the literature and the most common findings were narrowing of the CAJ space and increase in the soft tissue density. What is remarkable in our study is the high prevalence of CTJ involvement in more than 90% of patients with RA compared with none in the control group. The involvement was unilateral in all cases, mainly narrowing of the joint space in more than two-thirds of the patients and ankylosis in almost 10% of the cases. Only CTJ space narrowing reached statistical significance compared with controls. More than one structural
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of diminished pitch range are the overall physical condition of the subject and the presence or absence of neurological diseases. Subjects in good physical condition have larger phonational ranges than those in poor condition as in patients with advanced RA as reported by R.J. Baken.21 The positioning of subject while the frequency range is being determined also plays a role. Both upper and lower fundamental frequency limits seem to be reduced in the supine position, with a consequent reduction in the pitch range. In our study the pitch range was determined while patients were in the sitting position. It is also worth noting that intrasubject variability by at least a few semitones has also been reported.22 Previous radiological study using low-voltage radiographic technique has shown changes in the CTJ as osseous destruction of the cricoid and/or inferior thyroid cornu at the joint in four out of 17 females.8 In our study, there were no signs of erosion or destruction of either the thyroid or cricoid cartilages. Another important radiological finding worth noting in our study is the presence of vocal fold thickening which can be explained by the endoscopic finding of vocal fold edema in roughly the same percentage of patients. The radiological vocal fold thickening can also be attributed to the virtual shortening of the vocal fold secondary to incomplete or inefficient lengthening. With respect to the acoustic analysis, most of the results were substantiated by the laryngeal findings and symptoms. The inflammation affecting the vocal folds can result in changes in the vocal fold behavior and an increase in the perturbation parameters. Cycle-to-cycle variation in pitch and intensity may be affected by changes in the consistency and thickness of the vocal fold as seen in our study. It is also worth noting the increase in F0 in females with RA (177.25 vs. 171.25 Hz in normals), even though it was not significant. This could be accounted for by the limitation in the movement of the vocal folds, as more than 90% and close to 50% of patients with RA had CTJ and CAJ involvement, respectively. The impaired mobility can lead to a decrease in the muscle mass with a resulting increase in frequency. This explanation remains hypothetical
TABLE 4. HRCT Findings Patients Control P (%) (%) Value
CT Findings Ankylosis CTJ Ankylosis CAJ Increase in the density of CTJ Increase in the density of CAJ Narrowing in CTJ space Narrowing in CAJ space Vocal fold thickening
9.1 0 45.5 9.1 81.8 45.5 27.3
0 0 12.5 12.5 0.0 12.5 0.0
0.381 0.228 0.127 0.811 0.000 0.127 0.107
abnormality was present in almost half of the subjects. Density changes together with either narrowing of the intercartilaginous space or ankylosis were present in five out of the nine subjects. It seems that CTJ is affected more commonly than the CAJ. Not all subjects who had a decrease in CTJ space had a decrease in CAJ space (only five out of nine), whereas all patients who had a decrease in CAJ space had a decrease in the CTJ space. With respect to density changes, the increase in density was also more pronounced in the CTJ compared with the CAJ. Not all patients who had an increase in CTJ density had an increase in CAJ density. Only one patient had an increase in CAJ density compared with five with respect to the CTJ. These findings can partially explain the decrease in pitch range and the loss of range reported in 45% of our patients. Clearly, the radiological changes of the CTJ may play a role but are not the major determinants of the vocal-range changes reported by patients with RA. The loss of range can be the result of a decrease in the agility and flexibility of the vocal folds or the variations in the airflow in relation to breathing support and control, which might be affected in patients with advanced RA. Pulmonary complications caused by RA are a clinically relevant aspect of this chronic arthropathy. Those complications can involve all parts of the thorax, including the lung parenchyma, the pleura, and the thoracic cage.19,20 Other causes
TABLE 5. Acoustic Analysis Patients (n ¼ 11)
Control (n ¼ 8)
Mean—Female (F0 ¼ 177.25) and Male (F0 ¼ 92.80)
SD
Mean—Female (F0 ¼ 171.25) and Male (F0 ¼ 99.42)
SD
P Value
F0 RAP Shimmer NHR VTI MPT
162.197 1.71 6.84 0.16 0.043 9.73
45.15 0.78 2.86 0.73 0.028 2.61
153.13 0.97 3.40 0.22 0.036 16.24
41.58 0.33 1.05 0.25 0.012 1.30
0.62 0.021 0.002 0.869 0.901 0.002
Habitual pitch Range of pith (Hz) Maximum (Hz) Minimum (Hz)
150.02 167.46 287.8 120.44
Acoustic Analysis
35.72 95.05 109.78 40.31
148.92 277.28 396.28 119
Abbreviation: SD, standard deviation; NHR, noise-to-harmonic ratio; VTI, Voice Turbulence Index; MPT, maximum phonation time.
43.70 100.28 70.76 34.85
0.869 0.029 0.018 0.934
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Cricothyroid Joint in Rheumatoid Arthritis
and needs further investigation. The lack of similar findings in male F0 could be attributed to the relatively small number of cases (only two), which prohibits us from drawing any conclusion. With respect to vocal-range changes, we compared in the RA group the pitch range and prevalence of loss of range in those with abnormal CTJ versus those with normal CTJ. Only one subject had normal CTJ on CT scan and the remaining 10 had either ankylosis or narrowing in the joint space. The patient with normal CTJ had no loss of range clinically, and the pitch range was 147.59 Hz, whereas 50% of the patients with abnormal CTJ had loss of range and the average pitch range was 169.45 Hz. No statistically significant conclusion can be drawn by comparing the pitch range in the two subgroups in view of the small number of cases (one vs. 10). Closer examination of the data reveals that the maximum pitch was lower in subjects with abnormal CTJ (284.47 vs. 321.9 Hz), probably indicating CTJ dysfunction. One of the major limitations of our study is the small number of cases and the fact that the radiological evaluation was performed when the vocal folds were not in the phonatory position, that is, the actual contraction of the cricothyroid muscle was not monitored or measured electromyographically or endoscopically. It is also worth mentioning the normal anatomical variation of the CTJ by site as described by Maue-Dickson et al in his cadaveric dissection report, over which we had no control or actual measure in our study.23 The variation by site plays a counterintuitive role in the association between the structural anomalies seen on CT scan and the functional limitations, namely the loss of range and reduced pitch range. Nevertheless, our study is the first study that investigates radiologically, using CT scan, the structural changes in the CTJ, and acoustically, the vocal range in subjects with advanced RA compared with controls. Definitely future investigations to further elucidate the aforementioned changes and their impact on daily life especially in professional voice users are warranted.
CONCLUSION In summary, this study demonstrates that the incidence of anatomical abnormalities in the CTJ using HRCT is higher in patients with RA compared with a matched control group. Patients also demonstrated functional abnormalities, namely a contracted vocal range, clinically and a decrease in the pitch range on acoustic analysis affecting mainly the high notes. The long-term consequences of the radiological abnormalities of the CTJ are not known. Both the speaking voice and the professional voice may suffer from these structural and functional abnormalities.
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