- Email: [email protected]
Structural and Anatomic Laryngeal Measurements in Geriatric Population Using MRI
ARTICLE IN PRESS Structural and Anatomic Laryngeal Measurements in Geriatric Population Using MRI *Georges Ziade, †Sahar Semaan, ‡Jana Ghulmiyyah, *Maher Kasti, and *Abdul Latif H. Hamdan, *†‡Beirut, Lebanon Summary: Objective. The study aims to evaluate the changes in volume and dimensions of the thyroarytenoid (TA) muscle in the elderly using magnetic resonance imaging (MRI). Study Design. This is a retrospective study. Methods. The neck MRIs of 40 adult patients aged less than 65 years old and 40 patients aged 65 years old and above were compared. Demographic data included age and gender. The length, width, and height of the TA muscle as well as its volume were measured on each side, right and left, in both groups. Results. The differences in the mean length, width, and height of TA muscle were not statistically significant between the two groups on either right or left side. Similarly, there was no statistically significant difference in the mean volume of the TA muscles between the two groups on either side as well. The mean volume of the right and left TA muscles in those aged less than 65 years was 0.65 ± 0.26 mL and 0.69 ± 0.30 mL, respectively. The mean volume of the right and left TA muscles in the elderly group was 0.72 ± 0.31 mL and 0.72 ± 0.32 mL, respectively. Conclusion. Using MRI, there are no dimensional or volumetric changes in TA muscles with aging. Key Words: Aging–Presbyphonia–Magnetic resonance imaging–Thyroarytenoid muscle–Vocal fold.
INTRODUCTION Presbyphonia is a term used to denote phonatory changes witnessed in the elderly. These include vocal roughness, vocal fatigue, tremor, and inability to project the voice.1,2 When present, presbyphonia is perceived as asthenic, breathy, and rough, and acoustically there is an increase in the perturbation parameters and noise-to-harmonic ratio with changes in vocal pitch, namely an increase in men and a decrease in women.3 Endoscopically, bowing of the membranous part of the vocal fold with incomplete closure could be present. A decrease in the mucosal wave amplitude and/or reduced phase of glottal closure may be seen on stroboscopy.4,5 Despite the ubiquity in reports on the perceptual, acoustic, and endoscopic findings in the elderly voice, few imaging studies have been reported. Laryngeal imaging includes ultrasound, plain radiography, computerized tomography (CT), and magnetic resonance imaging (MRI). Previously published imaging studies investigated the degree and patterns of ossification in the laryngeal cartilages. Yeager et al, using CT imaging, concluded that a reliable pattern of ossification could not be found in any of the thyroid, cricoid, and arytenoid cartilages. The authors concluded that patterns of laryngeal cartilages ossification do not correlate with aging.6 In another study by Fatterpekar et al, using MRI, differences in the signal of the thyroid, cricoid, and arytenoid cartilages were examined on T1-weighted images in 60 patients of different age groups. The authors reported the presence
Accepted for publication June 16, 2016. Conflict of interest: No conflict of interest or financial support in relation to this manuscript. From the *Department of Otolaryngology—Head & Neck Surgery, American University of Beirut Medical Center, Beirut, Lebanon; †Department of Clinical Radiology, American University of Beirut Medical Center, Beirut, Lebanon; and the ‡Faculty of Medicine, American University of Beirut, Beirut, Lebanon. Address correspondence and reprint requests to Abdul Latif H. Hamdan, Division of Laryngology, Director of Hamdan Voice Unit, Otolaryngology Head and Neck Surgery, American University of Beirut, Beirut, Lebanon. E-mail: [email protected] Journal of Voice, Vol. ■■, No. ■■, pp. ■■-■■ 0892-1997 © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jvoice.2016.06.008
of symmetrical ossification of laryngeal cartilages with age, as well as an increased high signal in all laryngeal cartilages.7 The scarcity of radiological reports on the laryngeal muscular changes witnessed in the elderly has intrigued the authors of this article to investigate radiologically the dimensional and volumetric changes of the thyroarytenoid (TA) muscles in the elderly compared with subjects below the age of 65 years. Given that MRI is superior to CT scan in detecting soft tissue changes in particular intra-laryngeal muscular changes,8,9 MRI was selected as the primary imaging modality in this investigation. The hypothesis is that a difference in TA muscle dimensions and volume is present on MRI between the different age groups. MATERIALS AND METHODS