1. Spasmodic Dysphonia Evaluation and Management
UTMB Department of Otolaryngology
Olvia Revelo, MSIV
Faculty Advisor:Michael Underbrink, MD
Grand Rounds Presentation
March 10, 2009

2. Overview Introduction Anatomy of the larynx Etiology Diagnosis
Clinical features
Therapy
Pharmacologic
Surgical
Conclusion

3. Introduction Spasmodic dysphonia (SD)
Focal, adult-onset dystonia of laryngeal muscles
Intermittent phonatory breaks during speech secondary to spasms
Usually task specific - symptomatic when attempting voluntary speech
May be asymptomatic during reflexive phonation (coughing, laughing, crying, yawning)
Symptoms reduced/absent during singing or whisper

4. Associations May be associated with: Other focal dystonias
Blepharospasms, Torticollis, Writer’s Cramp
Underlying neurological
Parkinson’s, ALS
Environmental
Infection, trauma, meds
Psychogenic stimulus
Stress

5. Demographics Affects approximately 1:10,000 Americans
Female to male ratio 3:1 up to 8:1
Peak age of onset 35-45
Positive family history in 12% of affected pt’s

6. Types of Laryngeal Dystonias
Adductor – irregular hyperadduction of vocal folds with excessive glottic closure
Abductor – incomplete, irregular vocal fold approximation
Mixed – both elements are present

7. Anatomy: Laryngeal Cartilage
Netter

8. Anatomy: Laryngeal Cartilage
Netter

9. Anatomy: Laryngeal Muscles
Netter

10. Anatomy: Laryngeal Muscles
Netter

11. Anatomy: Laryngeal Motion
Abduction of vocal ligament
Netter

12. Anatomy: Laryngeal Motion
Adduction of vocal ligament
Netter

13. Anatomy: Laryngeal Motion
Tension of vocal ligament
Netter

15. Anatomy: Laryngeal Innervation
Netter

16. Etiology Currently unknown Historically psychogenic disorder
Traube 1871 “nervous hoarseness”
Current theory involves neurologic cause
Basal ganglia involved in other focal dystonias
Some patients have developed SD post head trauma

17. Diagnosis
Diagnosis is based on history and examination of the glottis during various laryngeal tasks.
Aronson defined “idiopathic spastic dysphonia”:
The voice signs of SD
Absence of VC lesions/paralysis
Normal peripheral speech mechanisms
Resistance of symptoms to voice therapy and psychotherapy

18. Clinical Features: Adductor Type
Most common ~85% of diagnosed cases
Choked, strained-strangled voice, with abrupt breaks in phonation in the middle of vowels
Breaks are due to hyper-adduction of the folds
Difficulty with “We eat eels every day” and “We mow our lawn all year”

19. Clinical features: Abductor Type
Rare ~15% of patients with SD
Breathy, effortful voice with abrupt breaks resulting in whispered elements of their speech.
Excessive and prolonged abduction during voiceless consonants (/h/,/s/,/f/,/p/,/t/,/k/)
Difficulty with “The puppy bit the tape” and “When he comes home we’ll feed him”

20. Mixed Type
Extremely rare, with symptoms of both adductor and abductor type
Diagnosis important for predicting treatment response

21. Diagnosis Electromyography Fiberoptic laryngoscopy Videostroboscopy
Aerodynamic testing
Vocal spectrographic analysis

22. Therapy Pharmacotherapy Voice Therapy Surgical Botox
Neuropharmacologic
Voice Therapy
Surgical
Recurrent laryngeal nerve section
Recurrent laryngeal nerve avulsion

23. Therapy Surgical - Experimental
Recurrent laryngeal nerve denervation and reinnervation
Type II thyroplasty
Posterior cricoarytenoid myoplasty with medialization thyroplasty

24. Botulinum Toxin Goldstandard treatment for SD
Prevents presynaptic release of acetylcholine (Ach) at neuromuscular junction.
Different serotypes of botulinum toxin exhibit specific proteolysis of proteins involved in transport and binding of Ach vesicles to presynaptic membrane.
Result in temporary paralysis

