Clinical Assessment and Treatment of Individuals with Vocal (VT)

Julie Barkmeier-Kraemer, PhD, CCC-SLP Professor, ASHA-F University of Utah [email protected] Julie Barkmeier-Kraemer, PhD, CCC-SLP, ASHA-F Professor, Otolaryngology – Head and Neck Surgery Clinic Director, Voice Disorders Center Adjunct Faculty, Dept of CSD

DISCLOSURES: • Financial: • Affiliate instructor with royalties from MedBridge Inc for my online courses on vocal tremor • NIDCD funds my research on and vocal tremor (R01 DC016838) • Non-Financial: • ASHA: Member of SIGs 3, 12, 18 • Member of the NSDA Scientific Advisory Council Presentation Objectives:

1. Identify and describe the updated classification tremor criteria applied to vocal tremor and speech structures, 2. Describe clinical assessment approaches that enable improved differentiation between vocal tremor and laryngeal , and 3. Summarize treatment options for those with vocal tremor. Differential diagnosis of voice disorders “”

Focal Laryngeal Dystonia (Albanese et al, 2013)  Hyperkinetic movement disorder affecting 1 body part  “Sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both.”  Associated with onset or worsening specific to volitional speech activity (i.e. task specific)

 Affects 1 per 100,000 dystonia cases (Nutt, Muenter, Aronson, Kurland, Melton, 1988; Konkiewitz et al, 2002)  Less than 8% of those with SD have family members with dystonia (Xiao, Zhao, Bastian, et al, 2010; Hintze et al, 2017) Terminology: Classification is everything

2019: Laryngeal 1971- Dystonia present: (NIDCD Spasmodic workshop) 1959-1997: Dysphonia Spastic Dysphonia Simonyan K, Barkmeier-Kraemer J, Blitzer A, Hallett M, Houde JF, Jacobson Kimberley T, Ozelius LJ, Pitman MJ, Mark Richardson R, Sharma N, Tanner K; NIH/NIDCD Workshop on Research Priorities in Spasmodic Dysphonia/Laryngeal Dystonia. Laryngeal Dystonia: Multidisciplinary perspectives on terminology, pathophysiology, and research priorities. . 2021 Apr 15:10.1212/WNL.0000000000011922. doi: 10.1212/WNL.0000000000011922. Epub ahead of print. PMID: 33858994. LARYNGEAL DYSTONIA (LD) CHARACTERISTICS

Idiopathic onset (Schweinfurth, Billante, Courey, 2002; Adler, Edwards, Bansberg, 1997) Onset typically occurs during mid-life ages of 30- 50 years of age (Schweinfurth, et al, 2002) Women are more often affected than men (4:1 ratio) (Adler, Edwards, Bansberg, 1997; Schweinfurth, et al, 2002; Blitzer, 2010; Simonyan et al, 2021) Progression is steepest during first year and is chronic thereafter (Izdebski, Dedo, Boles, 1984; Brin, Blitzer, Stewart, 1998; Tanner et al, 2011) Normal vegetative voice function (Ludlow, 1995)  Laughing, Crying, Cough, Yawn, Whisper, Respiration SUBTYPES OF LD (using historical terms) TREMOR

• “An involuntary, rhythmic, oscillatory movement of a body part.” • One of the most common neurologic movement disorders. • Classified by clinical features/phenotypes and etiology.

(Crawford & Zimmerman, 2011; Louis, 2016; Elble, 2016; Bhatia et al, 2018) Tremor Features/Phenotypes • ACTION- INDUCED – Kinetic – Postural

http://www.examiner.com/article/it- s-not-an-earthquake-its-just- • RESTING parkinson-s-disease – Supported from gravity

http://gifsoup.com/view/1855096/pill Hallett, 2014; Weiss, 2016; Bhatia et al, 2018) -rolling-tremor.html Updated Criteria for Classification of Tremor Tremor Syndrome Clinical Features

• Age of onset • Family history Medical History • Temporal evolution • Exposure to drugs and toxins • Anatomical distribution of tremor (focal vs Tremor segmental vs generalized) • Activation condition (e.g. postural, kinetic, task characteristics specific, resting) • Frequency (i.e. rate; <4, 4-8, 8-12, >12 Hz) Associated • Signs of systemic illness • Neurologic signs Signs • Soft signs

