BOTOX THERAPY IN THE LARYNGOPHARYNX

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BOTOX THERAPY IN THE LARYNGOPHARYNX

• Sam J. Cunningham, MD, PhD
• David Teller, MD
• University of Texas Medical Branch
• Galveston, Texas
• October 2004

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Overview

• Review of Botox
• Overview of uses in the laryngopharynx
• Spasmodic dysphonia
• Types
• Anatomy
• Botox techniques

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Clostridium botulinum

• Spore forming obligate anaerobic bacillus
• Gram (young cultures)
• Produces a potent neuroexotoxin
• Causes the disease botulism

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Botox Species

• Divided into 4 groups (I-IV)
• Produce 7 different botulinum neurotoxin
  serotypes
• Group I A, B, F
• Group II B, E, F
• Group III C, D
• Group IV G

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Pharmacology

• 7 neurotoxins, serotypes A-G
• Antigenically distinct
• Similar molecular weights (150 kDa)
• Dichain molecule (heavy and light)-active
  molecule
• 3 functional domains
• Binding domain (C terminus of H chain)
• Translocation domain (N terminus of H chain)
• Catalytic domain (C terminus of L chain) Zn
  metalloprotease

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Pharmacology

• 3 steps in toxin-mediated paralysis
• Step1 Binding
• BTX-A binds irreversibly to motor
  endplates
• Step 2 Internalization
• Internalized by endocytosis
• Step 3 Inhibition of neurotransmitter release

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Pharmacology

• After internalization Cleaves proteins required
  for release of Ach vesicles (fusion or docking
  proteins)
• SNARE proteins
• N-ethylmaleimide-sensitive factor attachment
  protein receptor
• Each serotype binds to a specific residue of one
  of the docking proteins

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• SNARE proteins (i.e. fusion or docking proteins
• Synaptobrevin (B,D,E,G)
• SNAP-25 (A,C,E)
• Syntaxin (C)

• Prevents release of Ach
• Irreversible
• Results in flaccid paralysis

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Pharmacology

• Paralysis is seen 24-48 hours after injection
• presynaptic vesicles are depleted
• Recovery
• Initially new axons sprout 28 days
• Return of synaptic function of the initial NMJ
  91 days
• Muscle function usually present by 3 to 4 months

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Pharmacology

• Duration of neurotransmitter inhibition varies
  among serotypes
• Based on the cleavage of different SNARE proteins
  
• Different SNARE proteins, different duration of
  action among serotypes
• AgtC1gtBgtFgtE

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Pharmacology

• Potency
• Determined through in vivo mouse assays
• 1 U of BTX-A median intraperitoneal lethal dose
  (LD50) in female Swiss-Webster mice
• Estimated human LD50 2500-3500 Units

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Botox Uses in the Laryngopharynx

• Stuttering
• Vocal tics
• Puberophonia
• Ventricular dysphonia/Dysphonia plica
  ventricularis
• Dysphagia
• TEP speech failure
• Prevention of posterior glottic stenosis and
  recurrent vocal fold granuloma
• Arytenoid Rebalancing
• Bilateral vocal fold paralysis
• SPASMOTIC DYSPHONIA

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Stuttering

• Affects children and adults
• Patients often stigmatized, teased, etc
• Affects 1 of adult population
• Involuntary break in vocal fluency
• Larynx, pharynx, lips, oral cavity
• Decrease laryngeal contribution by injecting the
  thyroarytenoid muscles
• Return of symptoms in 12 weeks

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Vocal Tics

• Tourettes syndrome
• Repetitive dyskinetic movements of eyes, facial
  muscles, neck, oral cavity
• Dyskinetic movements of larynx-leads to grunts,
  abrupt breaks in fluency, and complex formations
  like screams, loud talking, repetitive word or
  vowel sounds, copralalia
• Botox injections into thyroarytenoid muscles have
  shown clinical improvements