This is a retrospective study approved by the Institutional Review Board at the American University of Beirut Medical Center. The medical records of patients who underwent MRI of the neck between July 2010 and October 2015 at the radiology center were reviewed. Patients with known myopathy, vocal cord paralysis, laryngeal lesion, and history of laryngeal cancer, laryngeal surgery, or radiation were excluded. Neck MRIs of 4-mm slice thickness performed using a 3.0 Tesla Philips Ingenia (Andover, Massachusetts, US) machine were examined. Images distorted by motion or other types of artifact related to image acquisition were also excluded. A total of 80 patients were included. These were stratified into two groups, 40 patients below the age of 65 years and 40 patients above or aged 65 years. The age of 65 was used to separate the two groups based on its common use in defining elderly subjects.10 Both axial and coronal planes short tau inversion recovery images were examined to assess the dimensions and volumes of the right and left TA muscles. The TA muscle vertical height was measured from its superior to inferior edge using coronal images (Figure 1A). The anteroposterior length and width of the TA muscles were measured using axial images. The length was measured from the anterior commissure to the vocal process of the arytenoid cartilage, and the width of the TA muscles was
ARTICLE IN PRESS 2
Journal of Voice, Vol. ■■, No. ■■, 2016
RESULTS Demographic data In the group aged less than 65 years old, the mean age was 45.08 (standard deviation = 13.18), with an age range of 21–63 years old. Twenty patients were male and 20 were female. In the group aged more than or equal to 65 years old, the mean age was 72.85 (standard deviation = 6.86), with an age range of 65–89 years old. The numbers of male and female patients were, respectively, 18 and 22 (Table 1). FIGURE 1. (A) The height of the TA muscle measured from its superior to inferior edge (arrow). (B) The anteroposterior length of the TA muscle measured from the anterior commissure to the vocal process of the arytenoid cartilage (arrow). The width of the TA muscle measured at its mid-aspect from the medial to the lateral edge (arrowhead). TA, thyroarytenoid.
measured at the mid-aspect of the muscles by computing the distance between the medial and lateral edges (Figure 1B). The volume of each TA muscle was then calculated using the product of the above measurements. Both groups were compared with respect to demographic data and MRI findings using nonparametric tests. Differences were considered significant for P < 0.05. Further analysis was performed to investigate the association between each radiological outcome measure and age, which was taken as a continuous variable. The statistical analysis was performed using SPSS software 22nd edition (IBM Corp., Armonk, NY, US). TABLE 1. Demographic Data Variables
<65 Years
≥65 Years
Total sample N = 40 N = 40 Mean age (±SD) 45.08 (±13.18) 72.85 (±6.86) Gender Male 20 (50.0%) 18 (45%) Female 20 (50.0%) 22 (55%) * P value significant at <0.05. Abbreviation: SD, standard deviation.
P Value*
MRI parametrical results in the two age groups (less than and more or equal to 65 years) Length of the thyroarytenoid muscle The mean length of the right TA muscle was 2.07 ± 0.39 cm in the group aged less than 65 years old, compared with 2.13 ± 0.52 cm in the group aged more than 65 years old. At the level of the left vocal cord, the mean length of the TA muscle in the first and second group was, respectively, 2.1 ± 0.4 cm and 2.16 ± 0.53 cm. The differences between the first and second group were not statistically significant. Width of the thyroarytenoid muscle The mean width of the right TA muscle was 0.61 ± 0.11 cm in the group aged less than 65 years old and 0.65 ± 0.13 cm in the group aged more than 65 years old. The mean width of the left TA muscle was 0.62 ± 0.12 cm in the first group and 0.64 ± 0.13 in the second group. The differences in mean width were also not significant between the two groups (Table 2). Height of the thyroarytenoid muscle As for the height of the TA muscle, it was 1 ± 0.18 cm on the right side in both groups. On the left side, the height of the TA muscle was 1.02 ± 0.18 cm and 0.99 ± 0.18 cm, respectively, in the first and second group (Table 2). No significant difference in TA muscle height was found between the two groups.
0.65
Volume of the thyroarytenoid muscle The mean volume of the right TA muscle in the first and second group was, respectively, 0.65 ± 0.26 mL and 0.72 ± 0.31 mL. As
TABLE 2. Right and Left Thyroarytenoid Muscle Dimensions and Volume in Both Groups Variable Right
Left
* P value significant at <0.05.
