Abstract
Objective:
To determine the effects of globus pallidus interna (GPi) deep brain stimulation (DBS) on speech and voice quality of patients with primary, medically refractory dystonia.
Methods:
Voices of 14 patients aged ≥18 years (males=7 and females=7) with primary dystonia (DYT1 gene mutation dystonia=4, cervical dystonia=6, and generalized dystonia=4) with bilateral GPi DBS were assessed. Five blinded raters (two fellowship-trained laryngologists and three speech/language pathologists) evaluated audio recordings of each patient pre- and post-DBS. Perceptual voice quality was rated using the Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale and changes in speech intelligibility were assessed with the Clinical Global Impression of Severity (CGI-s) instrument. Inter-rater and intra-rater reliability rates for perceptual voice ratings were assessed using the kappa coefficient.
Results:
Voice quality parameters showed mean improvements in Grade (p<0.0001), Roughness (p=0.0043), and Strain (p<0.0001) 12 months post-DBS. Asthenia increased from baseline to 6 months (p=0.0022) and declined significantly from 6 to 12 months (p=0.0170). Breathiness did not change significantly over time. Speech intelligibility also improved from 6–12 months (p=0.0202) and from pre-DBS to 12 months post-DBS (p=0.0022). Grade and Strain ratings had nearly perfect and substantial inter-rater agreement (0.84 and 0.71, respectively).
Conclusions:
Voice and speech intelligibility improved after bilateral GPi DBS for dystonia. GPi DBS may emerge as a potential treatment option for patients with medically refractory laryngeal dystonia.
Keywords: Primary dystonia, Voice, Deep Brain Stimulation, Speech, Globus Pallidus Interna
1.1. INTRODUCTION
Movement disorders such as essential tremor (ET), Parkinson’s disease (PD), and primary dystonia are frequently accompanied by dysarthria and dysphonia. Proposed mechanisms for these complications include interference with speech and voice – either directly affecting muscles involved in these processes, or indirectly by causing dysfunction due to the overlap between movement regulation and speech and voice modulation [1,2]. Deep brain stimulation (DBS) is approved by the U.S. Food and Drug Administration (FDA) for treatment of medically refractory motor symptoms of ET and PD. DBS of globus pallidus interna (GPi) has a Humanitarian Device Exemption (HDE) from the FDA and has emerged as the surgical treatment of choice for adults and children with medically refractory, disabling motor symptoms of primary (idiopathic) dystonia. While DBS of subthalamic nucleus (STN), ventral intermedius (VIM) nucleus, and GPi improve motor symptoms of PD, ET, and primary dystonia, it may also have a negative effect on voice and speech. The majority of studies examine the effects of DBS on speech quality in patients with PD, with many studies showing that DBS can have deleterious effects on speech leading to dysarthria [3–5]. However, the effects of DBS on speech and voice in patients with primary dystonia are still unclear. The gold standard of treatment for focal dystonias like spasmodic dysphonia [6], laryngeal dystonia [7], oromandibular dystonia [8], writer’s cramp [9] and blepharospam [10] has been botulinum toxin injection. Only recently have unilateral and bilateral DBS been explored as a treatment option for focal dystonias [11,12].
Past research on DBS as a treatment for patients with dystonia has been found in neurology literature [15]. Unfortunately, these studies do not use specific voice and speech outcome measures to adequately characterize perturbations with respect to voice and speech. Most studies have focused on the effect of bilateral DBS for dystonia on speech intelligibility and whether dysarthria improved or worsened after DBS, or the effect of stimulation parameters on speech and voice [4,16]. Follow-up has largely been limited to reported 6 months after surgery, with only a few studies extending later [13,17]. Risch at al conducted a study with 15 patients diagnosed with cervical dystonia who received bilateral GPi DBS; they examined its effects on parameters of voice and speech such as articulation rate and speech intelligibility [18]. Similarly, Rusz et al examined the effects of DBS stimulation on speech fluency, speech intelligibility, and dysarthria in 19 patients with various types of dystonia who received bilateral GPi DBS [19]. However, both studies examined patients off and on stimulation during the same day (in 45-minute or 2-hour periods between off and on settings). Furthermore, they reported only on the effects of DBS stimulation on patient voice and speech.
