Assessment of Laryngopharyngeal Sensation in Adductor Spasmodic Dysphonia
Condition: Spasmodic Dysphonia; Adductor Spasmodic Dysphonia; Voice Disorders
MeSH terms: Dysphonia; Hoarseness; Voice Disorders
Study type: Interventional

Summary: 
      Study investigators have completed a study testing laryngopharyngeal sensation at specific
      laryngopharyngeal subsites using a novel buckling force aesthesiometer in a series of 22
      healthy adults at this institution. Investigators would like to use the same device apparatus
      to evaluate laryngopharyngeal sensation in patients with laryngopharyngeal disorders, such as
      adductor spasmodic dysphonia. This study will use a tested laryngopharyngeal aesthesiometer
      to examine laryngeal sensation using calibrated tactile stimuli to determine differences in
      somatotopic perceptual strength maps of laryngopharyngeal structures between patients with
      laryngopharyngeal disorders and healthy controls.
    

Detailed description: 
      Participant Recruitment Subjects with adductor type LD (AdLD) were identified and recruited
      by advertisements and by study clinicians at their institution. Advertisements were
      physically placed in the UCSF Voice and Swallowing Center clinic and were delivered
      electronically through the website of the National Spasmodic Dysphonia Association and to
      area LD ("spasmodic dysphonia") support groups.

      Adults greater than 18 years old with AdLD were included if they received a diagnosis
      established by a multi-disciplinary evaluation by a fellowship-trained laryngologist and
      voice-specialized speech-language pathologist. Subjects diagnosed by a physician outside of
      the study facility were evaluated in-person by a fellowship-trained laryngologist to confirm
      their eligibility for this study. All patients were required to have history of favorable
      response to intra-laryngeal botulinum toxin A (BtxA) treatment, as further demonstration of
      the correct diagnosis of ADLD. This was especially helpful for patients initially diagnosed
      outside of our center. Subjects with abductor or mixed type LD were not included in the
      present study due to their low incidence, but concurrent essential tremor (ET) of the vocal
      tract was accepted.

      Patients were also excluded if they had a history of: concurrent laryngeal diseases or
      conditions other than AdLD+/-ET; bleeding disorder or current anticoagulation use; head and
      neck radiation; active tobacco use; or drinking more than two alcoholic beverages per day. If
      laryngopharyngeal lesions and/or masses, impeding abnormal laryngopharyngeal structure(s), or
      excessive post-nasal drip were noted on laryngoscopy, then examination ceased, and patients
      were excluded. Prior to testing, subjects also completed symptom-specific patient reported
      outcome measures (PROMs), including: Reflux Symptom Index (RSI),18 Voice Handicap Index-10
      (VHI-10),19 Dyspnea Index (DI),20 Cough Severity Index (CSI),21 and Eating Assessment Tool-10
      (EAT-10).22 These PROMs are standardly collected as part of the routine clinical are for all
      patients undergoing evaluation at this center and are reported herein for holistic
      characterization of these subjects but not intended as a reflection or measure of the
      severity of their AdLD. Lastly, to avoid any potentially confounding physical effects from
      the injection (e.g., vocal fold edema), no testing was performed in the two weeks immediately
      following BtxA treatment. For patient convenience and to facilitate maximal enrollment,
      patients were allowed to undergo testing at any point outside of this post-injection window,
      although the majority pursued testing immediately prior to a BtxA injection on the same day.

      Healthy controls were defined as adults between 18 and 85 years of age without
      laryngopharyngeal disease and were subject to the same screening and exclusion criteria.23
      Additionally, controls were excluded if they had abnormal patient reported outcome measures
      (i.e. Reflux Symptom Index (RSI) score> 13, Eating Assessment Tool-10 (EAT-10) score>2, or
      Voice Handicap Index-10 (VHI-10) score> 11).

      Aesthesiometer Device As outlined in previous work, modified nylon monofilaments fixed to the
      end of 5-French open lumen catheters were utilized to deliver tactile stimuli to
      laryngopharyngeal subsites.12 The Food and Drug Administration (FDA) has previously ruled the
      aesthesiometer to be a Nonsignificant Risk (NSR) Device Study (Q190371/S001). Three nylon
      monofilament sizes (6-0, 5-0, 4-0) were cut to a calibrated length of 30 mm to deliver three
      distinct tactile stimuli of increasing strength, known as buckling-force. The 6-0, 5-0, and
      4-0 monofilaments deliver an increasing mean force of 0.03 g, 0.11 g, and 0.30 g,
      respectively.12 An intermediary strength "4.5-0" monofilament was created by using a 5-0
      monofilament of 25mm length, which has been demonstrated to have a mean buckling force of
      0.19 g.23 During testing, the monofilaments were passed through the working channel of a
      flexible ENF-VT2 laryngoscope (Olympus America, Inc., Center Valley, PA) to allow for direct
      visualization and concurrent stimulation of laryngopharyngeal subsites.