Length (cm) Width (cm) Height (cm) Volume (mL) Length (cm) Width (cm) Height (cm) Volume (mL)
Age <65 (N = 40)
Age ≥65 (N = 40)
P Value*
2.07 ± 0.39 0.61 ± 0.11 1.00 ± 0.18 0.65 ± 0.26 2.10 ± 0.40 0.62 ± 0.12 1.02 ± 0.18 0.69 ± 0.30
2.13 ± 0.52 0.65 ± 0.13 1.00 ± 0.18 0.72 ± 0.31 2.16 ± 0.53 0.64 ± 0.13 0.99 ± 0.18 0.72 ± 0.32
0.57 0.12 0.87 0.44 0.58 0.37 0.51 0.76
ARTICLE IN PRESS Georges Ziade et al
Laryngeal Measurements in Geriatric Population Using MRI
for the left TA muscle, the mean volume in the first and second group was, respectively, 0.69 ± 0.30 mL and 0.72 ± 0.32 mL. A slight increase in volume was present with age but did not reach statistical significance (Table 2). MRI parametrical results with age as continuous variable None of the dimensional measures, length, width, and height reached statistical significance when age was taken as a continuous variable. Similar results were found with respect to volumetric measures, with no statistical difference (P > 0.05). DISCUSSION The variations in skeletal muscles with age have been primarily attributed to many structural and physiological changes. At the neuromuscular junction, there is a reduction in the axon terminal area and changes in synaptic architecture, with primarily an increase in postsynaptic acetylcholine receptors’ surfaces.11 At the metabolic level, an increase in mitochondrial abnormalities is seen with a decrease in mitochondrial density and productivity.12 In parallel with these cellular changes, there is narrowing of the capillaries and vessels along with an alteration of their capacity to vasodilate, all of which leading to morphologic and functional changes.13 As a sequel, there is a loss of type I and type II muscular fibers with subsequent decrease in the overall muscle mass, speed, and force of contraction.14,15 This latter has also been attributed to hormonal changes as well as connective tissue infiltration leading to changes in muscular consistency, volume, and overall function.14 As the larynx is a musculoskeletal organ and a hormonal target, it is also affected with aging by all the aforementioned changes in parallel with a decrease in the number of sex hormone receptors.16 Morphologically, there is reduction in muscle mass, loss of muscle fibers type I and/or II, and change in the connective tissue pattern.17,18 At the metabolic level, there is an increased rate of mitochondrial mutations and abnormal accumulations of mitochondria, with a subsequent reduction in speed and force of contraction.19 Also, with age, a reduced blood flow and capillary surface area at the muscular level leads to a decrease in oxygen and nutrient supply, along with a reduced ability to eliminate cellular waste products.11,20 Subsequently, all the laryngeal structures including the TA muscles are affected, with potential morphologic and metabolic alterations possibly leading to changes in muscle mass and voice quality.3,11 Based on a review of the English literature, no previous radiological study using MRI has investigated these potential changes of the intrinsic laryngeal muscles except for one study that evaluated age-related signal patterns of the thyroid, cricoid, and arytenoid cartilages. The results indicated that laryngeal cartilages ossify symmetrically and the imaging signal on MRI increases with age among all laryngeal cartilages.7 There was no mentioning of the possible volumetric changes of the intrinsic laryngeal muscles despite the importance of identifying these changes for better assessment and treatment of presbyphonia. Based on the results of this investigation, no significant volumetric or dimensional differences in the TA muscles were found
3
between the two studied groups. The absence of significant differences between the two groups can be explained hypothetically by the possible lack of correlation between the possible histologic changes that might affect the senile TA muscle and its overall volume and dimensions. Although it remains a musculoskeletal structure, the TA muscle aging process seems to be different compared with other skeletal muscles.11,21 Senile body skeletal muscles undergo a decrease in muscle mass with loss and decrease in volume of both muscular fibers types I and II.14,22 On the other hand, the change in the TA muscular fibers is a point of controversy. The patterns of quantitative and qualitative fiber changes in the TA muscle are different compared with other limb skeletal muscles. Kersing and Jennekens reported only loss of type I fibers.23 In contrast, Malmgren et al reported only loss of type II fibers.21 Sato and Tauchi