• Electrophysiological tests Additional • Structural imaging • Receptor imaging laboratory tests • Serum and tissue biomarkers Etiology (Axis 2) Framework

Genetically Acquired Idiopathic defined

KEY POINTS: • A syndrome from Axis 1 map to Familial several etiologies. • Likewise, multiple syndromes can be associated with one etiology. • Clinical features offer the optimal Sporadic method for characterizing classes of tremor. Tremor Classification Criteria

Essential Essential Parkinsonian Dystonic Tremor (ET) Tremor Plus

Bradykinesia and Bilateral tremor of rigidity Tremor in a body part the upper limbs Same clinical affected by dystonia with or without features of ET Unilateral or head tremor or asymmetric Symptoms reduced by tremor of other resting tremor geste antagoniste locations (hands may (sensory tricks) Additional “soft” exhibit pill rolling Task specificity neurological signs tremor) Duration of at (e.g. mild memory Idiopathic, familial, or least 3 years impairment, Rest tremor sporadic impaired tandem diminishes with gait, subtle body Dystonia + tremor in Absence of initiation of different body parts = dystonia, ataxia, posturing similar to muscle dystonia) tremor associated with or parkinsonism contraction dystonia Vocal Tremor (VT)

• Neurological voice disorder • Involuntary rhythmic modulation of Raw audio – PITCH (fo) – LOUDNESS (SPL) SPL • Can be a primary fo symptom, or associated with: – Essential Tremor – Dystonia (Brown & Simonson, 1963; Perez, Ramig, & Smith, 1996; Woodson, 2008; – Parkinson Disease Woolraich, Marchis-Crisan, Redding, Khella, Mirza, 2010) Vocal Tremor (VT)

● General characteristics ● Best perceived during sustained task (Brown & Simonson, 1963; Lederle, Barkmeier-Kraemer, & Finnegan, 2012) ● Modulation of pitch and loudness can be further characterized(Gamboa et al, 1998; Dromey, Warrick, & Irish, 2002) ● RATE (3-12 Hz) ● MAGNITUDE (20-30%) ● Significantly slower speaking rate than normal speakers (3 vs 5 syllables/s) (Lundy, Roy, Xue, Casiano, & Jassir, 2004) ● May improve (lessen) when drinking alcohol, depending on etiology (Sulica and Louis, 2010) ● Voice stoppages/breathy breaks are rhythmic and associated with structural oscillations (Ludlow et al, 2018) CONCEPTUAL MODEL OF VOCAL TREMOR

The acoustic consequence of tremor affecting structures within the speech apparatus resulting in an involuntary rhythmic modulation of the voice

Figure taken from: Tortora, G.J. & Grabowski, S.R. (2003). The Respiratory System. In: Principles of Anatomy and Physiology Volume 4, The Maintenance and Continuity of the Human Body , 10th Edition (page 709). HOW DO WE CONCEPTUALIZE VOCAL TREMOR PHYSIOLOGY?

1. Respiratory System Oscillation – Subglottal pressure modulation – Ho: SPL modulation

(Simulations provided by Brad Story, University of Arizona) HOW DO WE CONCEPTUALIZE VOCAL TREMOR PHYSIOLOGY?

1. Oscillation – fo modulation (vocal fold length changes) – Ho: fo modulation – Glottal width modulation – Ho: SPL modulation (fo modeled as constant)

(Simulations provided by Brad Story, University of Arizona) HOW DO WE CONCEPTUALIZE VOCAL TREMOR PHYSIOLOGY?

4. Vocal Tract – Pharyngeal diameter and length modulation – Ho: Formant modulation • F1 and F2 modulation associated with SPL modulations

(Simulations provided by Brad Story, University of Arizona) VT Classification Criteria VT Classification Criteria

Essential Dystonic Parkinsonian Voice Tremor Tremor Tremor

Idiopathic action Tremor predominantly tremor affecting the evident in the larynx Tremor mostly voice as part of ET that is task specific associated with vertical (included isolated (i.e. occurs during laryngeal movement in vocal tremor) speech) those with idiopathic Parkinson’s disease (PD) Affects muscles of the larynx, pharynx, Tremor in the larynx palate, other associated with articulators, and laryngeal dystonia (LD) respiratory musculature Geste antagoniste (Sensory Tricks) lessen Tremor is not task the tremor (e.g. specific (occurs during placement of phonation and nasoendoscope) respiration) What do we need to classify VT?

