Botulinum Toxin Therapy: A Series of Clinical Studies on Patients with Spasmodic Dysphonia in Japan.

Spasmodic dysphonia (SD) is a rare voice disorder caused by involuntary and intermittent spasms of the laryngeal muscles. Both diagnosis and treatment have been controversial. Therefore, a series of clinical studies has recently been conducted in Japan. A nationwide epidemiological survey revealed that adductor SD predominated (90-95% of all cases; 3.5-7.0/100,000), principally among young women in their 20s and 30s. To facilitate early diagnosis, we created diagnostic criteria for SD and a severity grading system. The diagnostic criteria include the principal and accompanying symptoms, clinical findings during phonation, the treatment response, and the differential diagnoses. The severity grade is determined using a combination of subjective and objective assessments. Botulinum toxin (BT) injection is the treatment of choice; however, there have been few high-quality clinical studies and BT has been used off-label. We conducted a placebo-controlled, randomized, double-blinded clinical trial of BT therapy; this was effective and safe. BT treatment is now funded by the Japanese medical insurance scheme. Studies thus far have facilitated early diagnosis and appropriate therapy; they have fostered patient awareness of SD.

The prevalence and clinical features of spasmodic dysphonia: A review of epidemiological surveys conducted in Japan.

OBJECTIVES: Spasmodic dysphonia (SD) is a rare disease and its epidemiological status is unclear. This review aimed to explore the current prevalence and clinical features of SD in Japan. METHODS: We reviewed Japanese surveys of SD and compared them to surveys reported from other countries. We focused on SD prevalence, clinical features (SD type, sex and age), and treatment modalities. RESULTS: The SD prevalence in Japan was 3.5-7.0/100,000, similar to that in Rochester (NY, USA) and Iceland. Adductor SD predominated (90-95%) and females were four-fold more likely to be affected than males. Mean age at onset was approximately 30 years in Japan. Several years elapsed from onset to diagnosis. The most frequent treatment was botulinum toxin injection, and surgical intervention, particularly type 2 thyroplasty is becoming more popular. CONCLUSIONS: Our review demonstrated some differences of clinical features of SD in Japan compared with other countries, such as a greater female predominance and younger age of onset. Many physicians and patients may be unfamiliar with the clinical features of SD leading to delayed of diagnosis. Therefore, we proposed diagnostic criteria to facilitate early diagnosis and an appropriate choice of treatment modalities.

A summary of the Clinical Practice Guideline for the Diagnosis and Management of Voice Disorders, 2018 in Japan.

OBJECTIVE: To develop a summary of the first version of the Clinical Practice Guideline of Voice Disorders for Diagnosis, Management, and Treatment in Japan by the Clinical Practice Guideline Committee of the Japan Society of Logopedics and Phoniatrics and The Japan Laryngological Association. The 2018 recommendations, based on a review of the scientific literature, are intended to serve as clinical practice guidelines for the diagnosis, management, and treatment of voice disorders in Japan. METHODS: A summary of the original version of the Clinical Practice Guideline of Voice Disorders for Diagnosis, Management, and Treatment in Japan was described. Recommendations for the diagnosis, management, and treatment of voice disorders were prepared. Twelve clinical questions (CQs) regarding the diagnosis, management, treatment, and effectiveness of therapy for voice disorders were also prepared. RESULTS: A summary of the first version of the clinical practice guidelines for the diagnosis, management, and therapy of voice disorders was prepared and is presented. Additionally, answers to the 12 CQs on the diagnosis, management, treatment, and effectiveness of voice disorder therapy were prepared, and include evidence-based recommendations. CONCLUSION: These guidelines present a summary of the standard approaches for the diagnosis and treatment of voice disorders and relevant CQs that consider the medical environments in Japan. We hope that the guidelines will assist physicians in clinical settings for patients with voice disorders.

Reliability and Validity of Speech Evaluation in Adductor Spasmodic Dysphonia.