      Laryngopharyngeal Sensory Evaluation All subjects underwent a standard protocol for
      laryngopharyngeal sensory evaluation. This has been described in detail previously but
      briefly reviewed again here.12,13 Prior to testing, subjects were screened for any recent
      changes in conditions affecting voice and swallowing to ascertain subjects-maintained
      inclusion criteria. Three investigators executed laryngopharyngeal testing: 1) one to operate
      the laryngoscope; 2) one to maneuver the aesthesiometer monofilament; and 3) one to monitor
      testing, record subjective patient response, and observe cough/gag/swallow responses.

      An investigator then examined both nasal passageways with a nasal speculum, selecting the
      more patent pathway for laryngoscope insertion. The more patent nasal passageway was
      topically anesthetized with cottonoid pledgets soaked in a 50/50 mixture of 4% lidocaine
      hydrochloride and neosynephrine. The cottonoid pledgets were compressed to remove excess
      liquid to avoid unintentional spillage posteriorly to the nasopharynx and potentially larynx,
      and left in place for five minutes.

      The channeled laryngoscope was then inserted along the inferior meatus towards the posterior
      nasopharyngeal wall. The 6-0 monofilament was pressed against the posterior nasopharyngeal
      wall and swiftly removed to establish a perceptual strength of "1". If subjects were
      insensate to this stimulation, monofilament size was incrementally increased (i.e., 5-0,
      4.5-0, and 4-0) until the stimulus was perceived, to establish this internal anchor. As per
      the validated, standardized protocol, all AdLD participants were stimulated on the left,
      allowing maximal visualization of the vocal folds during testing due to camera configuration
      of the flexible laryngoscope. Only four controls were stimulated on the right side, during
      earliest phases of testing.

      Starting with the 6-0 monofilament, the lateral pyriform sinus (LPS) was presented with the
      planned stimulus, followed by the aryepiglottic fold (AEF) and the false vocal folds (FVF).
      (Figure 1) Participants were instructed to raise their hand when the stimulus was detected,
      and then were asked by the study team to report a perceptual strength "score," in comparison
      to the nasopharyngeal anchor strength of 1. LAR response was observed and recorded by the
      study team. A negative response was defined as a lack of LAR to two appropriate stimuli. Gag
      or cough response to stimuli delivery were also recorded, assuming a positive LAR during
      these observations.

      The LPS and AEF were tested in order of increasing stimulus: 5-0, 4.5-0 and 4-0
      monofilaments. The false vocal folds (FVF) were tested last, in the same order of increasing
      monofilament strength. Testing of FVF terminated after the first observed LAR given site
      sensitivity, assuming positive responses would also be present for increased monofilament
      strength.

      LAR Assessment Confirmation of LAR was determined using post-hoc frame-by-frame analysis of
      video recordings. Unilateral or bilateral vocal fold adduction following stimulus delivery
      was recorded as a positive response. Upon review, stimuli were excluded if they did not
      produce 10-30% monofilament buckling (as observed by the reviewer), were entrapped by saliva,
      or could not compress orthogonally to the mucosal surface. Additionally, if line of sight of
      visualization of vocal fold adduction was obstructed or confounded by phonation, the stimuli
      were excluded. All stimuli were reviewed by one study investigator with 30% of stimuli
      reviewed by a blinded second reviewer. Disagreements were reconciled by a blinded third
      reviewer.
    

Intervention name(s): Sensation testing
Intervention type(s): Device
Intervention description(s): Sensation testing tactile aesthesiometer.
Intervention model: Single Group Assignment
Intervention model description: Cottonoid pledgets soaked in 4% lidocaine and neo-synephrine will be placed on this side. The pledgets will be kept in place for 5 minutes to allow adequate decongestion and anesthetization. The aesthesiometer will be placed through the 2.0 mm working channel of the Olympus Corporation (Tokyo, Japan) ENF-VT2 channeled flexible video rhinolaryngoscope with a 4.9 mm outer diameter. The flexible laryngoscope and aesthesiometer assembly will then be advanced into the pharynx and positioned for target testing. The operator field of view will be adjusted in the craniocaudal axis to optimize visualization of the stimulation target, monofilament tip, and both vocal folds to assess for a stimulation evoked LAR response. The monofilament will then be advanced to within several mm of the target laryngopharyngeal subsite and subsequently applied orthogonally until it buckled by 10-30%, followed by quick retraction to assess for triggering of the rapid LAR response.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: throat sensation