• Medical History: – Age of onset of tremor (limbs, head, VT) – Onset associated with specific drugs or exposure to toxins – Condition(s) that improve VT (ETOH, sensory tricks) – Progression of tremor symptoms over time – Family history for VT or other forms of tremor – Signs of systemic illness – Diagnosed, or undiagnosed neurological signs – Signs of mild memory impairment, impaired tandem gait, or subtle body posturing (dystonia) Inter- or Multi-Disciplinary Team Evaluation

• Speech-language pathologist (SLP) – voice/speech patterns and function • Otolaryngologist (preferably a laryngologist) – Upper airway pathology • Neurologist (movement disorders specialist) – Assessment and classification of movement disorder • All team members contribute toward patient education/counseling and the need for additional consultation Evaluation of Neurogenic Voice Disorders

• Case history • Speech Motor Assessment – Cranial Nerve/Oral Mechanism Assessment – Speech Assessment • Diadochokinetic rate and integrity • Functional speech • Intelligibility and communication efficiency at word/sentence level • Auditory perceptual features with systematic speech assessment • Nasoendoscopic examination • Acoustic Analysis – primarily useful for vocal tremor detection and measurement

See: https://www.asha.org/PRPSpecificTopic.aspx?folderid=8589942600§ion=Assessment Clinical Features of VT

• Body Distribution – All structures with tremor – Symmetry (Right vs Left) • Activation condition – Quiet breathing (posturing) – Task specificity (only speech) – All tasks (respiration and speech tasks) • Frequency – Estimated rate of body part oscillation – Measured acoustic rate/extent Cranial Nerve/Tremor Assessment

Body Distribution Tremor Condition (Task) Symmetry Auditory-Perceptual Evaluation

• Systematic speech testing – Sustained phonation of vowels /a/ and /i/ across pitch/loudness levels – High pitch speech production tasks – Shouting of phrases (e.g. “Wait for me!”) – Counting from 60-70 (voiceless phonemes) and 80-90 (Voiced phonemes) – Imitation vs reading of sentences with voice-loaded and voiceless-loaded sentences (assess for laryngeal dystonia) Auditory-Perceptual Evaluation

ADductor Sentences ABductor Sentences 1) Tom wants to be in the army. 1. He is hiding behind the house. 2) We eat eels every day. 2. Patty helped Kathy carve the turkey. 3) He was angry about it all year. 3. Harry is happy because he has a new 4) I hurt my arm on the iron bar. horse. 4. During babyhood he had only half a 5) Are the olives large? head of hair. 6) John argued ardently about 5. Who says a mahogany highboy isn’t honesty. heavy? 7) We mow our lawn all year. 6. Boys were singing songs outside of our 8) Jane got an apple for Ollie. house. 9) A dog dug a new bone. 7. The puppy bit the tape. 10) Everyone wants to be in the 8. See, there’s a horse across the street. army. 9. Sally fell asleep in the soft chair. 10. The policy was suggested in an essay on peace. (Taken from: Ludlow et al, 2008: Location of frequent voice breaks are underlined) Comparison of two cases

Sustained Phonation Connected Speech

Case 1

Case 2

What is your perception of vocal tremor severity for each during sustained phonation? Connected speech? Differential Percepts

LDAD LDAB VT

Strained-strangled Breathy voice Rhythmic modulation of pitch quality or voice breaks/upward pitch and loudness during stoppages with voiced breaks with voiceless sustained phonation phonemes phonemes

Normal whispering, Voice stoppages or breathy Normal whispering, emotional speech, breaks are rhythmic or not emotional speech, vegetative voicing, and clearly phoneme specific vegetative voicing shouting

Tremor may be observable in externally visible speech >55% report sensory >55% report sensory tricks that temporarily improve structures during the clinical tricks that temporarily cranial nerve exam improve symptoms symptoms