OBJECTIVES: The aim of this study was to evaluate speech in patients with adductor spasmodic dysphonia (ADSD) by perceptual evaluations and acoustic measures, and to examine the reliability and validity of these measures. METHODS: Twenty-four patients with ADSD and 24 healthy volunteers were included in the study. Speech materials consisted of three sentences constructed from serial voiced syllables to elicit abductor voice breaks. Three otolaryngologists rated the degree of voice symptoms using a visual analog scale (VAS). VAS sheets with five 100-mm horizontal lines were given to each rater. The ends of the lines were labeled normal vs severe, and the five lines were labeled as overall severity of each of the four speech symptoms (strangulation, interruption, tremor and strained speech). Nine words were selected for acoustic analysis, and abnormal acoustic events were classified into one of the three categories. To evaluate the intra- and inter-rater and intermeasurer reliabilities of the VAS scores or acoustic measures, Pearson r correlations were calculated. To examine the validity of perceptual evaluations and acoustic measures, the sensitivity and the specificity were calculated. RESULTS: Pearson r correlation coefficients for overall severity showed the highest intra- and inter-rater reliabilities. For acoustic events, the intrameasurer reliabilities were r = .645 (frequency shifts), r = .969 (aperiodic segments), and r = 1.0 (phonation breaks), and the intermeasurer reliability ranged from r = .102 to r = 1.0. Perceptual evaluation showed high sensitivity (91.7%) and specificity (100%), whereas acoustic analysis showed low sensitivity (70.8%) and high specificity (100%). CONCLUSION: Both perceptual evaluation and acoustic measures alone were found likely to overlook patients with true ADSD.

Perioperative complications and safety of type II thyroplasty (TPII) for adductor spasmodic dysphonia.

Type II thyroplasty (TPII) is one of the surgical options offered in the management of adductor spasmodic dysphonia (AdSD); however, there have been no detailed reports of its safety and associated complications during the perioperative period. Our aim was to assess the complications and safety of TPII. TPII was performed for consecutive 15 patients with AdSD from April 2012 through May 2014. We examined retrospectively the perioperative complications, the degree of surgical invasion, and recovery process from surgery. All patients underwent successful surgery under only local anesthesia. Vocal fold erythema was observed in 14 patients and vocal fold edema in 10 patients; however, all of them showed complete resolution within 1 month. No patient experienced severe complications such as acute airway distress or hemorrhage. Fourteen patients were able to have oral from the 1st postoperative morning, with the remaining patient able to have oral intake from the 2nd postoperative day. In addition, no patient experienced aspiration postoperatively. In conclusion, only minor complications were observed in association with TPII in this study. No dysphagia was observed postoperatively, which is an advantage over other treatments. The results of our study suggest that TPII is a safe surgical treatment for AdSD.

Voice Onset Time for the Word-Initial Voiceless Consonant /t/ in Japanese Spasmodic Dysphonia-A Comparison With Normal Controls.

OBJECTIVES: Voice onset time (VOT) for word-initial voiceless consonants in adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD) patients were measured to determine (1) which acoustic measures differed from the controls and (2) whether acoustic measures were related to the pause or silence between the test word and the preceding word. METHODS: Forty-eight patients with ADSD and nine patients with ABSD, as well as 20 matched normal controls read a story in which the word "taiyo" (the sun) was repeated three times, each differentiated by the position of the word in the sentence. The target of measurement was the VOT for the word-initial voiceless consonant /t/. RESULTS: When the target syllable appeared in a sentence following a comma, or at the beginning of a sentence following a period, the ABSD patients' VOTs were significantly longer than those of the ADSD patients and controls. Abnormal prolongation of the VOTs was related to the pause or silence between the test word and the preceding word. CONCLUSIONS: VOTs in spasmodic dysphonia (SD) may vary according to the SD subtype or speaking conditions. VOT measurement was suggested to be a useful method for quantifying voice symptoms in SD.

Important points for primary cleft palate repair for speech derived from speech outcome after three different types of palatoplasty.