25. Botox mechanism of action
Release of acetylcholine at the neuromuscular junction is mediated by the assembly of a synaptic fusion complex that allows the membrane of the synaptic vesicle containing acetylcholine to fuse with the neuronal cell membrane. The synaptic fusion complex is a set of SNARE proteins, which include synaptobrevin, SNAP-25, and syntaxin. After membrane fusion, acetylcholine is released into the synaptic cleft and then bound by receptors on the muscle cell.
JAMA. 2001;285:

26. Botox mechanism of action
Botulinum toxin binds to the neuronal cell membrane at the nerve terminus and enters the neuron by endocytosis. The light chain of botulinum toxin cleaves specific sites on the SNARE proteins, preventing complete assembly of the synaptic fusion complex and thereby blocking acetylcholine release. Botulinum toxins types B, D, F, and G cleave synaptobrevin; types A, C, and E cleave SNAP-25; and type C cleaves syntaxin. Without acetylcholine release, the muscle is unable to contract.

27. Botulinum Toxin Effects and Side Effects:
Reduction in voice breaks reported by 48 hrs
Treatment lasts an average of 3-4 months before recurrence of symptoms
Most common side effect is breathiness
Other side effects include: dysphagia, prologued voice loss, aspiration, hoarseness, pain at injection site and stridor (with PCA injection)

28. Botulinum Toxin No absolute contraindications Used safely in children
Give antireflux medication to patients with reflux
3 – 5% of patients have developed resistance to the toxin
Resistant patients can sometimes be treated with other toxin serotypes

29. Botulinum Toxin Injection technique for adductor SD (AdSD)
Percutaneous injection guided by electromyographic (EMG) signals.
Needle inserted through thyrocricoid membrane and directed upward toward contralateral thyroarytenoid m.
Phonation and observation of interference pattern on EMG verifies position

30. Thyroarytenoid injection for adductor spasmodic dysphonia
Thyroarytenoid injection for adductor spasmodic dysphonia. Needle is advanced through the cricothyroid membrane.
Pitman MJ

31. Botulinum Toxin
Alternate injection techniques for AdSD All methods yield comparable results. Very patient and physician dependent.
Transoral laryngoscopic injections
The transoral approach involved indirect visualization of the VF via standard laryngoscopicprecedure. VF anesthetized through application of topical cocaine sol’n. BTX is then injected along the superior margin of the VF
Transnasal laryngoscopic injections
Transnasal technique uses a flexible nasolaryngoscope with a working channel that is equipped with a flexible catheter needle. Topical phenylephrine and lidocaine are sprayed transnasally, then the scope is introduced. Once in place, lidocainesol’n drip is applied to the surface of the VF via the working channel while the pt phonates to prevent airway penetration or aspiration. Then inject just lateral to the true VF (to avoid damage to VF mucosa)
Transcartilaginous “point touch” injections
Insertion of the needle through the surface of the thyroid cartilage halfway b/w thyroid notch and inferior edge. Following insertion the needle is passed through the cartilage and into TA muscle where BTX is injected

32. Botulinum Toxin Injection technique for abductor SD (AbSD)
Requires access to posterior cricoarytenoids
Larynx is rotated manually away from injection site. Needle passed posterior to the posterior edge of thyroid at cricoid level into the PCA.
Patient is asked to sniff to contract PCA and verify correct position

33. Posterior cricoarytenoid (PCA) injection for abductor spasmodic dysphonia. Needle is advanced through the inferior constrictor muscle to the PCA muscle.
Pitman MJ

34. Botulinum Toxin Blitzer et al. 1999
Reported their 12 yr experience with more than 900 patients with SD
90% of patients with AdSD and 66.7% with AbSD achieved a normal voice after injection
Injection after nerve section failure showed up to 81% improvement
Patients with combined abnormalities only had 30% improvement -Level of evidence (LOE): A