Classification of VT type (e.g. essential vs dystonic) requires systematic comparison of clinical features Case Examples

LDAD LDAB VT LDAD +VT Nasoendoscopic Examination • No/minimal topical anesthesia should be used • Repeat speech examination tasks Assess – Note differences in speech disorder severity (nasoendoscopy as sensory trick) – Evaluate laryngeal function during vegetative activities – Respiration, cough, throat clear, and whistling – Observe presence, location and context of tremor • Assess velopharynx, pharynx, tongue, and larynx • Speech tasks of sustained phonation and connected speech • Record at least 4 cycles of respiration • Note body distribution and symmetry (bilateral/unilateral) • Note changes in VT severity by pitch and loudness to infer laryngeal muscle involvement (e.g. high pitch = CT; low pitch = TA, etc.) Case Example – Essential Tremor Acoustic Features of Case Example • Isolated VT (IVT) and essential tremor VT exhibited different demographics and clinical characteristics – IVT had an older age of onset, predominantly females, without spread to limbs – VT in those with Essential tremor equally affected males/females and frequently spread to affect the voice • Systematic testing for task specificity to distinguish VT and LD was not common : Diagnostic Tool & Treatment

• Diagnostically used to offload excessive throat muscle tension to: – Determine the diagnosis of LD versus severe (MTD) • Therapeutically used to: – Reduce excessive muscle tension that may undermine medical treatment outcomes – Teach communication strategies to address difficult speaking situations Treatment Options for Vocal Tremor

• Pharmaceutical – Systemic • Propranolol, primidone, octanoic acid, sodium oxybate – Local • Botox® to laryngeal muscles • Surgical – Deep Brain Stimulation (DBS) – Thalamic ablative I’ve always wanted • Voice therapy to be a mover and a shaker! (Adler et al, 2004; Bové et al, 2006; Ludlow, 1995; Moringlane et al, 2004; Sataloff et al, 2002; Sulica & Louis, 2010; Warrick et al, 2000; Barkmeier-Kraemer et al, 2011; Simonyan et al, 2013; Justicz et al, 2016; Nida et al, 2016; Erickson-DiRenzo et al, 2020; Lowell et al, 2021) Vocal Tremor Speech Treatment

• Vocal tremor is action-induced – Offloading excessive upper airway muscle contraction may reduce tremor amplitude • Voice duration determines vocal tremor perception – Voicing duration < 500 ms results in mild to no perception of vocal tremor • The contribution of specific structures can influence strategies – Altered Pitch/loudness intonation patterns may reduce vocal tremor Findings that Impact Treatment

• Tremor Characteristics – Important to compare sustained vs connected speech – Acoustic measures can be diagnostic – Laryngeal imaging confirms involved structures • Severity of Vocal Tremor – Compare between speech contexts – Ability to volitionally modify voicing duration

1. Lederle, A., Barkmeier-Kraemer, J., & Finnegan, E. (2012). Perception of vocal tremor during sustained phonation compared to sentence context. Journal of Voice, Sept;26(5):668.e1-9. 2. Twohig, A. & Finnegan, I. (2008). The effect of vowel duration on tremor severity for patients with vocal tremor. Honor’s Thesis, University of Iowa, Iowa City, IA. Vocal Tremor Severity With Manipulation of Voicing Duration

• Legato vs Staccato – Sample 1: – Sample 2

Twohig, A. & Finnegan, I. (2008). The effect of vowel duration on tremor severity for patients with vocal tremor. Honor’s Thesis, University of Iowa, Iowa City, IA. WHAT WORKS? • Target population = Mild-moderate vocal tremor • Critical therapy program elements include: – Respiratory-phonatory coordination – Shortened voicing duration • Secondary therapy program elements include: – Insertion of pauses or phrase breaks – Increased breathiness – Modification of intonation patterns • Typical therapy dosage – 6-8 treatment sessions: 1 session/week for 50-60 minutes – Daily home practice (10-15 minutes twice daily) • Treatment outcome variables – Sustained phonation acoustic measures (fo, SPL, F1, F2) – % detection of vocal tremor within connected speech – Patient self-report questionnaires Behavioral Treatment Considerations…