The progression and change in the voice and speech of patients implanted with bilateral DBS for primary and vocal dystonia has not been investigated previously, to the best of our knowledge. Review of the few long-term follow-up studies supports that patients with dystonia can experience delayed improvements in speech intelligibility for several years following surgery [20,21]. The purpose of this study was to more thoroughly characterize changes in voice and speech 6 and 12 months post-DBS bilateral implantation, using auditory perceptual analyses.
1.2. METHODS
1.2.1. Participants
Recordings of 14 patients with dystonia (7 male and 7 female) were obtained from two fellowship-trained movement disorder specialists in the Department of Neurology at Wake Forest Baptist Health. A retrospective chart review was completed. Inclusion criteria were: 1) patients with a diagnosis of primary dystonia made by a fellowship-trained movement disorder neurologist; 2) patients who received bilateral DBS for medically refractory primary dystonia; 3) patients who were 18–85 years of age; and 4) patients who had a pre-DBS video recording and at least one post-DBS video recording. Exclusion criteria were: 1) patients with a diagnosis of secondary dystonia; 2) patients who were younger than 18 or older than 85 years of age.
1.2.2. Study Design
This study was approved by the Institution Review Board (IRB00039291) at Wake Forest Baptist Medical Center. Clinical assessments and patient audio recordings were obtained pre-DBS, 6 months post-DBS, and/or 12 months post-DBS. These recordings were measured in an off-medication state for pre-DBS recordings and in an off-medication, on-stimulation state for post-DBS recordings. Four patients with DYT1-mutation positive disease, 6 patients with cervical dystonia, and 4 patients with generalized dystonia were included in the study. Prior to receiving DBS, 2 patients had dysarthria, 2 patients had laryngeal dystonia, 5 patients had both laryngeal dystonia and dysarthria, 4 patients had no perceptible neurological voice condition, and 1 patient lacked a pre-DBS voice/speech assessment (this patient was excluded from analyses). Patients underwent DBS programming using our standard of care protocol to optimize motor symptoms (not voice quality); these programming data were recorded (Table 1).
Table 1.
Last recorded stimulation parameters at 12-month post-DBS for the 10 patients with dystonia included in GRBAS and CGI-s analyses. A positive value for the mean change from 6 months to 12 months indicates an increase in stimulation parameter at the 12-month appointment.
| Bilateral GPi Stimulation Parameters | Median Frequency (Range of Frequency) (Hz) | Median Amplitude (Range of Amplitude) (V) | Median Pulse Width (Range of Pulse Width) (µsec) |
|---|---|---|---|
| Right | 135 (60 to 185) | 3.55 (2.1 to 4.2) | 140 (90 to 270) |
| Left | 135 (60 to 185) | 3.5 (2.2 to 4.7) | 150 (60 to 270) |
| Average change from 6 months post-DBS programming | 9.375 | 0.425 | 2.5 |
Following a standardized protocol, participants read from the standardized Rainbow Passage [22], sustained vowel phonation (i:), and/or spoke several connected sentences according to the level of their comfortable modal pitch and volume. Video recordings were obtained. The audio from the videos was then extracted to ensure only patient audio remained; all patient identifying information, including diagnosis, was then removed. Pre-operative recordings were defined as recordings from the patient pre-DBS implantation; post-operative recordings were defined as recordings of the patient obtained 6 and 12 months post-DBS implantation.
Ten of the 14 patients were analyzed at 6-month post-DBS; four patients were not included due to either insufficient audio for analysis or loss to follow-up. Six of these 10 patients as well as 1 additional patient were analyzed at 12-month post-DBS. Three of the 10 patients that were analyzed at 6-month post-DBS were lost to follow up and therefore could not be assessed at 12-month post-DBS.