OBJECTIVE: This study was performed to investigate speech outcomes after three different types of palatoplasty for the same cleft type. The objective of this study was to investigate the surgical techniques that are essential for normal speech on the basis of each surgical characteristic. METHODS: Thirty-eight consecutive nonsyndromic patients with unilateral complete cleft of the lip, alveolus, and palate were enrolled in this study. Speech outcomes, i.e., nasal emission, velopharyngeal insufficiency, and malarticulation after one-stage pushback (PB), one-stage modified Furlow (MF), or conventional two-stage MF palatoplasty, were evaluated at 4 (before intensive speech therapy) and 8 (after closure of oronasal fistula/unclosed hard palate) years of age. RESULTS: Velopharyngeal insufficiency at 4 (and 8) years of age was present in 5.9% (0.0%), 0.0% (0.0%), and 10.0% (10.0%) of patients who underwent one-stage PB, one-stage MF, or two-stage MF palatoplasty, respectively. No significant differences in velopharyngeal function were found among these three groups at 4 and 8 years of age. Malarticulation at 4 years of age was found in 35.3%, 10.0%, and 63.6% of patients who underwent one-stage PB, one-stage MF, and two-stage MF palatoplasty, respectively. Malarticulation at 4 years of age was significantly related to the presence of a fistula/unclosed hard palate (P<0.01). One-stage MF palatoplasty that was not associated with postoperative oronasal fistula (ONF) showed significantly better results than two-stage MF (P<0.01). Although the incidences of malarticulation at 8 years of age were decreased in each group compared to at 4 years of age, the incidence was still high in patients treated with two-stage MF (45.5%). On the whole, there was a significant correlation between ONF/unclosed hard palate at 4 years of age and malarticulation at 8 years of age (P<0.05). CONCLUSION: Appropriate muscle sling formation can compensate for a lack of retropositioning of the palate for adequate velopharyngeal closure. Early closure of the whole palate and the absence of a palatal fistula were confirmed to be essential for normal speech. To avoid fistula formation, multilayer repair of the whole palate may be critical.

Voice-related quality of life after treatment of laryngeal cancer.

OBJECTIVE: To determine patient-perceived voice-related quality of life in patients treated with various methods based on the results of Voice-Related Quality of Life (VRQOL) and Voice Handicap Index-10 (VHI-10) questionnaires. DESIGN: The VRQOL and VHI-10 questionnaires. SETTING: University hospital. PATIENTS: One hundred thirty-seven patients who had received definitive treatment of laryngeal cancer were followed-up at Hokkaido University Hospital, Sapporo, Japan, and were alive with no evidence of malignancy at the time of the survey. MAIN OUTCOME MEASURE: Patient-perceived voice-related quality of life based on the results of the VRQOL and VHI-10 questionnaires. RESULTS: The mean VRQOL scores for patients who had undergone radiotherapy (n = 63), chemoradiotherapy (n = 29), laser surgery (n = 14), or total laryngectomy (n = 27) as final treatment of laryngeal cancer were 92.6, 92.9, 85.5, and 68.4, respectively; the mean VHI-10 scores were 2.87, 2.34, 5.43, and 11.26, respectively. CONCLUSION: The VRQOL and VHI-10 questionnaires are important in judging the overall effectiveness of treatment options for laryngeal cancer.

The diagnosis and management of globus: a perspective from Japan.

PURPOSE OF REVIEW: The etiology of globus is multifactorial and its management is controversial. Recent findings in the etiology and diagnosis of globus are discussed, and a subjective opinion on its management is presented. RECENT FINDINGS: Although there is considerable debate concerning the role of gastroesophageal reflux disease (GERD) in patients with globus, the globus symptom score has been shown to be significantly higher in patients with GERD than in those without GERD. This definite association between GERD and globus leads to the practical division of patients with globus into two groups: the GERD/laryngopharyngeal reflux (LPR)-induced and non-GERD/LPR groups. When the presence of GERD or LPR or both is established in patients with globus, management of this condition should be considered. Owing to limitations in the technology for the detection of GERD/LPR, precise discrimination between the two groups is still difficult. For practical purposes, empirical approaches for targeting GERD in patients with globus appear to be justified. A 24 h pH-metry/multichannel intraluminal impedance test may increase the detection of reflux events in patients with globus. SUMMARY: A practical approach for dividing patients with globus into GERD/LPR-induced and non-GERD/LPR groups is introduced.

Development of phonemic distinction in Japanese preschool children.

The literature suggests that, within several months of birth, infants develop the ability to distinguish between different speech sounds. However, the time frame for discrimination of a specific phonological system remains unclear. In order to clarify this, the discrimination responses of 211 preschool children were examined. The test battery consisted of 16 pairs of Japanese words, of which each pair contained distinctive phonemes in the initial syllables only. Test stimuli were presented in 2 ways: one as a whole test word and the other as only the initial syllable, which contained the target phoneme. When the test stimuli were whole words, correct discrimination exceeded 60% for test pairs in age groups older than 2:06-2:11 chronological age (years:months). However, when initial syllables were used, correct discrimination only exceeded 60% in age groups older than 3:06-3:11. Phonemic distinction within syllables seems to be established during early preschool age in Japanese children.