• Severity of tremor, particularly over time • Structures affected by tremor • Individual speaking patterns that worsen or lessen the perception of tremor • Motivation to pursue behavioral intervention – Strategies may not automatize • Ability to attend treatment sessions consistently • Adaptation with disease progression • Consider as a supplement to Botox® IN SUMMARY

1. The clinical features of vocal tremor are poorly characterized but require systematic testing 2. Assessment of clinical features using updated tremor classification criteria combined with recommendations by the AAO-HNS: – Provided insights regarding tremor affecting the voice, and – differential diagnosis between dystonia and other neurological syndromes 3. Speech treatment may benefit those with VT REFERENCES

1. Adler CH, Edwards BW, Bansberg SF. Female predominance in spasmodic dysphonia. J Neurol Neurosurg Psychiatry 1997;63:688. 2. Albanese A, Bhatia K, Bressman SB, DeLong MR, Fahn S, Fung, VSC, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK. Phenomenology and classification of dystonia: A consensus update. Movement Disorders, 2013, 28(7): 863-873. 3. Aronson, AE, Hartman, DE. Adductor spastic dysphonia as a sign of essential (voice) tremor. Journal of Speech and Hearing Disorders, 1981;46:52-58. 4. Bhatia KP, Bain P, Bajaj N, Elble RJ, Hallett M, Louis ED, Raethjen J, Stamelou M, Testa CM, Deuschl G. Consensus statement on the classification of . From the task force on tremor of the international Parkinson and Movement Disorder Society. Movement Disorders, 2018, 33(1): 75-87. 5. Bloch CS, Hirano M, Gould WJ. Symptom improvement of spastic dysphonia in response to phonatory tasks. Ann Otol Rhinol Laryngol 1985;94:51– 4. 6. Brin MF, Blitzer A, Stewart C. Laryngeal dystonia (spasmodic dysphonia): observations of 901 patients and treatment with . Adv Neurol 1995;78:237–252. 7. Brown, J. R., & Simonson, J. Organic voice tremor: A tremor of phonation. Neurology, 1963 ;13 :520-525. 8. De Lima Xavier L, Simonyan K. The extrinsic risk and its association with neural alterations in spasmodic dysphonia. Parkinsonism Relat Disord, 2019, May 24. pii: S1353-8020(19)30255-X. doi: 10.1016/j.parkreldis.2019.05.034. [Epub ahead of print]. 9. Dromey, C., Warrick, P., & Irish, J. The influence of pitch and loudness changes on the acoustics of vocal tremor. J Speech Language Hear Res, 2002;45:879-890. 10. Edgar JD, Sapienza CM, Bidus K, Ludlow CL. Acoustic measures of symptoms in abductor spasmodic dysphonia. J Voice 2001;15:362–72. 11. Erickson ML (2003). Effects of voicing and syntactic complexity on sign expression in adductor spasmodic dysphonia. Am J Speech Lang Pathol 2003;12:416–424. 12. Erickson-DiRenzo E, Kuijper FM, Barbosa DAN, Lim EA, Lin PT, Lising MA, Huang Y, Sung CK, Halpern CH. Multiparametric laryngeal assessment of the effect of thalamic deep brain stimulation on essential vocal tremor. Parkinsonism Relat Disord. 2020 Dec;81:106-112. doi: 10.1016/j.parkreldis.2020.10.026. Epub 2020 Oct 13. PMID: 33120071. 13. Gamboa, J., Jimenez-Jimenez, F. J., Nieto, A., Cobeta, I., Vegas, A., Orti-Pareja, M., . . . Garcia-Albea, E. Acoustic voice analysis in patients with essential tremor. Journal of Voice, 1998;12(4):444-452. REFERENCES