studied 109 larynges of different ages and looked into the histopathologic changes affecting the TA muscle with time. They reported loss of both types I and II fibers with age but with an increase in the volume of each fiber type that is more pronounced in type I fibers.24 Malmgren et al studied 28 larynxes aged 26–97 years old, and their results indicated a selective loss of type I fibers with age, but they also reported a trend toward compensation hypertrophy of the remaining type I fibers.21 The latter may explain the persistence in volume despite the loss of different types of fibers within the TA muscles. Furthermore, with aging, the TA muscle volume is not only dependent on changes in muscle fibers but also on connective tissue changes. In the senile larynx, muscular fibers are replaced by collagen fibers concomitantly with an increase in collagenous fibers and a decrease in the reticular fibers of the lamina propria.25,26 The amount of collagen fibers increases mainly in the endomysial spaces of the TA muscle replacing atrophic muscular fibers.20,23 Another feature of the senile TA muscle is the increased ragged red fibers as a result of aggregations of mitochondria and increased mitochondrial activity within the subsarcolemmal regions of the muscle.23,27 Ragged red fibers are more abundant in a senile TA muscle compared with limb skeletal muscles.23 Being essential elements that affect muscular volume,28 their increase with age accounting for a relatively bigger part of TA muscle volume can explain the lack of volume changes with age. This study is the first to examine dimensional and volumetric changes in TA muscles in the elderly compared with subjects aged less than 65 years old. Nevertheless, it carries few limitations that can be areas of focus for future research projects. One is the nature of this investigation, namely being retrospective which hinders the ability to ask patients about their phonatory behavior, which can affect the degree of muscle atrophy. Second is the absence of indirect laryngeal examination that would have been of added value to this study in order to exclude vocal fold paralysis, paresis, or lesions, and to draw any possible clinical significance. Third is the presence of systemic diseases such as glycogen storage diseases and connective tissue diseases, which may cause substance deposits within the TA muscle and affect its overall volume. Fourth is the use of a single measurement in each TA muscle dimension, which limits the accurate threedimensional volumetric calculation.
ARTICLE IN PRESS 4 CONCLUSIONS This is the first study to assess the volumetric and dimensional changes of the TA muscle in the elderly using MRI. The results showed no significant difference in any TA measure compared with subjects below the age of 65 years. Although histologic changes with aging do affect the TA muscles as previously reported, there are no concomitant volumetric changes. REFERENCES 1. Gregory ND, Chandran S, Lurie D, et al. Voice disorders in the elderly. J Voice. 2012;26:254–258. 2. Kendall K. Presbyphonia: a review. Curr Opin Otolaryngol Head Neck Surg. 2007;15:137–140. 3. Honjo I, Isshiki N. Laryngoscopic and voice characteristics of aged persons. Arch Otolaryngol. 1980;106:149–150. 4. Martins RH, Gonçalvez TM, Pessin AB, et al. Aging voice: presbyphonia. Aging Clin Exp Res. 2014;26:1–5. 5. Pontes P, Yamasaki R, Behlau M. Morphological and functional aspects of the senile larynx. Folia Phoniatr Logop. 2006;58:151–158. 6. Yeager VL, Lawson C, Archer CR. Ossification of the laryngeal cartilages as it relates to computed tomography. Invest Radiol. 1982;17:11–19. 7. Fatterpekar GM, Mukherji SK, Rajgopalan P, et al. Normal age-related signal change in the laryngeal cartilages. Neuroradiology. 2004;46:678–681. 8. Yamasaki R, Behlau M, do Brasil Ode O, et al. MRI anatomical and morphological differences in the vocal tract between dysphonic and normal adult women. J Voice. 2011;25:743–750. 9. Maroldi R, Ravanelli M, Farina D. Magnetic resonance for laryngeal cancer. Curr Opin Otolaryngol Head Neck Surg. 2014;22:131–139. 10. WHO. World Health Organisation. Definition of an Older or Elderly Person. Geneva, Switzerland: 2010. 11. Thomas LB, Harrison AL, Stemple JC. Aging thyroarytenoid and limb skeletal muscle: lessons in contrast. J Voice. 2008;22:430–450. 12. Wanagat J, Cao Z, Pathare P,et al. Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia. FASEB J. 2001;15:322–332. 13. Bearden SE. Effect of aging on the structure and function of skeletal muscle microvascular networks. Microcirculation. 2006;13:279–288.