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Puberophonia

• AKA mutational dysphonia
• Men and adolescent boys
• Higher fundamental frequency of prepubescent
  years
• Speech and behavioral therapy
• Botox as adjunct into cricothyroid muscles
• Enables larynx to relax and allow for lowering of
  pitch

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Ventricular dysphonia/Dysphonia plica
ventricularis

• Hyperfunctioning of supraglottic larynx
• Over adduction of false vocal folds
• Propagation of fundamental frequency from FVCs
• Gravelly, wet, hoarse quality voice-prone to
  vocal fatigue
• Compensatory response after injury, cysts, sulci
  allowing air escape
• Botox injections into the false vocal folds
• Aryepiglottic muscle

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Dysphagia

• Cricopharyngeal dysfunction and dyscoordination
• Botox into cricopharyngeus
• Identify patients that would benefit from CPM

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TEP speech failure

• Post laryngectomy if no CPM
• Patients with good TEP speech initially, then fail

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Vocal fold granuloma and prevention of posterior
glottic stenosis

• Following repair of posterior glottis clefting
  (interarytenoid)
• Recurrent granulation/scarring
• Botox into the thyroarytenoid muscles to decrease
  the strength of vocal fold closure and allow more
  lateral position at rest
• Decreases strength of vocal fold closure to help
  in treatment of vocal fold granuloma (less local
  trauma)

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Arytenoid rebalancing

• Arytenoid dyslocation following traumatic
  intubation or blunt trauma to anterior neck.
• Hoarseness/breathiness after surgery
• Immobile vocal cord
• EMG analysis and operative endoscopy
• Endoscopic manipulation of arytenoid back into
  native position
• Botox injected into interarytenoid muscle,
  ipsilateral thyroarytenoid muscle, and lateral
  cricothyroid muscle
• Weakens ipsilateral adductory muscles, allowing
  ipsilateral abductor to provide traction on the
  arytenoid allowing a more physiologic position

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Bilateral vocal cord paralysis

• Botox injected into the thyroarytenoid and
  interarytenoid muscles
• Weakens the adductory muscles, allowing increased
  patency of the airway at rest and with activity
• Rebalance position of the paralyzed cords to a
  more abducted position

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Spasmodic Dysphonia

• Usual onset in mid 30s
• More common in women (63)
• Two types ADductor and ABductor
• Dx based on careful history and examination of
  the glottis during a variety of laryngeal tasks

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Adductor Dysphonia

• Most common-80
• Inappropriate glottal closure
• Produces harshness, strain, and strangled breaks
  in connected speech

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Adductor Spasmodic Dysphonia

• Most common type
• Hyperactivity of the thyroarytenoid m. (TA)
• Inappropriate closing or tightness of the glottis
• Strained voice

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Abductor Dysphonia

• Less common
• Inappropriate glottal opening
• Produces hypophonia and breathy breaks

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Abductor Spasmodic Dysphonia
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Spasmodic Dysphonia

• Treatment alternatives to Botox
• Surgical denervation crush, neurolysis
• Speech therapy (adjunct)
• ? Psychological therapy
• American Academy of Otolaryngology-Head and Neck
  Surgery endorses Botox as primary therapy for
  this disorder. (Policy Statement Botulinum
  Toxin. Reaffirmed March 1, 1999)

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Injection Strategy

• Adductor spasmodic dysphonia EMG-guided
  transcutaneous injections of the thyroarytenoid
  muscle, using equal amounts of Botox (1-1.25U
  initially)
• Abductor spasmotic dysphonia EMG-guided
  transcutaneous injection of one posterior
  crycoarytenoid muscle with Botox (3.75U
  initially)

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Adductor spasmodic dysphonia Injection Technique

• Reclined position with neck extended
• Local anesthesia unnecessary (hinder)
• Bend needle 30-450 (esp in women)
• Insert needle through skin just off midline at
  level of cricothyroid membrane
• Characteristic buzz when in airway
• Advance superiorly and laterally
• Patient asked to phonate for EMG confirmation
• Botox injected

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Thyroarytenoid injection
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Injection for Spasmodic Dysphonia

