The main objective of this study was to assess and compare the results of BTX injection treatment between patients with LD and VT. We have found that BTX treatments have improved significantly the VHI-10, grade of dysphonia on the VAS and G, S and I from the GRBAS-I scale in both patients with LD and VT. Furthermore, there was no significant alteration in the MPT except for patients with VT after the first injection. When we have compared treatment responses between patients with LD and VT, we have found that patients with LD seem to have a better response following treatment with BTX.
Many treatments have been proposed for LD. Truthfully, many authors have tried to treat it with oral medications, such as baclofen or benzodiazepines, with limited success [11]. Aside from some rare cases of dystonia responsive to levodopa, there are no drugs with proven efficacy to treat LD [19]. Since Blitzer described the use of BTX injection in 1986 [20], it has been considered by most authors the mainstay of treatment [9]. In fact, many previous studies have shown an improvement in the VHI, subjective self-assessed grade of dysphonia, mean fundamental frequency, perturbation and spectrographic analysis, jitter, voice break factor and mean airflow with no variation in the maximum phonation time, following BTX injection [21,22,23]. In accordance with these results, patients with LD in this study have shown an improvement in the VHI-10, grade of dysphonia in the VAS, G, S and I in the GRBAS-I scale after treatment with BTX injection with a further improvement in all these variables with further injections. As treatment with BTX injection is temporary, and repetitive injections are required in order to control LD symptoms, some authors use more permanent treatments such as type II thyroplasty [24], laser mioneurectomy [25] and denervation-reinnervation procedures [26]. Even though these procedures seem to be effective in the long-term, they are more invasive and irreversible. We have been doing BTX injections in our institution for over a decade, with good results, and our patients usually prefer a less invasive and reversible treatment, even with the need of repetitive procedures. Furthermore, as Sataloff stated, a cure for LD may occur in our lifetime and while BTX treatment would not interfere with a patient’s ability to receive curative therapy, surgery may lead to irreversible changes that can interfere with it [27].
In our practice, BTX injections are performed with electromyographic control. We believe that with electromyographic controlled injections are more accurate than with transoral or transnasal injections and that injection accuracy is important for treatment success. On the other hand, in a randomized trial there were no differences in outcomes between EMG and fiberoptic guidance injections in the treatment of adductor spasmodic dysphonia in experienced hands [28]. Thus, in experienced hands, fiberoptic guided BTX injections may be a viable alternative in centers without access to laryngeal EMG, but in cases of treatment failure or inexperience with this technique, we believe that patients with LD should be referred to centers with access to laryngeal EMG for BTX treatment.
VT is treated in most cases in accordance to the underlying associated pathology such as propranolol or primidone for essential tremor and levodopa for Parkinson’s disease [12]. However, since these medications don’t seem to be as effective to treat laryngeal tremor, many authors advocate the use of BTX injections to treat VT [14]. In fact, many studies have shown that treatment with BTX injection improves the VHI-10, acoustic and perceptual measurements in patients with VT [29,30,31]. In accordance, we have found that BTX injection has led to an improvement int the VHI-10 score, grade of dysphonia on the VAS and G, S, and I scores from the GRBAS-I scale, with a further improvement of the VAS, G and I with the continuation of the treatment. In all patients from our cohort, BTX injection was performed bilaterally in the TA muscle. Some recent studies point for an improvement in symptomatic control in patients with mixed or vertical VT when a concomitant strap muscle injection is performed [32]. Thus, with a careful selection, the concomitant injection in the strap muscle of patients with VT may further improve our results in the VT group, but since we have only started to do so recently and haven’t included patients with strap muscle injection in this study, we don’t have yet sufficient data to support this hypothesis.
Some patients with VT associated with Parkinson’s disease or essential tremor, may also present with hypophonia and glottic insufficiency, which has been treated by some authors with injection augmentation [33, 34]. A cross-over study compared the success of essential vocal tremor treatment with BTX and injection augmentation and found that there is no clear advantage of injection augmentation in comparison to BTX and suggest that a trial for augmentation should be reserved for patients whose symptomatic control with BTX is poor enough to discontinue the treatment [35]. We believe that the concomitant presence of hypophonia and glottic insufficiency in patients with Parkinson’s disease and essential tremor may justify a significant decrease in the MPT after the first BTX injection in patients with VT. In fact, BTX injections result in a temporary paresis of the TA muscle that could further increase the glottic insufficiency.
Previous studies seem to show a superior improvement after BTX injections in patients with dystonic tremor in comparison to VT [31, 36]. In this study we have included patients with dystonic tremor in the VT group since treatment results were more similar to VT in comparison to LD and in order to increase the sample of the VT group. While we understand that this may have led to a bias, both dystonic tremor and isolated VT patients have shown a significant improvement in the VHI-10, grade of dysphonia in VAS and G and I in the GRBAS-I scale (results not reported). Furthermore, there were no significant differences in outcome variations following treatment of dystonic tremor and isolated VT, even though these results might be biased due to a small sample size when we separate these two groups (results not reported). It would be of particular interest to do future studies with higher samples (for example, multicentric studies) that could compare the results with BTX treatment between LD, dystonic tremor and isolated VT.
To our knowledge, there are no previous studies comparing treatment responses between LD and VT following BTX injection. We have found patients with LD had a significant higher improvement in the grade of dysphonia on the VAS and S and a non-significant but higher improvement in the VHI-10 scale, G and I after the first injection. Furthermore, with the continuation of treatment, patients with LD have shown a significant higher improvement in the G, S and I and a non-significant higher improvement in the VHI-10 scale and VAS.
It was previously found that patients with LD seem to need relatively higher doses of BTX (6.8 U) in comparison to VT (5.02 U) [37]. On the other hand, we didn’t find any significant difference in the BTX dose that yielded the best response neither in the treatment interval between LD (4.17 U; 5.9 months) or VT (4.95 U; 6.7 months). This difference may be explained by a smaller sample size in our study or differences in exclusion criteria, since Orbelo et al. have excluded patients with more generalized neurological disorders [37].
This study has some limitations. Firstly, it is an observational retrospective study with possible bias due to lack of information on clinical data. Furthermore, laryngeal movement disorders are rare and a smaller sampler size may limit statistical differences. Thus, to increase sample size, we have included patients with dystonic tremor in the VT group as we have discussed previously. Moreover, we haven’t excluded patients with more generalized neurological disorders, since, in our experience, they seem to have similar benefit with BTX treatment and they represent an important percentage of our practice. Lastly, the differential diagnosis between LD, VT and dystonic tremor is difficult and requires a high level of experience. In order to reduce misdiagnosis to a minimum, we have used a detailed diagnosis protocol that was previously described by our group [3].
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