Evaluation of upper abdominal symptoms using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease in patients with laryngopharyngeal reflux symptoms.

BACKGROUND: The purpose of the study was to evaluate upper abdominal symptoms in laryngopharyngeal reflux (LPR) patients and changes in both upper abdominal and LPR symptoms before and after acid-suppression therapy. METHODS: In 100 patients with LPR symptoms, upper abdominal and LPR symptoms were evaluated by using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) and the LPR symptom scoring system, respectively. In the 52 assessable patients, changes in these symptoms before and after acid-suppression therapy were evaluated. RESULTS: Upper abdominal symptoms were reported by 96/100 LPR patients: 89 responded positively to at least one of the questions about acid reflux-related symptoms and 89 to at least one of those about dysmotility-like symptoms. There was poor correlation between positive rates to FSSG upper abdominal symptom questions and the frequency of reported laryngopharyngeal symptoms. There were significant reductions in the frequency of acid reflux-related symptoms, dysmotility-like symptoms, and laryngopharyngeal symptoms after acidsuppression therapy. The LPR symptom score decreased to less than half the pretreatment score in 25 subjects (therapeutic response group). The pretreatment frequency of dysmotility-like symptoms seemed to be higher in the nonresponse group than in the response group, although the difference was not significant. There was no significant difference between the two groups in the pretreatment frequency of acid reflux-related symptoms. CONCLUSIONS: The majority of these Japanese LPR patients experienced some form of upper abdominal symptoms. The frequency of dysmotility-like symptoms was similar to that of acid reflux-related symptoms. The pretreatment frequency of dysmotility-like symptoms, but not of acid reflux-related symptoms, might be a predictor of patient response to acid-suppression therapy.

Acid-suppression therapy offers varied laryngopharyngeal and esophageal symptom relief in laryngopharyngeal reflux patients.

It is widely accepted that laryngopharyngeal reflux requires more aggressive and prolonged therapy than gastro-esophageal reflux disease. Otolaryngologists often observe that laryngopharyngeal symptoms, such as throat clearing, hoarseness, cough, and globus pharyngeus, are slower to resolve than esophageal symptoms, such as heartburn and regurgitation. The aim of this was to provide empirical evidence to support this observation and to carry out a detailed investigation of the differences between these symptoms. Forty-five patients with laryngopharyngeal and esophageal symptoms received acid-suppression therapy that involved the continuous administration of a proton-pump inhibitor for up to 6 months. We investigated the differences in response to acid-suppression therapy between patients suffering from laryngopharyngeal and esophageal symptoms, respectively, who received upper gastrointestinal endoscopy and were assayed for serum Helicobacter pylori antibodies. The significance of the rate of symptom improvement was estimated by Kaplan-Meier analysis and the logrank test. Laryngopharyngeal symptoms improved significantly more slowly than esophageal symptoms following acid-suppression therapy (49.8 vs. 78.3%, 60 days after the start of acid suppression; P = 0.003). These differences were observed both in patients with erosive esophagitis (P = 0.008) and in H. pylori-seronegative patients (P = 0.001).

[Three cases of muscle tension dysphonia improved using proton pump inhibitors].

We report 3 cases of muscle tension dysphonia (MTD), all involving women 44 to 68 years old, recovered using proton pump inhibitors (PPI). Case 1 had open posterior commissure (MTD Type I) and Cases 2 and 3 supraglottis compression (MTD Type II, III). It is generally assumed that functional dysphonia with maladjustment of laryngeal muscle tension is caused by improper phonation and/or emotional disorder. Our cases, however, suggest that laryngopharyngeal reflux (LPR) may also relate to the occurrence of MTD.

Velopharyngeal insufficiency in hemifacial microsomia: analysis of correlated factors.

