Neurol Sci DOI 10.1007/s10072-015-2239-5
ORIGINAL ARTICLE
Spasmodic dysphonia follow-up with videolaryngoscopy and voice spectrography during treatment with botulinum toxin Marcello Esposito1 • R. Dubbioso1 • P. Apisa2 • R. Allocca1 • L. Santoro1 U. Cesari2
•
Received: 10 February 2015 / Accepted: 3 May 2015 Ó Springer-Verlag Italia 2015
Abstract Spasmodic dysphonia (SD) is a focal dystonia of laryngeal muscles seriously impairing quality of voice. Adductor SD (ADSD) is the most common presentation of this disorder that can be identified by specialized phoniatricians and neurologists firstly on a clinical evaluation and then confirmed by videolaryngoscopy (VL). Botulinum toxin (BTX) injection with electromyographic guidance in muscles around vocal cords is the most effective treatment. Voice Handicap Index (VHI) questionnaire is the main tool to assess dysphonia and response to treatment. Objective of this study is to perform VL and voice spectrography (VS) to confirm the efficacy of BTX injections over time. 13 patients with ADSD were studied with VHI, VL and VS before and after 4 consecutive treatment with onobotulinumtoxin-A. For each treatment vocal improvement was proved by a significant reduction of VHI score and increase of maximum time phonation and harmonic-tonoise ratio while VL showed the absence of spasm in most of patients. No change of the response to BTX was found between injections. This study supports the efficacy of the treatment of SD with BTX with objective measurements and suggests that the efficacy of recurring treatments is stable over time. Keywords Spasmodic dysphonia Dystonia Botulinum toxin Videolaryngoscopy Voice spectrography
& Marcello Esposito [email protected] 1
Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Via Sergio Pansini, 5, 80131 Naples, Italy
2
Otorhinolaryngology Department, University Federico II of Naples, Naples, Italy
Introduction Spasmodic dysphonia (SD) is a focal dystonia of vocal cords that occasionally is part of a wider neurologic disease or generalized dystonic syndrome, but it usually occurs as isolated disorder in adults [1]. SD presents two main phenotypes on the basis of the abnormal deviation of vocal cords in adduction or in abduction as result of excessive contraction of laryngeal muscles. Adductor SD (ADSD) is the most frequent type and it produces a strangulated quality of voice. ADSD is primarily diagnosed on clinical evaluation that is confirmed by the evidence of excessive spasmodic adduction of false vocal cords on videolaryngoscopy (VL) [2]. Voice spectrography (VS) gives further information on sound alteration, but does not provide specific diagnostic evidences [3]. The most effective treatment of ADSD is botulinum toxin (BTX) injection in thyroarytenoid muscles producing muscle relaxation and reducing excessive adduction of vocal cords. VL can show these changes after BTX injection AND can provide mainly qualitative data of BTX effects in SD while VS can produce quantitative measures including the maximum time phonation (MPT) and harmonic-to-noise ratio (HNR) that are often used in phonetics assessment. MTP is obtained during sustained vowel /a/ after a deep inspiration and normal duration is longer than 18 s. HNR defines the ratio between sound and noise in voice spectrum during spontaneous speech. An outstanding normal voice in silent room at medium intensity should have an HNR score higher than 13 dB [4]. MPT and HNR are reduced in SD and can be increased by BTX action on vocal cords. Clinical benefits from the treatment of SD with BTX occur few days after the injection and last 4–6 months, only minor side effects are reported occasionally [5]. The most used tool to evaluate clinical effectiveness of the treatment
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Neurol Sci
is the Voice Handicap Index (VHI) that is a questionnaire assessing the functional, emotional, and psychosocial consequences of voice disorders [6]. Reduction of the VHI score after BTX injection in muscles around vocal cords proved the efficacy of this treatment in few studies only on a clinical level but it did not give information on vocal alterations and abnormal contractures of vocal cords. On this background, we aimed to confirm the efficacy of BTX injections for ADSD and especially to evaluate the response of the treatment over time with the use of qualitative and quantitative measure of human voice with VS and VL in addition to clinical features reported by the VHI questionnaire.