35. Botulinum Toxin Advantages Disadvantages Less invasive than surgery
No permanent damage to nerve or laryngeal structures
Temporary nature allows for dosage adjustments
Readily available
Disadvantages
Need for repeated injections
Unpredictable relationship between dosage and response
Resistance to treatment
Adverse side effects

36. Pre-Botox Treatment

37. Post-Botox Treatment

38. Pre-Botox Treatment

39. Post-Botox Treatment

40. Neuropharmacology
No controlled studies demonstrate effective symptom control
Beta blockers – propranolol
Anticholinergics – trihexyphenidylHCl (Artane)
Benzodiazepines – diazepam, alprazolam
Role has been to provide relief without any demonstrable symptom reduction

41. Voice Therapy No demonstrated effectiveness in treating SD May help:
Rule out psychogenic disorder
Provide support for those who do not benefit from Botox (mild symptoms)
Some patients use it in adjunct to Botox to prolong symptom free period
Traditional voice therapy approaches for ADSD employ techniques for avoiding overpressure. Breathy voice onsets, reduced speech force, using a head focus, and laryngeal manipulation are aimed at reducing laryngeal tension. Can also use relaxation and respiration training to help gain insight and control of laryngeal tension during speech.

42. Recurrent laryngeal nerve section
Dedo 1976
Case series of 34 patients that had RLN section
“All experienced symptom improvement”
No objective measurement of outcome -LOE:C
Dedo 1991
Retrospective review of 300 patients after RLN section
82% had little or no symptoms after 5-14 years
No prospective comparative data available -LOE:B
(add pics and make it 2 slides if necessary)
Dedo first recognized that ADSD could be surgically treated d/o.
His first publication was a case series in which he describes the outcomes of 34 pts who underwent RLN. They observed that RLN paralysis retract the involved VC from midline (in paramedian position) so the nml fails to reach as firmly as usual, causing a breathy but often phonatory soft voice. Tried lidocaine injections on one of his pts who was relieved of the spasms and agreed to indogoe RLN section for a more permanent relief. He then sectioned the RLN in 34 pts after they showed improvement after Xylocaine temporary paralysis showed significant improvement in vocal quality.
They treated pts w unilateral RLN section. Thinking that the Creation of unilateral VC paralysis could prevent hypperadduction and loss of speech fluency at the cost of the dysphonia associated with paralysis.
In his 1991 publication, which was a retrospective review of pre and post operative I recordings, of 300 pts who underwent RLN section. Pts answered questionaires regarding voice production and voice recordings analyzed by perceptual voice eval and acoustic analysis of voice spectra. 15% developed recurrence of mild to moderate spasticity 6-24mo after RLN section. – curable w laser cord thinning via DL. 82% had little or no voice spasticity 5-14yr after RLN section
Aronson and DeSanto
Since then, this approach has been abandoned by most laryngologists in favor of the reliability of BTX injections.

43. Recurrent laryngeal nerve section
Aronson and DeSanto 1983
Followed 33 patients for 3 years post RLN section
36% maintained improved voices
Of the 64% failed voices, 48% were worse than before surgery
Effectiveness of unilateral RLN section for severe ADSD decreases with time
Limitations: small sample study -LOE:C
(Pics from article – scan)
They concluded that the effectiveness of unilat RLN section for severe ADSD decreases with time and results in voice failure in a sizeable percentage of patients.
Return of sxs not due to reactivation of VC, but hyper adduction of normal VF alone or along with other m of supra glottis and extrinsic laryngeal m.
Since this study RLN section was widely abandoned for the simpler BTX injection method for temporary relief of SD sxs.