1.2.3. Surgery
In Phase 1 of DBS surgery, all patients were bilaterally implanted with appropriate leads (Medtronic, Minneapolis, MN, Medtronic electrode 3389) in the GPi. One patient with severe cervical dystonia received bilateral implantation of the VIM and unilateral implantation of the right GPi. In Phase 2 (11 to 14 days after Phase 1), all patients were implanted and connected to a neurostimulator in the subclavicular area (unilateral Activa PC 37601=4, unilateral Activa SC 37603=1, unilateral Activa RC 37612=2, unilateral Kinetra=2, bilateral Activa PC 37601=1, bilateral Activa SC 37603=4). Before DBS programming, patients underwent post-operative computerized axial tomography (CAT) to confirm lead locations. All leads were in the intended targets.
1.2.4. Clinical Evaluation
Burke-Fahn-Marsden Dystonia Rating Scale:
As part of routine clinical care, patients were evaluated for the severity of motor symptoms using the Movement (M) and Disability (D) subsections of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-M/D) [23]. Patients were rated pre-operatively, immediately post-operatively, and 6 months post-DBS implantation.
Perceptual Ratings of Voice and Speech Intelligibility
GRBAS
Raters were blinded to patient diagnosis as well as the timing of the recording in terms of whether it was before or after surgery. Blinded raters rated the audio recordings separately from each other. Two laryngologists and one speech language pathologist were blinded raters for the GRBAS assessment. Raters were not aware if the audio was pre-DBS or post-DBS. All recordings were randomly presented to the raters, with four recordings randomly repeated to assess intra-rater reliability. The raters listened to each consecutive recording and assessed each voice using the Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) [24] scale. This scale was selected to subjectively assess changes in voices of the patients at each time point. Each rater graded each audio recording from 0–3 (0 indicating normalcy, 3 indicating most affected) for each GRBAS scale category.
CGI-s
Blinded raters again rated the audio recordings separately from each other. Two laryngologists and three speech language pathologists served as blinded raters for the CGI-s assessment. The same raters for the GRBAS portion of the study served as blinded raters for the Clinical Global Impression Scale of Severity (CGI-s) [25]; in addition, two other speech language pathologists were introduced as raters. The CGI-s is a numerical scale from 0–7 (with zero indicating normalcy) designed for clinicians to rate the severity of a specified symptom, which in this case was dysarthria. This scale and the GRBAS scale were used to subjectively assess changes in severity of speech intelligibility at each time point.
Inter-Rater and Intra-Rater Reliability
We tested inter-rater reliability by comparing scores of all three blinded raters for each audio recording. Additionally, to test the ability of the blinded raters to reproduce the same score for a given recording, four audio recordings were randomly selected to be repeated within the group of the audio recordings for the blinded raters to score. Lastly, to verify reproducibility of the CGI-s scale scores between raters, we compared scores assigned by the blinded raters for each audio recording.
Statistical Analysis
The statistical software used for all statistical analysis was SAS version 9.4. To test whether the BFMDRS-M/D scores changed significantly over time, a mixed model was fitted separately for the BFMDRS-M data and then again for the BFMDRS-D data. A repeated measures analysis of variance model, including the terms MONTH and RATER, was used to explore changes in CGI-s scores over time and to evaluate changes over time among the GRBAS categories. Kappa statistics and the intraclass correlation coefficient were calculated using Cohen’s kappa coefficient test to assess inter-rater reliability. Intra-rater reliability was assessed using the intra-class correlation coefficient and descriptive statistics.
1.3. RESULTS
Patients age ranged from 19 to 82 years old (mean age 62.6 ± 16.3). Bilateral GPi DBS significantly improved BFMDRS-M/D scores from baseline to directly following surgery (Table 2). Motor and Disability portions of the BFMDRS showed significant differences in scores from pre-DBS to directly post-DBS and from pre-DBS to 6-month post-DBS, but not from directly post-DBS to 6-month post-DBS.
Table 2.