Patients and methods 13 consecutive patients with ADSD never treated before with BTX were studied from 2012 to 2014. ADSD was diagnosed on the basis of clinical evaluation performed by a neurologist and a phoniatrician with expertise in dystonia and confirmed with VL showing spasmodic movements in adduction of vocal cords. Each patient received BTX injections in thyroarytenoid muscle in both sides with the aid of EMG guidance. Injections were performed by the phoniatrician supported by a neurophysiologist for the interpretation of EMG recordings. BTX used for the study was onabotulinumtoxin-A with a minimum dose of 2.5 U per vocal cord increasing the dose in case of unsatisfactory response (VHI [ 80). VHI, VS and VL were assessed before the injection and 2 weeks after for 4 consecutive treatments performed every 5 months. VS was recorded during a sustained vowel /a/ followed by pronunciation of an eight-word sentence and MPT and HNR and were obtained from each test. The phoniatrician performed the VL and rated for each patient the reduction or the full absence of spasmodic contraction of false vocal cords.
Results 13 patients (3 M, 10 F) with age ranging from 32 to 73 years (mean age 61 ± 15.8 years) and mean disease duration of 7.6 ± 4.4 years. The dose of onabotulinumtoxin-A given at the first injection was 2.5 U and the mean dose injected in following treatments was 3.26 ± 0.78. The mean score of VHI before each treatment was: 82.0 ± 7.72 (1st injection), 81.8 ± 7.23 (2nd injection), 81.1 ± 3.70 (3rd injection) and 81.2 ± 7.05 (4th injection). After BTX injection the score was: 66.38 ± 3.88 (1st injection), 65.69 ± 3.71 (2nd injection), 65.85 ± 4.63 (3rd injection) and 64.92 ± 4.72 (4th injection). The VHI score reduced significantly after treatment (p \ 0.001, Kruskal–Wallis test). These results were confirmed by Wilcoxon signed rank test, putting forward a significant improvement of VHI score but only after each treatment (p \ 0.001), with no significant effect over time (p [ 0.09) (Fig. 1).The mean duration (s) of MPT before each treatment was: 3.41 s ± 1.18 (1st injection), 3.54 s ± 1.22 (2 injection), 3.62 s ± 1.10 (3rd injection) and 3.62 s ± 1.19 (4th injection). The mean duration of MPT after each treatment was: 10.3 s ± 1.38 (1st injection), 11.5 s ± 1.10 (2nd injection), 12.8 s ± 1.26 (3rd injection) and 13.8 s ± 1.64 (4th injection). The MPT duration improved significantly after treatment (p \ 0.001, Kruskal–Wallis test). These results were confirmed by Wilcoxon signed rank test, putting forward a significant improvement of MPT duration after each treatment (p \ 0.001) and with no significant effect over time (p \ 0.03) (Fig. 2). The mean value of HNR before each treatment was: -3.08 dB ± 1.19 (1st injection), -2.73 dB ± 1.05 (2 injection), -2.80 dB ± 0.76 (3rd injection) and -1.71 dB ± 1.14 (4th injection). The mean value of HNR after each treatment was: 2.07 dB ± 1.02 (1st injection), 2.26 dB ± 1.03 (2nd injection), 2.16 dB ± 0.96 (3rd injection) and 2.03 dB ± 0.94 (4th injection).The HNR ratio improved
Statistical analysis Given the small number of subjects and because the distribution of variables could not be assumed to be approximately normal, all statistical analyses applied were nonparametric tests. The effects of BoNT on the outcome measures (MPT and VHI) were compared by means of the Kruskal–Wallis test. Moreover, we used Wilcoxon signed rank test to evaluate the benefit from BoNT-A injections after each injection and over time. Data were analyzed using software (SPSS v. 19.0 for Windows; SPSS Inc.). The significance level was set as p \ 0.05. Alpha inflation due to multiple comparisons was controlled according Bonferroni’s approach when appropriate. Data are presented as mean ± SD.
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Fig. 1 Effect of BTX injections on VHI score: VHI score reduces significantly after each injection (p \ 0.008)
Neurol Sci
Fig. 2 Effect of BTX injections on MPT. MPT duration increases significantly after each injection (p \ 0.008)
Fig. 3 Effect of BoNT-A injections on HNR. HNR level increases significantly after each injection (p \ 0.02)
significantly after treatment (p \ 0.001, Kruskal–Wallis test). These results were confirmed by Wilcoxon signed rank test, putting forward a significant improvement of HNR only after each treatment (p \ 0.024), with no significant effect over time (p [ 0.96); p values is \0.05 after Bonferroni’s correction for multiple comparisons (Fig. 3). VL showed the presence of false vocal cords spasms in all patients before each treatment (100 %) while the full absence of spasmodic contraction was observed in 53 % of cases (7/13) after the first injection, in 69 % (9/13) after the second injection, in 61 % (8/13) after the third injection and 69 % (9/13) after the fourth injection.
