Quantifying Stridor Associated with Parkinsonism and Deep Brain Stimulation—A Case Report

We present a patient with a diagnosis of Parkinson's disease (PD) with an atypical presentation of stridor responsive to medication. The patient was treated with subthalamic nucleus (STN) deep brain stimulation (DBS) for medically refractory motor symptoms. The stridor deteriorated following DBS, and novel parameter adjustments were used to improve it. Laryngoscopy was performed before and after adjustment but not in each test condition for reasons of patient comfort. A laryngograph1 was instead used to provide an objective measure of vocal fold closure and stridor during adjustment along with a perceptual speech rating—the DAB scale.2 Stridor is a recognizable harsh and high pitched irregular inspiratory sound3 associated with impaired vocal fold abduction. Although cases have been reported,4 it is uncommon in PD and raises the suspicion of multiple system atrophy (MSA).5 A 54-year-old male with a history of parkinsonism presented initially with L-sided tremor, reduced arm swing, and shoulder pain. He was diagnosed with PD and treated with levodopa (l-dopa) and a dopamine agonist. At 10 years after onset, he was assessed for DBS due to medically refractory motor fluctuations and dyskinesia (Unified Parkinson's Disease Rating Scale, Part III [UPDRS-III] 32 off and 12 on). At this time, while inspiration was markedly audible, the stridor was not present in speech. Improvements in respiration and phonation were responsible for the higher on medication speech score (off medication DAB score, 28/42; on medication DAB score, 35/42). A history of mild stridor was reported (4 year), raising the suspicion of MSA. No evidence of autonomic dysfunction or imaging features of MSA were identified, and he had a sustained motor response to l-dopa. The patient reported that the stridor was partially responsive to l-dopa. He was treated with bilateral STN-DBS with a Boston Gevia device (Boston Scientific, Ireland), with a good motor response (UPDRS-III reduction of 50% with stimulation in the off medication state) and a reduction in motor fluctuations. Following DBS, the stridor became audible on exertion and intrusive in speech. At night, the stridor was audible but did not interrupt his sleep. Laryngoscopy 6 months after DBS found a maximum abduction of 4 to 5 mm and at 9 months 2.5 mm, after which tracheostomy was discussed. Due to the stridor's responsiveness to medication, stimulation adjustment was attempted to prevent or delay a tracheostomy. Our group previously demonstrated how novel stimulation techniques incorporating short pulse width and directional stimulation can ameliorate adverse effects, including stimulation-induced dysarthria and dyskinesia, and pyramidal side effects.6 A systematic monopolar review aiming to reduce stridor while maintaining motor function was carried out using both conventional (60 μs and 130 Hz) and novel approaches including frequency modulation, the use of shorter pulse width (30 μs), and directional screening at the vertical level of the chronically used contacts. Stridor severity was assessed in the context of speech after exertion. The following 4 conditions were tested: (1) off medication/OFF stimulation (off–OFF), (2) on medication/OFF stimulation (on–OFF), (3) on medication/ON baseline settings (on–BL), and (4) on medication/ON optimized settings (on–OP). A 6-week follow-up assessment was carried out (on–OP–CHRONIC) on optimized parameters. Baseline STN-DBS settings were of a standard ring mode configuration: 2.1 mA, −60 μs, and 130 Hz at contacts 2-3-4 and 10-11-12. The optimized settings were 5.9 mA, 30 μs, 79 Hz bilaterally at segmental contacts 3 at the left STN and 11,12 (50% each) at the right STN. UPDRS-III scores on stimulation before and after optimization (off/on medication) were 28/18 and 25/17, respectively. The impact of stimulation was quantified with baseline settings (on–BL) and subsequently optimized settings using short pulse width and directional stimulation (on–OP). Audio recordings are available as supplementary files (Audios S1–S3). Perceptual speech scores improved with medication (see Table 1). Although stridor remained intrusive, vocal fold irregularity (IFx%) decreased with medication (see Table 1) in regions indicative of high-frequency stridor. With optimized stimulation settings, perceptual speech scores improved with more precise, scaled, swift articulation as exemplified by decreased reading duration, and IFx reduced further (see Table 1), with high-frequency stridor all but absent (Fig. 1). Voice quality (mean, Qx%) also improved, reflecting a greater mean duration of closure throughout the vocal fold cycle. At the 6-week review (on–OP–CHRONIC), benefits to speech persisted and stridor improved. The patient confirmed improvement yet felt his voice was higher. Modal frequency (F0) was found to be elevated. Repeat laryngoscopy following optimization revealed the glottis to have increased to 7 mm. This was sustained for 10 months following the initial adjustment but ultimately declined, eventually necessitating tracheostomy placement. We report a patient with l-dopa- and STN-DBS-responsive parkinsonism who exhibited worsening stridor following DBS that responded to stimulation adjustment. The laryngograph may be a useful tool in the assessment of stridor and its impact on the irregularity of voice. The increase in mean modal pitch (F0) and shift to periodic stridor (Fig. 2) points to increased laryngeal tone in the optimized stimulation. In an analysis of stridor in MSA,3 increased periodicity was associated with enhanced laryngeal tone and greater stenosis. For our patient, the periodic stridor was accompanied by a wider glottis after adjustment and at the 6-week review; however, this did not persist. Although the mechanisms underlying stridor in parkinsonian disorders have not been fully elucidated, dystonia in the laryngeal adductor muscles has been a suggested cause. The worsening of stridor with conventional stimulation may represent a stimulation-induced side effect such as dystonia or hyperadduction of the vocal cords by corticobulbar tract stimulation7 and the use of novel stimulation techniques has been shown to alleviate these,6 corresponding to the improvement in stridor demonstrated in this case. Although there are previous reports of stridor being induced by STN-DBS in PD8, 9 to our knowledge this is the first reported case illustrating the utility of neuromodulation in partially alleviating stridor and delaying invasive measures and the usefulness of the laryngograph in quantifying stridor severity. (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique. T.G.: 1B, 1C, 2A, 2B, 3A V.D.: 1B 1C, 2A, 2B, 3A, 3B A.F.: 3A, 3B C.M.: 1A, 3B P.L.: 2C, 3B T.F.: 3B The authors confirm that the approval of an institutional review board was not required for this work. Verbal and written consent was obtained from the patient for the publication of this case study. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. P.L. has received honoraria and travel expenses from Medtronic and Boston Scientific for speaking at meetings. T.F. has received grants from National Institute of Health Research, The Michael J Fox Foundation, John Black Charitable Foundation, Cure Parkinson's Trust, Innovate UK, Janet Owens Research Fellowship, Rosetrees Trust, Van Andel Research Institute, and Defeat MSA. He has served on advisory boards for Peptron, Voyager Therapeutics, Handl therapeutics, Veeva Systems Inc, Living Cell Technologies, Bial, and Profile Pharma. He has received honoraria for talks sponsored by Bial, Profile Pharma, and Boston Scientific. The authors declare that there are no additional disclosures to report. Audio S1: A recording of stridor in the context of speech in the off medication and OFF stimulation condition (off–OFF). Audio S2: A recording of stridor in the context of speech in the on medication and OFF stimulation condition (on–OFF). Audio S3: A recording of stridor in the context of speech in the on medication and ON optimized stimulation condition (on-OP). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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