Clinical profile of patients with dystonia. Patients 1–11 were the total number of patients included in GRBAS and CGI-s analyses; Patients 1–10 comprise data for the 6 months post-DBS time point and patients 1–6 and 11 comprise data for the 12 months post-DBS time point. Patients 12–14 either did not have sufficient audio for analysis or were lost to follow up.
| Patient | Age | Sex | Disease Type | Disease duration (years) | BFMDRS–Motor/Disability Score Pre-DBS | BFMDRS–Motor/Disability Score directly post-DBS & 6 months post-DBS | % Improvement in BFMDRS–Motor/Disability Score |
|---|---|---|---|---|---|---|---|
| 1 | 71 | Female | Cervical dystonia | 30 | 28/12 | Post-op: 10/5 6 months: 5/2 |
82/83 |
| 2 | 40 | Male | DYT1 Positive dystonia | 35 | 56/15 | Post-op: 10/8 6 months: 6/2 |
89/87 |
| 3 | 61 | Male | DYT1 Positive dystonia | 20 | 39/13 | Post-op: 8/4 6 months: 5/3 |
87/77 |
| 4 | 80 | Female | Cervical dystonia | 37 | |||
| 5 | 61 | Male | DYT1 Positive dystonia | 40 | 31/15 | Post-op: 7/6 6 months: 4/2 |
87/87 |
| 6 | 82 | Female | Generalized dystonia | 15 | 43.5/18 | Post-op: 8/5 6 months: 6/3 |
83/86 |
| 7 | 73 | Female | Cervical dystonia | 12 | 22/5 | Post-op: 12/3 6 months: 10/2 |
55/60 |
| 8 | 71 | Male | Cervical dystonia | 28 | 43.5/18 | Post-op: 8/5 6 months: 6/3 |
83/86 |
| 9 | 53 | Female | DYT1 Positive Dystonia | 20 | 40/25 | Post-op: 35/20 6 months: 33/20 |
|
| 10 | 19 | Male | DYT1 Positive dystonia | 10 | 60/22 | Post-op: 11/9 6 months: 9/9 |
85/59 |
| 11 | 63 | Male | Generalized dystonia | 40 | 46/22 | Post-op: 36/18 6 months: 34/18 |
26/18 |
| 12 | 70 | Female | Cervical dystonia | 25 | 28/13 | Post-op: 6/3 6 months: 5/2 |
83/81 |
| 13 | 35 | Male | Generalized dystonia | 8 | 34.5/16 | Post-op: 8/5 6 months: 6/3 |
83/81 |
| 14 | 46 | Female | Cervical dystonia | 5 | 7/1 | Post-op: 4/1 6 months: 19/1 |
-43/0 |
| Mean (stdev) | Mean (stdev) | Mean(stdev) | |
|---|---|---|---|
| Measure | Pre-DBS | 6-mo post-DBS | 12-mo post-DBS |
| BFMDRS-M | 36.7 (3.7) | 11.4 (3.7) | 10.4 (3.7) |
| BFMDRS-D | 13.9 (1.8) | 6.4 (1.8) | 5.3 (1.8) |
| Measure | Pre-DBS v. post-DBS p-value | Pre-DBS v. 6-mo post-DBS p-value | Post-DBS v. 12-mo post-DBS p-value |
|---|---|---|---|
| BFMDRS-M | <.0001 | <.0001 | 0.8300 |
| BFMDRS-D | 0.0003 | <.0001 | 0.5176 |
1.3.1. GRBAS Perceptual Rating of Voice
Grade, Roughness, and Strain declined significantly from pre-DBS to 12-month post-DBS (p<0.0001, p=0.0043, p<0.0001, respectively). Asthenia increased from pre-DBS to 6-month post-DBS (p=0.0022) and then declined significantly from 6-month post-DBS to 12-month post-DBS (p=.0170), but did not significantly differ between pre-DBS and 12-month post-DBS time points (p=0.6271). Breathiness did not significantly change over time (p=0.1765). Among the 10 patients with dystonia, pre-DBS scores did not significantly improve in any GRBAS category compared to 6-month post-DBS (Table S1–S5), and 2–4 patients worsened compared to their pre-DBS GRBAS score in each category (Figure 1). Between 5 and 7 patients had the same GRBAS scores in each category pre-DBS and 6-month post-DBS. However, of the 7 patients with pre-DBS and 12-month post-DBS data, no patient worsened in any category and most improved compared to their pre-DBS score in each category (Figure 2). Progressive changes in individual patients’ scores for each GRBAS category are shown in Figure 3.