ADSD as VL can disclose abnormal mobility of vocal cords related to different disorders while VS can give more details on the level of vocal impairment [6]. Treatment of ADSD with BTX is proved to be effective mainly on a clinical level on the basis of VHI score and aim of this study was to provide instrumental evidence of persistent benefit from BTX injections over time. After the treatment in all patients spectography showed a prolonged duration of MTP and higher level of HNR [7, 8]. Our study confirmed a significant reduction of VHI score and VS showed significant changes after each injection with quantitative measures. The duration of the MTP and the level of HNR were increased after every treatment and there was no significant difference between each of them. VL cannot provide quantitative measures comparable during the follow-up and the rating from the examiner can be considered mainly as qualitative data correlating with results obtained with VS and VHI questionnaire. With VL the phoniatrician found almost a complete reduction of muscle spasms around vocal cords in most of patients after each injection supporting the evidence of BTX efficacy along that period. Only few minor adverse events from BTX injection were reported in this study, overall there were 3 cases of transient hypophonia and 1 of mild dysphagia. This study confirms the benefit of treatment with BTX in SD by using objective measures that resulted in accordance with subjective assessment of VHI questionnaire. Outcomes of the study also suggest that efficacy of BTX does not decrease with recurring treatments in SD according with previous studies on focal dystonia that proved the efficacy and safety of treatment with neurotoxins for many years [9]. Finally, VL and VS are strongly suggested to be performed to sustain the diagnosis of SD and to assess the response of BTX at the first treatment, later VL and VS can be considered but not required for the following injections and they can be performed on occasion to assess patients and improve treatment over time. Acknowledgments
There are no funding sources for this study.
Conflict of interest The authors do not have financial disclosures or conflict of interest concerning the research related to the manuscript.
References Discussion Voice disorders of neurologic origin require mainly a clinical assessment from neurologists and phoniatricians with good expertise in dystonia and tremor of vocal cords. Instrumental investigations support and confirm diagnosis and can play an important role to identify the correct treatment. VL and VS are very helpful tools to diagnose
1. Jinnah HA, Berardelli A, Comella C, Defazio G, Delong MR, Factor S, Galpern WR, Hallett M, Ludlow CL, Perlmutter JS, Rosen AR, Dystonia Coalition Investigators (2013) The focal dystonias: current views and challenges for future research. Mov Disord 28(7):926–943 2. Daraei P, Villari CR, Rubin AD, Hillel AT, Hapner ER, Klein AM, Johns MM 3rd (2014) The role of laryngoscopy in the diagnosis of spasmodic dysphonia. JAMA Otolaryngol Head Neck Surg 140(3):228–232
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Neurol Sci 3. Rees CJ, Blalock PD, Kemp SE, Halum SL, Koufman JA (2007) Differentiation of adductor-type spasmodic dysphonia from muscle tension dysphonia by spectral analysis. Otolaryngol Head Neck Surg 137(4):576–581 4. Di Nicola V, Fiorella ML, Luperto P, Staffieri A, Fiorella R (2001) Objective evaluation of dysphonia. Possibilities and limitations. Acta Otorhinolaryngol Ital 21(1):10–21 (Review. Italian) 5. Blitzer A (2010) Spasmodic dysphonia and botulinum toxin: experience from the largest treatment series. Eur J Neurol 17(Suppl 1):28–30 6. Albanese A, Sorbo FD, Comella C, Jinnah HA, Mink JW, Post B, Vidailhet M, Volkmann J, Warner TT, Leentjens AF, MartinezMartin P, Stebbins GT, Goetz CG, Schrag A (2013) Dystonia
123
rating scales: critique and recommendations. Mov Disord 28(7):874–883 7. Kima JH, Kimb EY, Jangc S-J, Choia Y (2014) Phonation characteristics of adductor spasmodic dysphonia patients before and after botulinum toxin-A injection. Commun Sci Dis 19(3):402–411 8. Tsuji DH, Hachiya A, Dajer ME, Ishikawa CC, Takahashi MT, Montagnoli AN (2007) Improvement of vocal pathologies diagnosis using high-speed videolaryngoscopy. Otolaryngol Head Neck Surg 137(4):576–581 9. Ramirez-Castaneda J, Jankovic J (2014) Long-term efficacy, safety, and side effect profile of botulinum toxin in dystonia: a 20-year follow-up. Toxicon 90:344–348. doi:10.1016/j.toxicon. 2014.07.009 (Epub 2014 Aug 15)