Journal of Voice, Vol. ■■, No. ■■, 2016 14. Lexell J, Henriksson-Larsén K, Winblad B, et al. Distribution of different fiber types in human skeletal muscles: effects of aging studied in whole muscle cross sections. Muscle Nerve. 1983;6:588–595. 15. Larsson L. Motor units: remodeling in aged animals. J Gerontol A Biol Sci Med Sci. 1995;50 Spec No:91–95. 16. Newman SR, Butler J, Hammond EH, et al. Preliminary report on hormone receptors in the human vocal fold. J Voice. 2000;14:72–81. 17. Segre R. Senescence of the voice. Eye Ear Nose Throat Mon. 1971;50:223– 227. 18. Lynch NA, Metter EJ, Lindle RS, et al. Muscle quality. I. Age-associated differences between arm and leg muscle groups. J Appl Physiol. 1999;86: 188–194. 19. McMullen CA, Andrade FH. Contractile dysfunction and altered metabolic profile of the aging rat thyroarytenoid muscle. J Appl Physiol. 2006;100: 602–608. 20. Rodeno MT, Sanchez-Fernandez JM, Rivera-Pomar JM. Histochemical and morphometrical ageing changes in human vocal cord muscles. Acta Otolaryngol. 1993;113:445–449. 21. Malmgren LT, Fisher PJ, Bookman LM, et al. Age-related changes in muscle fiber types in the human thyroarytenoid muscle: an immunohistochemical and stereological study using confocal laser scanning microscopy. Otolaryngol Head Neck Surg. 1999;121:441–451. 22. Lexell J, Downham D, Sjostrom M. Distribution of different fibre types in human skeletal muscles. Fibre type arrangement in m. vastus lateralis from three groups of healthy men between 15 and 83 years. J Neurol Sci. 1986;72:211–222. 23. Kersing W, Jennekens FG. Age-related changes in human thyroarytenoid muscles: a histological and histochemical study. Eur Arch Otorhinolaryngol. 2004;261:386–392. 24. Sato T, Tauchi H. Age changes in human vocal muscle. Mech Ageing Dev. 1982;18:67–74. 25. Baken RJ. The aged voice: a new hypothesis. J Voice. 2005;19:317–325. 26. Sato K, Hirano M, Nakashima T. Age-related changes of collagenous fibers in the human vocal fold mucosa. Ann Otol Rhinol Laryngol. 2002;111:15–20. 27. Rosenfield DB, Miller RH, Sessions RB, et al. Morphologic and histochemical characteristics of laryngeal muscle. Arch Otolaryngol. 1982;108:662–666. 28. Dalakas MC, Illa I, Pezeshkpour GH, et al. Mitochondrial myopathy caused by long-term zidovudine therapy. N Engl J Med. 1990;322:1098–1105.
INTRODUCTION Presbyphonia is a term used to denote phonatory changes witnessed in the elderly. These include vocal roughness, vocal fatigue, tremor, and inability to project the voice.1,2 When present, presbyphonia is perceived as asthenic, breathy, and rough, and acoustically there is an increase in the perturbation parameters and noise-to-harmonic ratio with changes in vocal pitch, namely an increase in men and a decrease in women.3 Endoscopically, bowing of the membranous part of the vocal fold with incomplete closure could be present. A decrease in the mucosal wave amplitude and/or reduced phase of glottal closure may be seen on stroboscopy.4,5 Despite the ubiquity in reports on the perceptual, acoustic, and endoscopic findings in the elderly voice, few imaging studies have been reported. Laryngeal imaging includes ultrasound, plain radiography, computerized tomography (CT), and magnetic resonance imaging (MRI). Previously published imaging studies investigated the degree and patterns of ossification in the laryngeal cartilages. Yeager et al, using CT imaging, concluded that a reliable pattern of ossification could not be found in any of the thyroid, cricoid, and arytenoid cartilages. The authors concluded that patterns of laryngeal cartilages ossification do not correlate with aging.6 In another study by Fatterpekar et al, using MRI, differences in the signal of the thyroid, cricoid, and arytenoid cartilages were examined on T1-weighted images in 60 patients of different age groups. The authors reported the presence
Accepted for publication June 16, 2016. Conflict of interest: No conflict of interest or financial support in relation to this manuscript. From the *Department of Otolaryngology—Head & Neck Surgery, American University of Beirut Medical Center, Beirut, Lebanon; †Department of Clinical Radiology, American University of Beirut Medical Center, Beirut, Lebanon; and the ‡Faculty of Medicine, American University of Beirut, Beirut, Lebanon. Address correspondence and reprint requests to Abdul Latif H. Hamdan, Division of Laryngology, Director of Hamdan Voice Unit, Otolaryngology Head and Neck Surgery, American University of Beirut, Beirut, Lebanon. E-mail: [email protected] Journal of Voice, Vol. ■■, No. ■■, pp. ■■-■■ 0892-1997 © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jvoice.2016.06.008
