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specifics, including dosage, injection location, and time between treatments. A management algorithm for EVT was proposed based on the observed phenomenology, treatment outcomes, and the 20 years of experience that senior author ( A . B .) has in treat ing this disorder with botulinum toxin. Injection Technique Lyophilized botulinum toxin A (onabotulinum toxin A [BOTOX]; Allergan Pharmaceuticals, Irvine, CA) was obtained and stored frozen at 2 20 C until reconstitution with sterile sa line (without preservative) at the time of injection. The toxin was reconstituted to a concentration of 2.5 units per 0.1 millili ter, where 1 unit represents the median lethal dose (LD50) for mice. Injections were performed by the senior author ( A . B .) using electromyographic (EMG) guidance to place a 27-gauge monopolar, hollow bore Teflon-coated EMG recording needle in areas of maximal electrical activity. Needle placement was con firmed by EMG evidence of voluntary muscle contractions. EMG recordings from musculature contributing to EVT showed regular, 8 Hertz to 10 Hertz contractile activity that was ongoing during both active (e.g., phonation) and passive (e.g. respiration) laryngeal tasks. For a patient with concurrent spas modic dystonia to be included in this series, they had to exhibit clinical and EMG findings of regular tremor present both at rest and with speaking tasks. This is in contrast to pure dys tonic tremor, which does not occur during quiet respiration at rest, and which is usually irregular from agonist/antagonist muscle activity. For predominantly horizontal tremor, thyroarytenoid muscle injections were performed via a transcricothyroid approach. 17 Strap muscles were injected for vertical laryngeal tremor with the needle angled laterally from the midline, piercing the skin at the midportion of the thyroid lamina in the vertical plane. Posterior cricoarytenoid injections were per formed via a retrocricoid approach. 17 Injection regime for patients with both horizontal and vertical tremor depended on the severity of each component. If injection to musculature associated with the more severe tremor component did not provide > 50% symptom improvement by 2 weeks postinjection, musculature associated with the lesser directional movement was injected. If severity of vertical and horizontal components was equivalent, strap muscles were treated first with thyroar ytenoid injections staged 2 weeks later for < 50% symptomatic improvement. Subsequent Injections Patients with < 50% symptomatic improvement on a 1% to 100% of normal function rating scale 2 weeks after initial injec tion were not given any further injections for EVT. Patients exhibiting 50% to 80% response received additional injections into the same muscles, with dose increases of 2.5 units for strap muscles, or 0.25 to 0.5 units for thyroarytenoid muscles unless side effects of initial injection precluded dose increases. Those patients who had > 80% response to initial dose were given the same dose for subsequent injections, with timing of injection based on return of clinical symptoms, usually at 3 to 4 month intervals.

TABLE I. Overall Patient and Disease Characteristics.

N (%)

Gender Male

2 (12.5)

Female

14 (87.5)

Laryngopharyngeal findings Horizontal glottic tremor

15 (93.8)

Vertical tremor

13 (81.2)

Combined horizontal/vertical laryngeal tremor

12 (75)

Tongue base tremor

2 (12.5)

Palatal tremor

1 (6.3) 1 (6.3)

Jaw tremor

Pharyngeal tremor

5 (31.3)

Associated findings Head tremor

5 (33)

Neck tremor

4 (25)

Upper extremity tremor

10 (63)

Coexistent findings of dystonia

8 (50)

Family history

2 (12.5) 5 (62.5)

Alcohol responsive (improvement in symptoms) *

Mean (SD)

Age at symptom onset (years)

64 (12.1)

Duration of symptoms prior to presentation (years) † (only have data for 6/16 subjects)

11.7 (10.7)

*n 5 8 subjects that reported response or lack of response to EtOH. † n 5 6 records that include information regarding symptoms prior to presentation. SD 5 standard deviation.

female and 12.5% had a family history of ET. One sub ject had a twin brother with upper extremity and head tremor, and another subject had a mother and maternal grandmother with head tremor and a daughter with upper extremity and head tremor. Oral medication treat ment history was available for eight subjects and included propanolol, primidone, and anticonvulsants. Oral medications provided good relief of symptoms in about 70% of hand tremors, 60% of head tremors, and less than 50% of vocal tremor. One subject noted some vocal improvement with a regimen consisting of primi done and levetiracetam, while another reported improve ment with amantadine but subsequently developed severe lower extremity edema, necessitating medication withdrawal. Five of eight patients (63%) who consumed alcohol reported improvement in symptoms after use. Clinical Symptomatology Approximately 94% of subjects presented with a component of horizontal glottic tremor on examination and 81% had a vertical component. The majority of sub jects (75%) had both horizontal and vertical tremor. Some patients (31%) were noted to have pharyngeal tremor, creating oscillatory motion in the entire vocal resonating tract. Two subjects presented with tongue base tremor and one patient had coexisting palatal

RESULTS Patient and Disease Characteristics

Patient and disease characteristics are summarized in Table I. Mean age of onset was 64 years (range 35– 81), with a median duration of symptoms prior to pre sentation of 11.7 years. A total of 87.5% of subjects were

Laryngoscope 123: October 2013

Sinclair et al.: Botulinum Toxin Injection for Essential Vocal Tremor

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