14. Hintze JM, Ludlow CL, Bansberg SF. Spasmodic dysphonia: A Review. Part 1: Pathogenic Factors, Otolaryngology-Head and Neck Surgery, 2017, 157(4): 551-557. 15. Izdebski K, Dedo HH, Boles L. Spastic dysphonia: a patient profile of 200 cases. Am J Otolaryngol 1984;5:7–14. 16. Konkiewitz, E Castelon; Trender-Gerhard, I.; Kamm, C., et al. Service-based survey of dystonia in Munich. Neuroepidemiology 2002;21:202–6. [PubMed: 12065883] 17. Koufman JA, Blalock PD. Functional voice disorders. Otolaryngol Clin North Am 1991;Oct;24(5):1059-73. Lederle, A., Barkmeier- Kraemer, J., & Finnegan, E. Perception of vocal tremor during sustained phonation compared with sentence context. Journal of Voice, 2012, 26 (5):668.e1-9. doi: 10.1016/j.jvoice.2011.11.001. Epub 2012 Apr 21. 18. Leonard R, Kendall K. Differentiation of spasmodic and psychogenic dysphonias with phonoscopic evaluation. Laryngoscope 1999; 109:295–300. 19. Lorch MP, Whurr R. Tracing spasmodic dysphonia: The source of Ludwig Traube’s priority. Annals of Otology, Rhinology & Laryngology, 2016, 125(8): 672-676. 20. Lorch MP, Whurr R. Morell Mackenzie’s contribution to the description of spasmodic dysphonia. Annals of Otology, Rhinology & Laryngology, 2016, 125(12): 976-981. 21. Lowell SY, Kelley RT, Dischinat N, Monahan M, Hosbach-Cannon CJ, Colton RH, Mihaila D. Clinical Features of Essential Voice Tremor and Associations with Tremor Severity and Response to Octanoic Acid Treatment. Laryngoscope. 2021 Apr 17. doi: 10.1002/lary.29558. Epub ahead of print. PMID: 33864634. 22. Ludlow CL. Management of the spasmodic dysphonias. In: Rubin JS, Sataloff RT, Korovin G, Gould WJ, editors. Diagnosis and treatment of voice disorders. New York, USA: Igaku-Shoin; 1995. pp. 436–454. 23. Ludlow CL, Adler CH, Berke GS, Bielamowicz SA, Blitzer A, Bressman SB, Hallett M, Jinnah HA, Juergens U, Martin SB, Perlmutter JS, Sapienza C, Singleton A, Tanner CM, Woodson GE. Research priorities in spasmodic dysphonia. Otolaryngology – Head and Neck Surgery, 2008;139:495-505. 24. Ludlow CL, Bassich CJ, Connor NP, Coulter, DC. Phonatory characteristics of vocal fold tremor. J Phonetics 1986;14:509 –15. 25. Lundy, D. S., Roy, S., Xue, J. W., Casiano, R. R., & Jassir, D. Spastic/spasmodic vs. tremulous vocal quality motor speech profile analysis. Journal of Voice, 2004;18(1):146–152. 23. Morrison MD, Rammage LA, Belisle GM, Pullan CB, Nichol H. Muscular tension dysphonia. J Otolaryngol 1983;12:302– 6. REFERENCES