44. Recurrent laryngeal nerve avulsion
Netterville 1991
Retrospective review of 12 patients
No recurrence at 1.5 years LOE:C
Follow up report 1996
18 patients followed for 3-7 yrs post RLN avulsion
16/18 patients were without spasm
Most common side effect was breathy voice – Six underwent medialization laryngoplasty LOE:C

45. Therapy Surgical Experimental
Recurrent laryngeal nerve denervation and reinnervation
Type II thyroplasty
Posterior cricoarytenoidmyoplasty with medializationthyroplasty

46. Recurrent laryngeal nerve denervation and reinnervation
Berke and Blumin 2006
Retrospective study analyzing satisfaction surveys and perceptual evaluation of post operative voice
83 of 136 patients returned surveys with 91% satisfied with fluency of voice
46 patients provided voice recordings for perceptual evaluation: 26% had voice breaks, and 30% breathiness -LOE:B

47. Recurrent laryngeal nerve denervation and reinnervation
Limitations: high drop out rate (61%), small sample size, no long term prospective studies
Disadvantages
Technical difficulty
Recurrence of symptoms
Does not prevent unwanted reinnervations
Advantages
Permanent effect
Less breathiness due to maintenance of VF tone from ansa cervicalis innervation

48. Midline lateralization thyroplasty
Isshiki et al. 2001
Retrospective review of 6 SD patients
5/6 patients obtained near normal voices
Failure attributed to difficulty in lateralization and concurrent focal neck dystonia
Limitations: small samples, no long term prospective studies, no objective measures described -LOE:C

49. Atlas of Head & Neck Surgery—otolaryngology By Byron J. Bailey, Karen H. Calhoun, Norman

50. Modified Type II Thyroplasty
Midline lateralization thyroplasty (type 2 thyroplasty) after completion of the procedure. “A” type using a composite graft for the closure of a tiny perforation at or slightly above the anterior commissure. A muscle flap is used to cover the graft. G = A composite graft.
Isshiki: Laryngoscope, Volume 111(4).April

51. Modified Type II Thyroplasty
B” type without using a graft. (A) The incised edges are pulled apart to test the lateralization effect on voice. (B) The incised edges are separated at a desired distance (usually 3–4 mm) and fixed with silicone shims.
Isshiki: Laryngoscope, Volume 111(4).April

52. Midline lateralization thyroplasty
Chan 2004
Prospective case series with 13 subjects
Used method described by Isshiki
9/13 patients failed; 2 had their surgery reversed
Reason for failure unclear
Limitations: small sample, only used self-rating assessments and no objective measures LOE:C
Unclear why some pts deteriorate over time, especially when they had good early results p sx. Presume that with time the VF hyperadduction is able to overcome the initial lateralization created by the shims because the underlying neuropathology has not been resolved.
Continue to recommend BTX as gold standard.

53. Midline lateralization thyroplasty
Advantages:
Optimal glottal closure can be adjusted and readjusted
No damage of physiologic function
Reversible
Disadvantages:
Technically difficult
Shim displacement
Does not relieve cause of SD
Require careful patient selection
Lacks reproducibility
Limitations of a retrospective study

54. Posterior cricoarytenoid myoplasty with medialization thyroplasty
Shaw 2003
Case report of 3 patients with AbSD refractory to BTX treated with surgery and followed up to a year post surgery
All reported improved subjective symptoms and showed objective reduction in phonatory breaks
Limitations:
Small sample and no long term prospective outcomes -LOE:D

55. Posterior cricoarytenoid myoplasty with medialization thyroplasty
Shaw , Ann OtolRhynolLaryngol (2003) 112:

56. Summary Treatment Advantage Disadvantage Botulinum Toxin
Type A (Botox)
Current “gold standard”; Readily available; less invasive
Not permanent cure; risk of immunoresistance; “breathy” voice
Type B (Myobloc)
Alternative for resistant patients
Limited availability and use in SD
Voice Therapy
Inexpensive; No side effects; non-invasive; no contraindications; adjunct to BTX
Not effective alone; requires high patient compliance; takes time to learn
RLN Section / Avulsion
“permanent” treatment
Invasive; symptom recurrence
Laryngeal adductor denervation-reinnervation
“permanent” treatment; option for patients resistant to BTX
Invasive; limited availability and long term outcome data
Laryngeal framework approach
“permanent” treatment; does not target nerve function, reversible
PCA myoplasty with medializationthyroplasty
“permanent” treatment; does not target nerve function