Figure 1:
GRBAS scores for each of 10 patients with dystonia 6 months post-DBS. Change in Asthenia score significantly improved (p=0.0022). Change in Grade (p=0.6694), Roughness (p=0.1653), and Strain (p=0.1638) scores did not significantly improve. Breathiness was not tested because it did not significantly change over time. Worsening in score was defined as 0.5+ unit increase in GRBAS score pre-DBS compared to 6 months post-DBS. Improvement in score was defined as 0.5+ unit decrease in GRBAS score pre-DBS compared to 12 months post-DBS.
Figure 2:
GRBAS scores for each of 7 patients with dystonia 12 months post-DBS. Change in GRBAS scores for seven patients with dystonia at 12 months post-DBS. Grade (p=0.0211), Roughness (p=0.0011) and Strain (p=0.0035) were significantly improved. Asthenia (p=0.6271) did not significantly improve and Breathiness was not tested because it did not significantly change over time. Worsening in score was defined as 0.5+ unit increase in GRBAS score pre-DBS compared to 6 months post-DBS. Improvement in score was defined as 0.5+ unit decrease in GRBAS score pre-DBS compared to 12 months post-DBS.
Figure 3:
Changes in GRBAS and CGI-s scores for each patient following DBS. For 6 months post-DBS data, n=10; for 12 months post-DBS data, n=7. Patients with overlapping scores are shown as one line. For detailed individual GRBAS and CGI-s scores, please refer to the Supplemental Material.
1.3.2. CGI-s Rating of Speech Intelligibility
Ten patients with dystonia were included in the pre-DBS compared to 6-month post-DBS CGI-s study, and 7 patients with dystonia were included in the pre-DBS compared to 12-month post-DBS CGI-s study (Figure 4). CGI-s scores significantly decreased over time (p=0.0081), from 6-month to 12-month post-DBS (p=0.0202), and pre-DBS to 12-month post-DBS (p=0.0022) (Table S6). Speech intelligibility improved when pre-DBS and 6-month post-DBS CGI-s scores were compared, but it was not statistically significant (p=2312). Statistically significant reductions in CGI-s scores are not necessarily clinically significant; however, no patient experienced an increase in CGI-s score or, by extension, in dysarthria over time post-DBS. The progressive change in CGI-s score for each patient is shown in Figure 3.
Figure 4:
Long-term improvement in CGI-s scores post-DBS in patients with dystonia. Pre-DBS scores were significantly improved compared to 12 months post-surgery (p=0.0022) and when comparing 6 months post-surgery to 12 months post-surgery (p=0.0202). Pre-DBS scores also improved compared to 6 months post-DBS, although it was not a significant improvement (p=2312). Error bars indicate standard errors of the least squares mean.
1.3.3. Inter-rater and Intra-rater Reliability
Kappa statistics were used to find the degree of agreement between raters for Grade, Roughness, Breathiness, Asthenia, and Strain. It was found that Grade and Strain had the highest inter-rater agreement ratings (κ=0.84 and κ=0.71 respectively), while Asthenia had the lowest (κ=0.30). Mixed model analyses to determine effects of time and rater on CGI-s yielded an intraclass correlation coefficient of 0.78 (1 indicates perfect agreement between raters). This shows that variability in values was due mostly to differences between subjects, not rater differences. For intra-rater reliability, each participant was rated twice by the same rater on five characteristics (“pre” and “post”). From these repeated ratings pre-DBS to 6 and 12 months post-DBS. No single characteristic was more likely to be associated with disagreement.
1.3.4. Patient Speech and Voice Outcomes
Voice and speech outcomes for the 7 patients with pre-DBS and 12-month post-DBS data are shown in Table 3. While the voice and speech outcomes for patients at 6-month post-DBS did not show significant improvement in any GRBAS category or CGI-s analysis, all patients with dystonia included in the 12-month post-DBS analysis experienced improvement in at least one GRBAS category and CGI-s speech score. However, only the Grade, Roughness, and Strain categories showed statistically significant improvements. No single type of primary dystonia was associated with greater voice and speech improvement.