ORIGINAL ARTICLE
Spasmodic dysphonia follow-up with videolaryngoscopy and voice spectrography during treatment with botulinum toxin Marcello Esposito1 • R. Dubbioso1 • P. Apisa2 • R. Allocca1 • L. Santoro1 U. Cesari2
•
Received: 10 February 2015 / Accepted: 3 May 2015 Ó Springer-Verlag Italia 2015
Abstract Spasmodic dysphonia (SD) is a focal dystonia of laryngeal muscles seriously impairing quality of voice. Adductor SD (ADSD) is the most common presentation of this disorder that can be identified by specialized phoniatricians and neurologists firstly on a clinical evaluation and then confirmed by videolaryngoscopy (VL). Botulinum toxin (BTX) injection with electromyographic guidance in muscles around vocal cords is the most effective treatment. Voice Handicap Index (VHI) questionnaire is the main tool to assess dysphonia and response to treatment. Objective of this study is to perform VL and voice spectrography (VS) to confirm the efficacy of BTX injections over time. 13 patients with ADSD were studied with VHI, VL and VS before and after 4 consecutive treatment with onobotulinumtoxin-A. For each treatment vocal improvement was proved by a significant reduction of VHI score and increase of maximum time phonation and harmonic-tonoise ratio while VL showed the absence of spasm in most of patients. No change of the response to BTX was found between injections. This study supports the efficacy of the treatment of SD with BTX with objective measurements and suggests that the efficacy of recurring treatments is stable over time. Keywords Spasmodic dysphonia Dystonia Botulinum toxin Videolaryngoscopy Voice spectrography
& Marcello Esposito [email protected] 1
Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Via Sergio Pansini, 5, 80131 Naples, Italy
2
Otorhinolaryngology Department, University Federico II of Naples, Naples, Italy
Introduction Spasmodic dysphonia (SD) is a focal dystonia of vocal cords that occasionally is part of a wider neurologic disease or generalized dystonic syndrome, but it usually occurs as isolated disorder in adults [1]. SD presents two main phenotypes on the basis of the abnormal deviation of vocal cords in adduction or in abduction as result of excessive contraction of laryngeal muscles. Adductor SD (ADSD) is the most frequent type and it produces a strangulated quality of voice. ADSD is primarily diagnosed on clinical evaluation that is confirmed by the evidence of excessive spasmodic adduction of false vocal cords on videolaryngoscopy (VL) [2]. Voice spectrography (VS) gives further information on sound alteration, but does not provide specific diagnostic evidences [3]. The most effective treatment of ADSD is botulinum toxin (BTX) injection in thyroarytenoid muscles producing muscle relaxation and reducing excessive adduction of vocal cords. VL can show these changes after BTX injection AND can provide mainly qualitative data of BTX effects in SD while VS can produce quantitative measures including the maximum time phonation (MPT) and harmonic-to-noise ratio (HNR) that are often used in phonetics assessment. MTP is obtained during sustained vowel /a/ after a deep inspiration and normal duration is longer than 18 s. HNR defines the ratio between sound and noise in voice spectrum during spontaneous speech. An outstanding normal voice in silent room at medium intensity should have an HNR score higher than 13 dB [4]. MPT and HNR are reduced in SD and can be increased by BTX action on vocal cords. Clinical benefits from the treatment of SD with BTX occur few days after the injection and last 4–6 months, only minor side effects are reported occasionally [5]. The most used tool to evaluate clinical effectiveness of the treatment
123
Neurol Sci
is the Voice Handicap Index (VHI) that is a questionnaire assessing the functional, emotional, and psychosocial consequences of voice disorders [6]. Reduction of the VHI score after BTX injection in muscles around vocal cords proved the efficacy of this treatment in few studies only on a clinical level but it did not give information on vocal alterations and abnormal contractures of vocal cords. On this background, we aimed to confirm the efficacy of BTX injections for ADSD and especially to evaluate the response of the treatment over time with the use of qualitative and quantitative measure of human voice with VS and VL in addition to clinical features reported by the VHI questionnaire.