OBJECTIVE: To investigate the incidence of unilateral hypodynamic palate (UHP) and velopharyngeal insufficiency (VPI) in hemifacial microsomia (HFM), and to determine the dysmorphic manifestations having significant associations with UHP/VPI in HFM. STUDY DESIGN: This was a nonrandomized study of 48 patients with unilateral HFM without cleft palate. The correlation between each anomaly and UHP/VPI was analyzed statistically. In addition, we observed 4 HFM patients with cleft palate to examine the influence on cleft palate speech. RESULTS: The incidence of UHP in HFM was 50.0% and that of VPI was 14.6%. All the VPI patients had UHP. Severe micrognathia and soft tissue deficiency, macrostomia, and mental retardation were significant risk factors for developing VPI in HFM. Moreover, UHP exacerbated speech in HFM with cleft lip and palate. CONCLUSIONS: Significant correlations were detected between VPI and HFM. This finding should be helpful in the overall management of HFM.

Helicobacter pylori seropositivity predicts outcomes of acid suppression therapy for laryngopharyngeal reflux symptoms.

OBJECTIVES: Although an inverse relationship has been reported between the rates of reflux esophagitis and Helicobacter pylori infection in Japan, infection rates among patients complaining of laryngopharyngeal reflux symptoms, such as abnormal laryngopharyngeal sensation, chronic coughing, and hoarseness, have not previously been investigated. The effects of H. pylori infection on outcomes of acid suppression therapy have not been studied. STUDY DESIGN: Retrospective cohort study. METHODS: We investigated the relationships between H. pylori antibody positivity, laryngopharyngeal reflux symptoms, objective laryngopharyngeal findings, and rate of response to acid-suppression therapy in 42 subjects who were diagnosed with gastroesophageal reflux disease, using upper gastrointestinal endoscopy, and were assayed for the serum H. pylori antibody. RESULTS: The incidence of H. pylori antibody positivity in the targeted patient group was 59.5%. Kaplan-Meier analysis showed that the laryngopharyngeal symptom-improvement rate, measured using the symptom score, was significantly lower for H. pylori antibody-negative cases than for H. pylori antibody-positive cases (30.0 vs. 84.6%; P = .002) 60 days after the start of acid-suppression therapy. No significant differences in the esophageal symptom-improvement rate were noted between the two groups (76.2 vs. 89.5%; P = .576) CONCLUSIONS: By focusing on the involvement of H. pylori infection in laryngopharyngeal reflux, we determined the relationships between H. pylori antibody positivity and response to acid-suppression therapy among patients. The laryngopharyngeal, not esophageal, symptom relief by acid-suppression therapy was significantly lower among H. pylori antibody-negative cases than among antibody-positive cases.

Voice restoration by primary insertion of indwelling voice prosthesis following circumferential pharyngolaryngectomy with free jejunal graft.

BACKGROUND: Voice restoration after circumferential pharyngolaryngectomy (CPL) with free jejunal graft remains a difficult problem to solve. Few reports have analyzed the success rate and complications following primary insertion of indwelling voice prostheses during CPL with free jejunal graft. PATIENTS AND METHODS: Eight patients who underwent CPL with free jejunal graft had a Groningen voice prosthesis inserted as a tracheoesophageal (TE) shunt at the time of oncological surgery. A 10-point scale was used to assess each patient's speech intelligibility. Complications following the voice prosthesis insertion were also analyzed. RESULTS: Six of the eight patients (75%) achieved excellent speech intelligibility and the remaining two patients (25%) were judged as moderate. Six of the eight patients (75%) used the TE shunt as their major means of daily communication. Leakage through or around the prosthesis, which occurred in six (75%) patients, was the most frequent prosthesis-related complication. CONCLUSIONS: This safe and reliable technique can be effective in improving the quality of life in selected patients undergoing CPL.

The prevalence of laryngeal pseudosulcus among Japanese patients with laryngopharyngeal reflux related symptoms.

Infraglottic edema extending from the anterior commissure to the posterior larynx, called the laryngeal pseudosulcus, may have some value in the diagnosing of laryngopharyngeal reflux (LPR). The purpose of this study is to evaluate the prevalence, sensitivity and specificity of this finding among Japanese patients with LPR-related symptoms. Forty-three patients diagnosed as LPR based on their symptoms and 42 control patients without LPR were enrolled. The presence of pseudosulcus was determined with transnasal fiberoptic laryngoscopy. Thirty-seven of the 43 patients with LPR and 13 of the 42 control patients had evidence of laryngeal pseudosulcus (p<0.001). The sensitivity and specificity of pseudosulcus in the symptom-based diagnosis of LPR are 86 and 69%, respectively. This study shows that laryngeal pseudosulcus is highly correlated with LPR-related symptoms. The presence of this finding is suggestive of LPR.