Table 3.
12-month post-DBS voice and speech outcomes, pre-DBS voice/speech diagnoses, and type of dystonia for the 7 patients with dystonia with pre-DBS and 12-month post-DBS analyses. Note: Patient numeric identifiers are consistent between Tables 1 and 2 (i.e. Patient 6 in Table 1 corresponds to Patient 6 in Table 2).
| Patient | Diagnosis | Pre-DBS voice and/or speech diagnosis | Voice improvement in specific GRBAS categories* | Speech improvement in CGI-s rating# |
|---|---|---|---|---|
| 1 | Cervical dystonia | No perceptible neurological voice condition | Grade, Roughness, Asthenia, Strain | No change |
| 2 | Generalized dystonia | Laryngeal dystonia and dysarthria | Roughness, Strain | 56.5% Improvement |
| 3 | DYT1-positive dystonia | Laryngeal dystonia and dysarthria | Roughness | 84.8% Improvement |
| 4 | Cervical dystonia | Laryngeal dystonia and dysarthria | Breathiness, Asthenia, Strain | 57.1% Improvement |
| 5 | DYT1-positive dystonia | Laryngeal dystonia | Grade, Roughness, Strain | 57.1% Improvement |
| 6 | Generalized dystonia | Dysarthria | Roughness, Strain | Increase in dysarthria observed |
| 11 | Generalized dystonia | Laryngeal dystonia and dysarthria | Grade | 70% Improvement |
Improvement in each GRBAS category score was defined as 0.5+ unit decrease in GRBAS score pre-DBS compared to 12-month post-DBS.
Improvement in CGI-s score was calculated as average 12-month post-DBS CGI-s speech rating divided by pre-DBS CGI-s speech rating multiplied by one hundred.
1.4. DISCUSSION
To our knowledge, no other reports have studied effects of bilateral GPi DBS on voice quality and speech intelligibility in patients with dystonia at multiple time points post-DBS using perceptual analysis of voice. We found that bilateral GPi DBS resulted in significantly improved speech and voice quality of patients with primary dystonia 12 months post-DBS, based on perceptual analysis of patient voice and speech using blinded raters. This significant improvement was not observed 6 months post-DBS, indicating that there is a potentially delayed beneficial effect for patients with dystonia, particularly in the neural pathways associated with speech and voice production and control.
The quality and magnitude of voice and speech using perceptual analysis of voice improvement post-bilateral GPi DBS implantation has not been studied in patients with primary dystonia. Although studies in the field of otolaryngology have examined effects of stimulation parameters on voice and speech in patients with dystonia, to our knowledge none have compared multiple post-DBS time points using the methods in this study.
It is thought that patients with dystonia have abnormal plasticity in their motor learning, which leads to abnormal sensorimotor assimilation [26,27]. Attempted eradication of this abnormal plasticity, as with DBS implantation, may have a greater effect on motor dysfunction at later time points evaluated [19,28] secondary to corrupt motor memories already established and thus difficult to eradicate. These deeply embedded motor memories may explain why DBS implantation sometimes results in delayed improvement in patient motor symptoms [29].
Most previous studies largely focused on patients with PD or ET and showed no effect, or even worsening, of speech intelligibility after DBS; some report reduced benefit for speech [30]. The few previous reports that examined patients with dystonia either focused on dysarthria, did not use perceptual analysis of voice to compare longitudinal effects of DBS on voice and speech, or secondarily reported on voice improvement in the context of focal dystonias. Vidailhet et al followed 22 patients with primary generalized dystonia over 3 years and used the two subsections of the BFMDRS scale where the clinician rates patients’ mouth movements, speech, and swallowing abilities. They reported that speech and swallowing of patients with dystonia did not significantly improve following GPi DBS [31]. In a recent study, Rusz et al examined the effect of stimulation in 19 patients with dystonia at a single time point after bilateral GPi DBS with the average time post-DBS being 3.2 (SD 1.9) years. Specific speech and voice concerns, such as an increase in dysfluent words, were reported when stimulation was on; however, they did not note if any patients had speech or voice conditions, such as laryngeal dystonia, prior to the study [19]. Another report examined long-term outcomes of patients implanted with bilateral VIM for essential tremor and adductor spasmodic dysphonia as a secondary complaint. Of 10 patients with concurrent laryngeal dystonia, two showed no benefit and two worsened (six were not reported on) [32].