Patients and methods 13 consecutive patients with ADSD never treated before with BTX were studied from 2012 to 2014. ADSD was diagnosed on the basis of clinical evaluation performed by a neurologist and a phoniatrician with expertise in dystonia and confirmed with VL showing spasmodic movements in adduction of vocal cords. Each patient received BTX injections in thyroarytenoid muscle in both sides with the aid of EMG guidance. Injections were performed by the phoniatrician supported by a neurophysiologist for the interpretation of EMG recordings. BTX used for the study was onabotulinumtoxin-A with a minimum dose of 2.5 U per vocal cord increasing the dose in case of unsatisfactory response (VHI [ 80). VHI, VS and VL were assessed before the injection and 2 weeks after for 4 consecutive treatments performed every 5 months. VS was recorded during a sustained vowel /a/ followed by pronunciation of an eight-word sentence and MPT and HNR and were obtained from each test. The phoniatrician performed the VL and rated for each patient the reduction or the full absence of spasmodic contraction of false vocal cords.
Results 13 patients (3 M, 10 F) with age ranging from 32 to 73 years (mean age 61 ± 15.8 years) and mean disease duration of 7.6 ± 4.4 years. The dose of onabotulinumtoxin-A given at the first injection was 2.5 U and the mean dose injected in following treatments was 3.26 ± 0.78. The mean score of VHI before each treatment was: 82.0 ± 7.72 (1st injection), 81.8 ± 7.23 (2nd injection), 81.1 ± 3.70 (3rd injection) and 81.2 ± 7.05 (4th injection). After BTX injection the score was: 66.38 ± 3.88 (1st injection), 65.69 ± 3.71 (2nd injection), 65.85 ± 4.63 (3rd injection) and 64.92 ± 4.72 (4th injection). The VHI score reduced significantly after treatment (p \ 0.001, Kruskal–Wallis test). These results were confirmed by Wilcoxon signed rank test, putting forward a significant improvement of VHI score but only after each treatment (p \ 0.001), with no significant effect over time (p [ 0.09) (Fig. 1).The mean duration (s) of MPT before each treatment was: 3.41 s ± 1.18 (1st injection), 3.54 s ± 1.22 (2 injection), 3.62 s ± 1.10 (3rd injection) and 3.62 s ± 1.19 (4th injection). The mean duration of MPT after each treatment was: 10.3 s ± 1.38 (1st injection), 11.5 s ± 1.10 (2nd injection), 12.8 s ± 1.26 (3rd injection) and 13.8 s ± 1.64 (4th injection). The MPT duration improved significantly after treatment (p \ 0.001, Kruskal–Wallis test). These results were confirmed by Wilcoxon signed rank test, putting forward a significant improvement of MPT duration after each treatment (p \ 0.001) and with no significant effect over time (p \ 0.03) (Fig. 2). The mean value of HNR before each treatment was: -3.08 dB ± 1.19 (1st injection), -2.73 dB ± 1.05 (2 injection), -2.80 dB ± 0.76 (3rd injection) and -1.71 dB ± 1.14 (4th injection). The mean value of HNR after each treatment was: 2.07 dB ± 1.02 (1st injection), 2.26 dB ± 1.03 (2nd injection), 2.16 dB ± 0.96 (3rd injection) and 2.03 dB ± 0.94 (4th injection).The HNR ratio improved
Statistical analysis Given the small number of subjects and because the distribution of variables could not be assumed to be approximately normal, all statistical analyses applied were nonparametric tests. The effects of BoNT on the outcome measures (MPT and VHI) were compared by means of the Kruskal–Wallis test. Moreover, we used Wilcoxon signed rank test to evaluate the benefit from BoNT-A injections after each injection and over time. Data were analyzed using software (SPSS v. 19.0 for Windows; SPSS Inc.). The significance level was set as p \ 0.05. Alpha inflation due to multiple comparisons was controlled according Bonferroni’s approach when appropriate. Data are presented as mean ± SD.
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Fig. 1 Effect of BTX injections on VHI score: VHI score reduces significantly after each injection (p \ 0.008)
Neurol Sci
Fig. 2 Effect of BTX injections on MPT. MPT duration increases significantly after each injection (p \ 0.008)
Fig. 3 Effect of BoNT-A injections on HNR. HNR level increases significantly after each injection (p \ 0.02)
significantly after treatment (p \ 0.001, Kruskal–Wallis test). These results were confirmed by Wilcoxon signed rank test, putting forward a significant improvement of HNR only after each treatment (p \ 0.024), with no significant effect over time (p [ 0.96); p values is \0.05 after Bonferroni’s correction for multiple comparisons (Fig. 3). VL showed the presence of false vocal cords spasms in all patients before each treatment (100 %) while the full absence of spasmodic contraction was observed in 53 % of cases (7/13) after the first injection, in 69 % (9/13) after the second injection, in 61 % (8/13) after the third injection and 69 % (9/13) after the fourth injection.