57. Summary
SD is an idiopathic d/o of the larynx. The mainstay of treatment continues to be BTX injections into the laryngeal muscles. BTX txt is not perfect -- there is an onset time characterized by a breathy voice and dusphagia and an offset time characterized by a recurrence of sxs. Occasionally pts can develop antibodies and resistance. Some pts don’t like to receive multiple injections a year. Because of these shortcomings alternative, more permanent treatments have been sought. Surgery for ASDS was initially developed in the 1970s but has been abandoned because of poor long term results. A RLN denervation and reinervation and laryngoplastic techniques may hold promise for long term treatment. All current therapies for SD are directed toward the symptoms of the d/o. There is still work toward understanding the underlying cause so we can then possibly develop a cure to the disease.

58. References
Pearson EJ and Sapienzam CM. Historical approaches to the treatment of Adductor-Type Spasmodic Dysphonia: Review and tutorial. NeuroRehabilitation (2003) 18:
Sulica L. Contemporary management of spasmodic dysphonia. CurrOpinOtolaryngol Head Neck Surg (2004) 12:
Berke GS and Blumin JH. Spasmodic dysphonia: therapeutic options. CurrOpinOtolaryngol Head Neck Surg (2000) 8:
Grillone GA and Chan T. Laryngeal Dystonia. OtolaryngolClin N Am (2006) 39:87-100
Blitzer A, Brin MF, Stewart C. Botulinum toxin management of Spasmodic Dysphonia: 12-year experience in more than 900 patients. Laryngoscope (1998) 108(10):
Mehta RP et al. Long-term therapy for spasmodic dysphonia-acoustic and aerodynamic outcomes. Arch Otolaryngol Head Neck Surg (2001) 127:
Aronson AE and DeSanto LW. Adductor spastic dysphonia: three years after recurrent laryngeal nerve resection. Laryngoscope (1983) 93:1-8
Dedo HH and Behlau MS. Reccurent laryngeal nerve section for spastic dysphonia: 5 to 14 year preliminary results in the first 300 patients. Ann OtolRhinolLaryngol (1991) 100:
Dedo HH. Recurrent laryngeal nerve section for spastic dysphonia. Ann Otol (1976) 85:451459
Weed DT et al. Long term follow up of recurrent laryngeal nerve avulsion for the treatment of spastic dysphonia. Ann OtolRhinolLaryngol (1996) 105:

59. References
Netterville JL et al. Recurrent laryngeal nerve avulsion for traemtent of spasmodic dysphonia. Ann OtolRhinolLaryngol (1991) 100:10-14
Chhetri DK, Mendelsohn AH, Blumin JH, Berke GS. Long term follow up results of selective laryngeal adductor dennervation-reinnervation surgery for adductor spasmodic dysphonia. Laryngoscope ( 2006) 116:
Berke GS et al. Selective laryngeal adductor denervation-reinnervation: a new surgical treatment for adductor spasmodic dysphonia. Ann OtolRhinolLaryngol (1999) 108:
Isshiki N et al. Midline lateralization thyroplasty for adductor spasmodic dysphonia. Ann OtolRhinolLaryngol (2000) 109:
Isshiki N, Yamamoto I, Fukagai S Type 2 thyroplasty for spasmodic dysphonia fixation using a titanium bridge. ActaOtolaryngol (2004) 124:
Isshiki N et al. Thyroplasty for adductor spasmodic dysphonia: further experience. Laryngoscope (2001) 111:
Shaw GY, Sechtem PR, Rideout B. Posterior cricoarytenoidmyoplsty with medializationthyroplasty in the management of refractory abductor spasmodic dysphonia. Ann OtolRhynolLaryngol (2003) 112:
Simonyan K et al. Focal white matter changes in spasmodic dysphonia: a combined diffusion tensor imaging and neuropathological study. Brain (2008) 131:
Jurgens U. Neural pathways underlying vocal control. Neuroscience and Biobehavioral Reviews (2002) 26:

60. References
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Cummings
Shaefer SD. Neuropathology of spasmodic dysphonia. Laryngoscope (1983) 93:
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