A few case reports have described voice improvement after bilateral GPi DBS. Risch et al examined the effects of on/off DBS stimulation in 15 patients with cervical dystonia; they describe one patient with laryngeal dystonia who benefited after bilateral DBS implantation to the GPi for primary cervical dystonia [18]. Similarly, Mure et al reported voice improvement following bilateral GPi DBS in a patient with DYT6 dystonia and concurrent laryngeal dystonia [33].
The present study has several limitations. Dystonia is a rare disorder, and only a small percentage of this population undergoes DBS implantation. This makes prospective studies on dystonia challenging. As a result, our study had the limitations of a retrospective design. Regardless, our study is among the larger studies of DBS in dystonia which have looked at speech and voice as outcome measures at multiple time points post-bilateral DBS in a blinded fashion. In the original cohort of 14 patients, 10 patients were analyzed at 6-month post-DBS. 6 out of these 10 patients plus 1 additional patient were analyzed at 12-month post-DBS. The number of patients lost to follow-up is a study limitation and could introduce bias into our results. However, we minimized this potential bias by ensuring that all patients received the same evaluation and assessment, and by using inter-rater and intra-rater analyses. Another limitation is the fact that audio recordings were obtained during patient visits in the neurology clinic. However, the quality of these audios was satisfactory and allowed us to gather data that support our prospective study of how voice and speech are affected post-DBS in patients with dystonia. In our patients with dystonia, we are now prospectively collecting Cepstral Spectral Index of Dysphonia (CSID) [34] data and patient-reported voice quality of life measures pre-DBS and post-DBS implantation with the standardized, validated Voice Handicap Index – 10 (VHI-10) [35].
1.5. CONCLUSIONS
Our study demonstrates that GPi DBS can improve voice and speech in patients with primary dystonia up to one year following implantation. The fact that the improvement in speech/voice was not significant 6 months post-DBS suggests a delayed treatment effect, a phenomenon commonly seen in motor symptoms of dystonia following GPi DBS. However, the improvement in speech/voice was not universal; therefore, we need further studies to identify prognostic factors for speech/voice in patients who under GPi DBS, specifically in placement of DBS electrodes and identification of voice and speech pathways in focal laryngeal dystonia. With further studies and fine-tuning of the techniques involved with electrode placement, DBS can potentially be expanded as a treatment option for focal laryngeal dystonia.
Supplementary Material
ACKNOWLEDGEMENTS:
We acknowledge statistical assistance from Julia Rushing and editorial assistance from Karen Klein, both of the Wake Forest Clinical and Translational Science Institute supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR001420 (PI: McClain). We also acknowledge help from Omar Saeed, MDa who assisted with collecting the BFMDRS scores for the subjects included in our study, and Kevin Cunningham, CCC-SLPb who assisted with the blinded ratings of the audio obtained from our subjects.
Funding: L.L.M. received statistical support through a grant from National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR001420 (McClain, PI). This funding organization did not contribute to the design or conduct this study.
ABBREVIATIONS:
- DBS
Deep Brain Stimulation
- GPi
Globus Pallidus Interna
- STN
Subthalamic Nucleus
- VIM
Ventral Intermediate nucleus
- BFMDRS
Burke-Fahn-Marsden Dystonia Rating Scale
- CGI-s
Clinical Global Index of Severity
AUTHOR VITAES:
Mary Finger, BS is a master’s student in the BS-MS 4+1 program in Neuroscience at the Wake Forest University Graduate School. She received a BS degree from Wake Forest University in 2018. Her current interdisciplinary thesis work is based in the Neurology and Otolaryngology-Head & Neck Surgery department at the Wake Forest Baptist Medical Center (WFBMC) and focuses on maximizing movement disorder patients’ voice, speech, and swallowing outcomes following deep brain stimulation (DBS). Her research interests include DBS, dystonia, astrocytes, and NG2+ cells.