of symmetrical ossification of laryngeal cartilages with age, as well as an increased high signal in all laryngeal cartilages.7 The scarcity of radiological reports on the laryngeal muscular changes witnessed in the elderly has intrigued the authors of this article to investigate radiologically the dimensional and volumetric changes of the thyroarytenoid (TA) muscles in the elderly compared with subjects below the age of 65 years. Given that MRI is superior to CT scan in detecting soft tissue changes in particular intra-laryngeal muscular changes,8,9 MRI was selected as the primary imaging modality in this investigation. The hypothesis is that a difference in TA muscle dimensions and volume is present on MRI between the different age groups. MATERIALS AND METHODS This is a retrospective study approved by the Institutional Review Board at the American University of Beirut Medical Center. The medical records of patients who underwent MRI of the neck between July 2010 and October 2015 at the radiology center were reviewed. Patients with known myopathy, vocal cord paralysis, laryngeal lesion, and history of laryngeal cancer, laryngeal surgery, or radiation were excluded. Neck MRIs of 4-mm slice thickness performed using a 3.0 Tesla Philips Ingenia (Andover, Massachusetts, US) machine were examined. Images distorted by motion or other types of artifact related to image acquisition were also excluded. A total of 80 patients were included. These were stratified into two groups, 40 patients below the age of 65 years and 40 patients above or aged 65 years. The age of 65 was used to separate the two groups based on its common use in defining elderly subjects.10 Both axial and coronal planes short tau inversion recovery images were examined to assess the dimensions and volumes of the right and left TA muscles. The TA muscle vertical height was measured from its superior to inferior edge using coronal images (Figure 1A). The anteroposterior length and width of the TA muscles were measured using axial images. The length was measured from the anterior commissure to the vocal process of the arytenoid cartilage, and the width of the TA muscles was
ARTICLE IN PRESS 2
Journal of Voice, Vol. ■■, No. ■■, 2016
RESULTS Demographic data In the group aged less than 65 years old, the mean age was 45.08 (standard deviation = 13.18), with an age range of 21–63 years old. Twenty patients were male and 20 were female. In the group aged more than or equal to 65 years old, the mean age was 72.85 (standard deviation = 6.86), with an age range of 65–89 years old. The numbers of male and female patients were, respectively, 18 and 22 (Table 1). FIGURE 1. (A) The height of the TA muscle measured from its superior to inferior edge (arrow). (B) The anteroposterior length of the TA muscle measured from the anterior commissure to the vocal process of the arytenoid cartilage (arrow). The width of the TA muscle measured at its mid-aspect from the medial to the lateral edge (arrowhead). TA, thyroarytenoid.
measured at the mid-aspect of the muscles by computing the distance between the medial and lateral edges (Figure 1B). The volume of each TA muscle was then calculated using the product of the above measurements. Both groups were compared with respect to demographic data and MRI findings using nonparametric tests. Differences were considered significant for P < 0.05. Further analysis was performed to investigate the association between each radiological outcome measure and age, which was taken as a continuous variable. The statistical analysis was performed using SPSS software 22nd edition (IBM Corp., Armonk, NY, US). TABLE 1. Demographic Data Variables
<65 Years
≥65 Years
Total sample N = 40 N = 40 Mean age (±SD) 45.08 (±13.18) 72.85 (±6.86) Gender Male 20 (50.0%) 18 (45%) Female 20 (50.0%) 22 (55%) * P value significant at <0.05. Abbreviation: SD, standard deviation.
P Value*
MRI parametrical results in the two age groups (less than and more or equal to 65 years) Length of the thyroarytenoid muscle The mean length of the right TA muscle was 2.07 ± 0.39 cm in the group aged less than 65 years old, compared with 2.13 ± 0.52 cm in the group aged more than 65 years old. At the level of the left vocal cord, the mean length of the TA muscle in the first and second group was, respectively, 2.1 ± 0.4 cm and 2.16 ± 0.53 cm. The differences between the first and second group were not statistically significant. Width of the thyroarytenoid muscle The mean width of the right TA muscle was 0.61 ± 0.11 cm in the group aged less than 65 years old and 0.65 ± 0.13 cm in the group aged more than 65 years old. The mean width of the left TA muscle was 0.62 ± 0.12 cm in the first group and 0.64 ± 0.13 in the second group. The differences in mean width were also not significant between the two groups (Table 2). Height of the thyroarytenoid muscle As for the height of the TA muscle, it was 1 ± 0.18 cm on the right side in both groups. On the left side, the height of the TA muscle was 1.02 ± 0.18 cm and 0.99 ± 0.18 cm, respectively, in the first and second group (Table 2). No significant difference in TA muscle height was found between the two groups.