• Supine with neck extended
• /-Local anesthetic for TA injection
• EMG guidance

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Inj. for adductor spasmodic dys.
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TA injection with Botox
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Abductor spasmodic dysphonia Injection technique

• PCA may be reached in two ways
• Retrocricoid (lateral) approach
• transcricoid (anterior) approach

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Abductor spasmodic dysphonia Lateral approach

• Thumb placed on posterior aspect of thyroid
  cartilage and entire larynx is rotated to expose
  the posterior aspect
• Insert needle along the lower half of the
  posterior edge of the thyroid cartilage,
  traversing the inferior constrictor, and advance
  until the cricoid is encountered.
• Pull needle back slightly and ask the patient to
  sniff
• EMG confirmation and Botox injected

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Abductor spasmodic dysphonia Lateral approach
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PCA injection with Botox (lateral approach)
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Abductor spasmodic dysphonia Transcricoid
approach

• Insert needle through the cricothyroid membrane
  in the midline
• Characteristic buzz in lumen
• Pass through the posterior lamina of the cricoid
  cartilage to either side of midline
• Topical lidocaine to prevent coughing (does not
  hinder)
• First electrical signal encountered is PCA
• Placement confirmed by sniffing and Botox
  injected
• Better in younger patients (cartilage is not
  calcified)

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Abductor spasmodic dysphonia Transcricoid
approach
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PCA injection with Botox (transcricoid approach)
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Conclusions

• Botulinum toxin therapy is an extremely useful
  and versatile tool in the laryngologists
  armamentarium. By chemically denervating the
  various laryngeal muscles, it is possible to
  effectively diagnose and treat a number of
  disorders of the laryngopharynx.

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References

• Blitzer, A et al Botulinum toxin management of
  spasmodic dysphonia (laryngeal dystonia) A
  12-year experience in more than 900 patients.
  Laryngoscope 1081435-14441, 1998.
• Hogikyan, ND et al Longitudinal effects of
  botulinum toxin injections on voice-related
  quality of life for patients with adductory
  spasmodic dysphonia. J Voice 15576-586, 2001.
• Benninger MS et al Outcomes of botulinum toxin
  treatment for patients with spasmodic dysphonia.
  Arch Otolaryngology Head and Neck Surgery
  1271083-1085, 2001.
• Maloney, AP et al A comparison of the efficacy
  of unilateral vs bilateral botulinum toxin
  injection in the treatment of adductor spasmodic
  dysphonia. J Otolaryngology 23160-164, 1994
• Blitzer, A Botulinum Toxin Therapy. Operative
  Techniques in Otolaryngolgy Head and Neck
  Surgery. 152, 2004.
• Blitzer, A et al Botulinum toxin Basic science
  and clincal uses in otolaryngolgy. Laryngoscope.
  111218-226, 2000.
• Jankovic, J Botulinum toxin in the treatment of
  tics. Therapy with botulinum toxin. New York,
  Dekker, 1994, pp503-509.
• Rosen, CA et al Botox for hyperadduction of the
  false vocal folds a case report. J. Voice
  13234-239, 1999.
• Woodson, GE et al Botulinum toxin in the
  treatment of recalcitrant mutational dysphonia.
  J Voice 8347-351, 1994.

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References cont.

• Nathon, CO et al Botulinum toxin Adjunctive
  treatment for posterior glottic synechiae.
  Laryngoscope 109855-857, 1999.
• Orloff, LA et al Vocal fold granuloma
  Successful treatmetn with botulinu toxin.
  Otolaryngology-Head and Neck Surgery 121410-413,
  1999.
• Muller, C Botox. Oral presentation. UTMB.
  2003.
• Ashan, SF et al Botulinum toxin injection of the
  crycopharyngeus muscle for the treatment of
  dysphagia. Otolaryngology head and neck surgery
  122691-696, 2000.
• Netter, FH Human anatomy. Ciba.
• Rontal E et al Laryngeal rebalancing for the
  treatment of arytenoid dislocation. J voice.
  12383-388, 1998.