ADSD as VL can disclose abnormal mobility of vocal cords related to different disorders while VS can give more details on the level of vocal impairment [6]. Treatment of ADSD with BTX is proved to be effective mainly on a clinical level on the basis of VHI score and aim of this study was to provide instrumental evidence of persistent benefit from BTX injections over time. After the treatment in all patients spectography showed a prolonged duration of MTP and higher level of HNR [7, 8]. Our study confirmed a significant reduction of VHI score and VS showed significant changes after each injection with quantitative measures. The duration of the MTP and the level of HNR were increased after every treatment and there was no significant difference between each of them. VL cannot provide quantitative measures comparable during the follow-up and the rating from the examiner can be considered mainly as qualitative data correlating with results obtained with VS and VHI questionnaire. With VL the phoniatrician found almost a complete reduction of muscle spasms around vocal cords in most of patients after each injection supporting the evidence of BTX efficacy along that period. Only few minor adverse events from BTX injection were reported in this study, overall there were 3 cases of transient hypophonia and 1 of mild dysphagia. This study confirms the benefit of treatment with BTX in SD by using objective measures that resulted in accordance with subjective assessment of VHI questionnaire. Outcomes of the study also suggest that efficacy of BTX does not decrease with recurring treatments in SD according with previous studies on focal dystonia that proved the efficacy and safety of treatment with neurotoxins for many years [9]. Finally, VL and VS are strongly suggested to be performed to sustain the diagnosis of SD and to assess the response of BTX at the first treatment, later VL and VS can be considered but not required for the following injections and they can be performed on occasion to assess patients and improve treatment over time. Acknowledgments
There are no funding sources for this study.
Conflict of interest The authors do not have financial disclosures or conflict of interest concerning the research related to the manuscript.
References Discussion Voice disorders of neurologic origin require mainly a clinical assessment from neurologists and phoniatricians with good expertise in dystonia and tremor of vocal cords. Instrumental investigations support and confirm diagnosis and can play an important role to identify the correct treatment. VL and VS are very helpful tools to diagnose
1. Jinnah HA, Berardelli A, Comella C, Defazio G, Delong MR, Factor S, Galpern WR, Hallett M, Ludlow CL, Perlmutter JS, Rosen AR, Dystonia Coalition Investigators (2013) The focal dystonias: current views and challenges for future research. Mov Disord 28(7):926–943 2. Daraei P, Villari CR, Rubin AD, Hillel AT, Hapner ER, Klein AM, Johns MM 3rd (2014) The role of laryngoscopy in the diagnosis of spasmodic dysphonia. JAMA Otolaryngol Head Neck Surg 140(3):228–232
123
Neurol Sci 3. Rees CJ, Blalock PD, Kemp SE, Halum SL, Koufman JA (2007) Differentiation of adductor-type spasmodic dysphonia from muscle tension dysphonia by spectral analysis. Otolaryngol Head Neck Surg 137(4):576–581 4. Di Nicola V, Fiorella ML, Luperto P, Staffieri A, Fiorella R (2001) Objective evaluation of dysphonia. Possibilities and limitations. Acta Otorhinolaryngol Ital 21(1):10–21 (Review. Italian) 5. Blitzer A (2010) Spasmodic dysphonia and botulinum toxin: experience from the largest treatment series. Eur J Neurol 17(Suppl 1):28–30 6. Albanese A, Sorbo FD, Comella C, Jinnah HA, Mink JW, Post B, Vidailhet M, Volkmann J, Warner TT, Leentjens AF, MartinezMartin P, Stebbins GT, Goetz CG, Schrag A (2013) Dystonia
123
rating scales: critique and recommendations. Mov Disord 28(7):874–883 7. Kima JH, Kimb EY, Jangc S-J, Choia Y (2014) Phonation characteristics of adductor spasmodic dysphonia patients before and after botulinum toxin-A injection. Commun Sci Dis 19(3):402–411 8. Tsuji DH, Hachiya A, Dajer ME, Ishikawa CC, Takahashi MT, Montagnoli AN (2007) Improvement of vocal pathologies diagnosis using high-speed videolaryngoscopy. Otolaryngol Head Neck Surg 137(4):576–581 9. Ramirez-Castaneda J, Jankovic J (2014) Long-term efficacy, safety, and side effect profile of botulinum toxin in dystonia: a 20-year follow-up. Toxicon 90:344–348. doi:10.1016/j.toxicon. 2014.07.009 (Epub 2014 Aug 15)