0.65
Volume of the thyroarytenoid muscle The mean volume of the right TA muscle in the first and second group was, respectively, 0.65 ± 0.26 mL and 0.72 ± 0.31 mL. As
TABLE 2. Right and Left Thyroarytenoid Muscle Dimensions and Volume in Both Groups Variable Right
Left
* P value significant at <0.05.
Length (cm) Width (cm) Height (cm) Volume (mL) Length (cm) Width (cm) Height (cm) Volume (mL)
Age <65 (N = 40)
Age ≥65 (N = 40)
P Value*
2.07 ± 0.39 0.61 ± 0.11 1.00 ± 0.18 0.65 ± 0.26 2.10 ± 0.40 0.62 ± 0.12 1.02 ± 0.18 0.69 ± 0.30
2.13 ± 0.52 0.65 ± 0.13 1.00 ± 0.18 0.72 ± 0.31 2.16 ± 0.53 0.64 ± 0.13 0.99 ± 0.18 0.72 ± 0.32
0.57 0.12 0.87 0.44 0.58 0.37 0.51 0.76
ARTICLE IN PRESS Georges Ziade et al
Laryngeal Measurements in Geriatric Population Using MRI
for the left TA muscle, the mean volume in the first and second group was, respectively, 0.69 ± 0.30 mL and 0.72 ± 0.32 mL. A slight increase in volume was present with age but did not reach statistical significance (Table 2). MRI parametrical results with age as continuous variable None of the dimensional measures, length, width, and height reached statistical significance when age was taken as a continuous variable. Similar results were found with respect to volumetric measures, with no statistical difference (P > 0.05). DISCUSSION The variations in skeletal muscles with age have been primarily attributed to many structural and physiological changes. At the neuromuscular junction, there is a reduction in the axon terminal area and changes in synaptic architecture, with primarily an increase in postsynaptic acetylcholine receptors’ surfaces.11 At the metabolic level, an increase in mitochondrial abnormalities is seen with a decrease in mitochondrial density and productivity.12 In parallel with these cellular changes, there is narrowing of the capillaries and vessels along with an alteration of their capacity to vasodilate, all of which leading to morphologic and functional changes.13 As a sequel, there is a loss of type I and type II muscular fibers with subsequent decrease in the overall muscle mass, speed, and force of contraction.14,15 This latter has also been attributed to hormonal changes as well as connective tissue infiltration leading to changes in muscular consistency, volume, and overall function.14 As the larynx is a musculoskeletal organ and a hormonal target, it is also affected with aging by all the aforementioned changes in parallel with a decrease in the number of sex hormone receptors.16 Morphologically, there is reduction in muscle mass, loss of muscle fibers type I and/or II, and change in the connective tissue pattern.17,18 At the metabolic level, there is an increased rate of mitochondrial mutations and abnormal accumulations of mitochondria, with a subsequent reduction in speed and force of contraction.19 Also, with age, a reduced blood flow and capillary surface area at the muscular level leads to a decrease in oxygen and nutrient supply, along with a reduced ability to eliminate cellular waste products.11,20 Subsequently, all the laryngeal structures including the TA muscles are affected, with potential morphologic and metabolic alterations possibly leading to changes in muscle mass and voice quality.3,11 Based on a review of the English literature, no previous radiological study using MRI has investigated these potential changes of the intrinsic laryngeal muscles except for one study that evaluated age-related signal patterns of the thyroid, cricoid, and arytenoid cartilages. The results indicated that laryngeal cartilages ossify symmetrically and the imaging signal on MRI increases with age among all laryngeal cartilages.7 There was no mentioning of the possible volumetric changes of the intrinsic laryngeal muscles despite the importance of identifying these changes for better assessment and treatment of presbyphonia. Based on the results of this investigation, no significant volumetric or dimensional differences in the TA muscles were found
3
between the two studied groups. The absence of significant differences between the two groups can be explained hypothetically by the possible lack of correlation between the possible histologic changes that might affect the senile TA muscle and its overall volume and dimensions. Although it remains a musculoskeletal structure, the TA muscle aging process seems to be different compared with other skeletal muscles.11,21 Senile body skeletal muscles undergo a decrease in muscle mass with loss and decrease in volume of both muscular fibers types I and II.14,22 On the other hand, the change in the TA muscular fibers is a point of controversy. The patterns of quantitative and qualitative fiber changes in the TA muscle are different compared with other limb skeletal muscles. Kersing and Jennekens