Thalamic Deep Brain Stimulation for Spasmodic Dysphonia: A Phase I Prospective Randomized Double-Blind Crossover Trial

Abstract

Background: Adductor spasmodic dysphonia (SD) is a dystonia of the vocal folds causing difficulty with speech. The current standard of care is repeated botulinum toxin injections to weaken the adductor muscles. We sought to ameliorate the underlying neurological cause of SD with a novel therapy-deep brain stimulation (DBS).

Objective: To assess the safety of DBS in SD through phase I trial, and to quantify the magnitude of any benefit.

Methods: Six patients had left ventral intermediate nucleus (Vim) thalamic DBS and were randomized to 3 mo blinded-DBS "on" or "off" followed by a crossover. Primary outcomes were quality of life and quality of voice during the blinded phase. Patients continued with open-DBS "on." Secondary outcomes were comparisons of pre- and 1-yr cognitive, mood, and quality of life. This trial was registered with ClinicalTrials.gov (NCT02558634).

Results: There were no complications. Every patient reported an improvement in quality of life (P = .07) and had an improvement in quality of their voice (P = .06) when their blinded DBS was "on" versus "off." The trend did not reach statistical significance with the small sample size. Secondary outcomes showed no difference in cognition, an improvement in mood, and quality of life at 1 yr.

Conclusion: This phase I randomized controlled trial confirmed that DBS can be performed safely in patients with SD. Blinded DBS produced a strong trend toward improved quality of life and objective quality of voice despite the small sample size. The cerebellar circuit, not the pallidal circuit, appears to be crucial for motor control of the vocal folds.

Keywords: Deep brain stimulation; Quality of life; Randomized control trial; Spasmodic dysphonia.

© Congress of Neurological Surgeons 2021.

Figures

FIGURE 1.

Trial profile. Flow diagram for the randomized clinical crossover trial. Primary analyses were during the blinded phase (orange) and secondary analyses during the open phase (yellow).

FIGURE 2.

Quality of life. Box plot of the median and interquartile range of the V-RQOL for the cohort during each of the 4 experimental settings. Higher scores are better with scores below 50 considered “poor,” 51 to 60 “fair,” 61 to 75 “good,” 76 to 85 “very good,” above 85 “excellent.” In the blinded phase of the study, the median effect size was 55.7 with the 95% CI 33.5 to 63.5. This effect size was enough to improve the cohort's median score of 2 categories from “poor” to “good.” The randomized comparison of DBS ON-OFF and OFF-ON was not significant.

FIGURE 3.

Changes in individual quality of life scores during blinded-DBS “off” and “on.” The V-RQOL for each subject following 3 mo of blinded-DBS “off” and “on.” Higher scores are better with score below 50 considered “poor,” 51 to 60 “fair,” 61 to 74 “good,” 75 to 85 “very good,” and above 85 “excellent.” Arrows show the sequence of randomization.

FIGURE 4.

Quality of voice. Box plot of the median and interquartile range of the overall severity component of the USDRS for the cohort during each of the 4 experimental settings. Lower scores are better. In the blinded phase of the study, the median effect size was 1.25. The randomized comparison of DBS ON-OFF and OFF-ON was not significant.

FIGURE 5.

Changes in individual quality of voice scores during blinded-DBS “off” and “on.” The overall USDRS for each subject following 3 mo of blinded-DBS “off” and “on.” Lower scores are better. Arrows show the sequence of randomization.

FIGURE 6.

Patient perceived voice handicap measured by the VHI. Box plot of the median and interquartile range of the VHI for the cohort during each of the 4 experimental settings. Lower scores are better with below 30 considered “minimal,” 31 to 60 “moderate,” and above 60 “severe.” Patients had better scores (P = .028) during the blinded-DBS “on” than the blinded-DBS “off.” Patients also had better scores (P = .027) at the 1-yr open-DBS “on” timepoint compared to their preoperative evaluation.