Mustafa Siddiqui, MD, FAAN is an Associate Professor of Neurology & Neurosurgery and Medical Director of the DBS program at WFBMC. He completed his neurology residency at Drexel University and then completed a Fellowship in movement disorders at the University of Florida. He is a Fellow of the American Academy of Neurology and American Neurological Association and a member of Movement Disorder Society. He is on the Expert Panel of Best Doctors in America, has been Principal Investigator in many clinical trials for Parkinson’s disease, and has published in peer reviewed journals.
Amy Morris, MM, MA, CCC-SLP is the Outpatient Manager of Speech-Language Pathology at WFBMC. She is a licensed speech-language pathologist and singing voice specialist who works with voice and upper airway disorders, along with issues affecting professional voice users. Previously, she worked as a voice pathologist at Ohio ENT in Columbus, OH. She completed her clinical fellowship in voice and swallowing at the Emory Voice Center in Atlanta, GA from 2005–2006, completed her MA in Speech and Hearing Sciences at Indiana University, and MM in vocal pedagogy at East Carolina University.
Kathryn Ruckart, MS, CCC-SLP is a speech-language pathologist specializing in the treatment of voice disorders at WFBMC. Kathryn received her BA from UNC Chapel Hill and an MS degree in communication sciences and disorders from East Carolina University. Her primary clinical interests include care of the professional speaking voice, rehabilitation of functional voice disorders, and behavioral management of Paradoxical Vocal Fold Motion (PVFM) and irritable larynx syndrome. She holds a license from the North Carolina Board of Examiners for Speech-Language Pathology and Audiology and a Certificate of Clinical Competence in Speech-Language Pathology from the American Speech-Language-Hearing Association.
Dr. S. Carter Wright graduated from Boston University School of Medicine and completed an internship in General Surgery and a residency in Otolaryngology Head and Neck Surgery at Mount Sinai Hospital in New York. He then completed a fellowship in Laryngology at Wake Forest. He is now an Associate Professor at WFBMC. His clinical and research interests include care of the professional voice, management of the critical airway, recurrent respiratory papilloma, and assessment and care of the voice challenges faced by patients with spasmodic dysphonia and Parkinson’s disease.
Dr. Ihtsham U. Haq completed a Neurology residency at Georgetown University, and a Movement Disorders fellowship at the University of Florida. His fellowship included training in medical and surgical treatment of movement disorders, including DBS surgery. He has been a faculty member in the Department of Neurology at WFBMC since 2009 and treats patients with Parkinson’s disease, essential tremor, dystonia, and Tourette syndrome. His main research interest is the nonmotor functions of the basal ganglia. He is funded for his research into DBS, Alzheimer’s disease, and rapid-onset dystonia parkinsonism.
Lyndsay Leigh Madden, DO, is an Assistant Professor of Otolaryngology at WFBMC. She earned her DO degree from Kentucky College of Osteopathic Medicine in 2009, and then completed an otolaryngology residency at Ohio University. She then completed a fellowship in Laryngology and Care of the Professional Voice at the University of Pittsburgh Voice Center,. Dr. Madden is a board-certified otolaryngologist whose scope of practice encompasses disorders affecting voice, breathing, coughing, and swallowing, and other throat symptoms. Her current research interests lie in patient safety and quality improvement, neurologic disorders of the larynx, laryngeal dystonia, and swallowing disorders. She has given many lectures at the local, regional, state, and national level in her field. Dr. Madden also serves on several national committees in the American Academy of Otolaryngology, and on the Editorial Boards for the Journal of Voice, ABEA, and AOCOO-HNS.
Footnotes
Presented at the American 139th Annual Meeting of the American Laryngological Association at the Combined Otolaryngology Spring Meetings, National Harbor, Maryland, United States of America, April 18–22, 2018.
Conflicts of Interest: The authors have no other funding, financial relationships, or conflicts of interest to disclose.
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