24. Nutt JG, Muenter MD, Aronson A, Kurland LT, Melton LJ 3rd. Epidemiology of focal and generalized dystonia in Rochester, Minnesota. Mov Disord 1988;3:188 –194. 25. Parnes SM, Lavorato AS, Myers EN. Study of spastic dysphonia using videofiberoptic . Ann Otol Rhinol Laryngol 1978;87:322–326. 26. Patel, Liu, Galatsanos & Bless, 2011, Differential Vibratory Characteristics of Adductor Spasmodic Dysphonia and Muscle Tension Dysphonia on High-Speed Digital Imaging, Annals of ORL, 120(1): 21-32. 27. Perez, K.S., Ramig, L.O., Smith, M.E. The Parkinson larynx: tremor and videostroboscopic findings. Journal of Voice, 1996;Dec;10(4): 354-61. 28. Rodriquez AA, Ford CN, Bless DM, Harmon RL (1994) Electromyographic assessment of spasmodic dysphonia patients prior to Botulinum toxin injection. Electromyogr Clin Neurophysiol 34:403– 407. 29. Rontal M, Rontal E, Rolnick M, Merson R, Silverman B, Truong DD. A method for the treatment of abductor spasmodic dysphonia with botulinum toxin injections: a preliminary report. Laryngoscope 1991;101:911–914. 30. Roy N, Bless DM, Heisey D, Ford, CN. Manual circumlaryngeal therapy for functional dysphonia: an evaluation of short- and long- term treatment outcomes. J Voice 1997;11:321–31. 31. Roy N, Gouse M, Mauszycki SC, et al. Task specificity in adductor spasmodic dysphonia versus muscle tension dysphonia. Laryngoscope 2005;115:311–316. 32. Roy N, Mauszycki SC, Merrill RM, et al. Toward improved differential diagnosis of adductor spasmodic dysphonia and muscle tension dysphonia. Folia Phoniatr Logop 2007;59:83–90. 33. Roy N, Whitchurch M, Merrill RM, et al. Differential diagnosis of adductor spasmodic dysphonia and muscle tension dysphonia using phonatory break analysis. Laryngoscope 2008; 118:2245–2253. 34. Sapienza CM, Walton S, Murry T. Adductor spasmodic dysphonia and muscular tension dysphonia: acoustic analysis of sustained phonation and reading. J Voice 2000;14:502–20. 35. Schweinfurth JM, Billante M, Courey MS. Risk factors and demographics in patients with spasmodic dysphonia. Laryngoscope 2002;112:220 –3. 36. Simonyan K, Barkmeier-Kraemer J, Blitzer A, Hallett M, Houde JF, Jacobson Kimberley T, Ozelius LJ, Pitman MJ, Mark Richardson R, Sharma N, Tanner K; NIH/NIDCD Workshop on Research Priorities in Spasmodic Dysphonia/Laryngeal Dystonia. Laryngeal Dystonia: Multidisciplinary perspectives on terminology, pathophysiology, and research priorities. Neurology. 2021 Apr 15:10.1212/WNL.0000000000011922. doi: 10.1212/WNL.0000000000011922. Epub ahead of print. PMID: 33858994. REFERENCES

37. Simonyan K, Frucht SJ. Long-term Effect of Sodium Oxybate (Xyrem®) in Spasmodic Dysphonia with Vocal Tremor. Tremor Other Hyperkinet Mov (N Y). 2013 Dec 9;3:tre-03-206-4731-1. doi: 10.7916/D8CJ8C5S. PMID: 24386608; PMCID: PMC3863985. 36. Stager SV, Bielamowicz SA, Regnell JR, Gupta A, Barkmeier JM. Supraglottic activity: evidence of vocal hyperfunction or laryngeal articulation? J Speech Lang Hear Res 2000;Feb;43(1):229-38. 37. Tanner K, Roy N, Merrill RM, Sauder C, Houtz DR, Smith ME. Spasmodic dysphonia: onset, course, socioemotional effects, and treatment response. Ann Otol Rhinol Laryngol. 2011 Jul;120(7):465-73. doi: 10.1177/000348941112000708. PMID: 21859056. 38. Tanner K, Roy N, Merrill RM, Sauder C, Houtz DR, Smith ME. Case-control study of risk factors for spasmodic dysphonia: A comparison with other voice disorders. Laryngoscope 2012;122:1082-1092. 39. White LJ, Klein AM, Hapner ER, Delgaudio JM, Hanfelt JJ, Hyder AJ, Johns MM. Coprevalence of tremor with spasmodic dysphonia: A case-control study. Laryngoscope 2011;1752-1755. 39. Woodson, G. Management of neurologic disorders of the larynx. Ann Otol Rhinol Laryngol, 2008;117:317-326. 40. Wolraich, D., Marchis-Crisan, C.V., Redding, N., Khella, S.L., Mirza, N. Laryngeal tremor: Co-occurrence with other movement disorders. , 2010;72:291-294. 41. Xiao J, Zhao Y, Bastian RW, Perlmutter JS, Racette BA, Tabbal SD, Karimi M, Paniello RC, Wszolek ZK, Uitti RJ, Van Gerpen JA, Simon DK, Tarsy D, Hedera P, Truong DD, Frei KP, Dev Batish S, Blitzer A, Pfeiffer RF, Gong S, LeDoux MS. Novel THAP1 sequence variants in primary dystonia. Neurology 2010;74: 229–238.