reported only loss of type I fibers.23 In contrast, Malmgren et al reported only loss of type II fibers.21 Sato and Tauchi studied 109 larynges of different ages and looked into the histopathologic changes affecting the TA muscle with time. They reported loss of both types I and II fibers with age but with an increase in the volume of each fiber type that is more pronounced in type I fibers.24 Malmgren et al studied 28 larynxes aged 26–97 years old, and their results indicated a selective loss of type I fibers with age, but they also reported a trend toward compensation hypertrophy of the remaining type I fibers.21 The latter may explain the persistence in volume despite the loss of different types of fibers within the TA muscles. Furthermore, with aging, the TA muscle volume is not only dependent on changes in muscle fibers but also on connective tissue changes. In the senile larynx, muscular fibers are replaced by collagen fibers concomitantly with an increase in collagenous fibers and a decrease in the reticular fibers of the lamina propria.25,26 The amount of collagen fibers increases mainly in the endomysial spaces of the TA muscle replacing atrophic muscular fibers.20,23 Another feature of the senile TA muscle is the increased ragged red fibers as a result of aggregations of mitochondria and increased mitochondrial activity within the subsarcolemmal regions of the muscle.23,27 Ragged red fibers are more abundant in a senile TA muscle compared with limb skeletal muscles.23 Being essential elements that affect muscular volume,28 their increase with age accounting for a relatively bigger part of TA muscle volume can explain the lack of volume changes with age. This study is the first to examine dimensional and volumetric changes in TA muscles in the elderly compared with subjects aged less than 65 years old. Nevertheless, it carries few limitations that can be areas of focus for future research projects. One is the nature of this investigation, namely being retrospective which hinders the ability to ask patients about their phonatory behavior, which can affect the degree of muscle atrophy. Second is the absence of indirect laryngeal examination that would have been of added value to this study in order to exclude vocal fold paralysis, paresis, or lesions, and to draw any possible clinical significance. Third is the presence of systemic diseases such as glycogen storage diseases and connective tissue diseases, which may cause substance deposits within the TA muscle and affect its overall volume. Fourth is the use of a single measurement in each TA muscle dimension, which limits the accurate threedimensional volumetric calculation.
ARTICLE IN PRESS 4 CONCLUSIONS This is the first study to assess the volumetric and dimensional changes of the TA muscle in the elderly using MRI. The results showed no significant difference in any TA measure compared with subjects below the age of 65 years. Although histologic changes with aging do affect the TA muscles as previously reported, there are no concomitant volumetric changes. REFERENCES 1. Gregory ND, Chandran S, Lurie D, et al. Voice disorders in the elderly. J Voice. 2012;26:254–258. 2. Kendall K. Presbyphonia: a review. Curr Opin Otolaryngol Head Neck Surg. 2007;15:137–140. 3. Honjo I, Isshiki N. Laryngoscopic and voice characteristics of aged persons. Arch Otolaryngol. 1980;106:149–150. 4. Martins RH, Gonçalvez TM, Pessin AB, et al. Aging voice: presbyphonia. Aging Clin Exp Res. 2014;26:1–5. 5. Pontes P, Yamasaki R, Behlau M. Morphological and functional aspects of the senile larynx. Folia Phoniatr Logop. 2006;58:151–158. 6. Yeager VL, Lawson C, Archer CR. Ossification of the laryngeal cartilages as it relates to computed tomography. Invest Radiol. 1982;17:11–19. 7. Fatterpekar GM, Mukherji SK, Rajgopalan P, et al. Normal age-related signal change in the laryngeal cartilages. Neuroradiology. 2004;46:678–681. 8. Yamasaki R, Behlau M, do Brasil Ode O, et al. MRI anatomical and morphological differences in the vocal tract between dysphonic and normal adult women. J Voice. 2011;25:743–750. 9. Maroldi R, Ravanelli M, Farina D. Magnetic resonance for laryngeal cancer. Curr Opin Otolaryngol Head Neck Surg. 2014;22:131–139. 10. WHO. World Health Organisation. Definition of an Older or Elderly Person. Geneva, Switzerland: 2010. 11. Thomas LB, Harrison AL, Stemple JC. Aging thyroarytenoid and limb skeletal muscle: lessons in contrast. J Voice. 2008;22:430–450. 12. Wanagat J, Cao Z, Pathare P,et al. Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia. FASEB J. 2001;15:322–332. 13. Bearden SE. Effect of aging on the structure and function of skeletal muscle microvascular networks. Microcirculation. 2006;13:279–288.
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