Presenters at several scientific sessions at the Combined Otolaryngology Spring Meeting (COSM) reported on their recent studies involving the use of botulinum toxin type A (Botox® [BTX]; Allergan, Inc., Irvine, CA) injections to treat adductor spasmodic dysphonia (ADSD) and chronic salivary aspiration.
Explore This IssueDecember 2007
Botulinum toxin is produced by the bacterium Clostridium botulinum and achieves an irreversible neuromuscular blockade at presynaptic terminals, preventing the release of acetylcholine in response to action potentials.1 BTX cleaves to the SNARE protein, SNAP-25 (integral to the docking/release of acetylcholine vesicles at nerve endings), resulting in flaccid paralysis within a day or two that lasts for approximately three to four months.
During the past two decades, BTX therapy has been increasingly used to treat otolaryngological disorders of excessive or inappropriate muscle contraction before pursuing surgical options. These disorders include:
- Spasmodic dysphonia (adductor or abductor);
- Complex dystonias (oromandibular, laryngeal, cervical);
- Facial hyperkinesias (blepharospasms, hemifacial spasm);
- Vocal tics and stuttering;
- Cricopharyngeal achalasia;
- Various tremors and tics;
- Laryngeal granulomas;
- Posterior glottic synechiae;
- Gustatory sweating;
- Temporomandibular joint disorders; and
- Certain cosmetic applications.2,3,4
Today, BTX injection is considered the gold standard treatment for ADSD, the most common clinical type of spasmodic dysphonia, in which there is increased activity of the vocal fold adductors, characterized by strained and strangled speech with breaks in pitch and phonation. The American Academy of Otolaryngology-Head and Neck Surgery has endorsed BTX injection for spasmodic dysphonia.
A patient with ADSD will feel the clinical effects of a laryngeal BTX injection into the thyroarytenoid (TA) muscle within 24 to 48 hours, but may experience breathiness and occasionally dysphagia for one to two weeks afterward. Symptoms will improve for a period of about two to five months, until new nerve terminals sprout and the muscle returns to its preinjection state and the cycle begins again. Because the effect is temporary, a patient is faced with the lifelong prospect of undergoing an injection procedure every three to four months. There is some concern that repeated injections may cause resistance or irreversible denervation to develop. The dose required for treatment varies due to the accuracy of injection, severity of ADSD, and sensitivity of the patient’s larynx to BTX.5
Because there are few data regarding the long-term dose stability and consistency of BTX in the treatment of ADSD, researchers at the University of California, Irvine, Medical Center conducted a retrospective review of 13 subjects who had received a minimum of six injections (average = 11.5, range 6-19), to establish a baseline set of data to back the widely held belief that BTX dosing is stable in the treatment of ADSD.
Our injection technique is different from most laryngologists, in that it is performed using a percutaneous approach with electromyography [EMG] and flexible fiberoptic videolaryngoscopy for guidance to assure the precision of injection, said the study’s lead author, Paul K. Holden, MD, of the Department of Otolaryngology-Head and Neck Surgery.
-Paul K. Holden, MD
The average total dose of BTX to the larynx for each treatment episode was 3.9 units (range 1.5-7.5). The total dose administered tended to trend downward among patients who began treatment from 1991 to 1998, indicating that the initial dose (usually 2.5 units per side) was often greater than required. Those patients who began from 1999 onward had a more stable dose, indicating that the initial dose (usually 1.5 units per side) was more suitable and improved dosing stability. Subjects underwent an average of 2.2 injections (range 1-5) prior to reaching their optimal BTX dose, defined as the total quantity of BTX injected into the larynx that produced voice quality acceptable to the patient for a minimum duration of three months.6
Greater dose stability is achieved earlier with a smaller initial dose of 1.5 units per side in patients with ADSD, said Dr. Holden. This may also decrease the number of injections required to ascertain a patient’s optimal dose. Dose also depends on the technique used, the type of laryngeal dystonia, and the muscles injected. The initial dose is just a starting point and modifications are made at each subsequent visit based on the patient’s previous response.
Perhaps of equal importance to dose stability is the stability of injection interval, added Dr. Holden. Our study population demonstrates normal variability between injections without any indication of significant and sustained shortening or prolongation.
The total number of treatments performed in this group of patients was 150, with 145 being successful (96.7%). The long-term dosing consistency of BTX (both the dose of BTX to be administered and the interval between injections) confirmed that neither tachyphylaxis (resistance to the effects of the BTX) nor increasing sensitivity to BTX occurred during the course of treatment for ADSD.7
Voice-Related Quality of Life
Another scientific session at COSM addressed the variations in voice-related quality of life (VRQOL) experienced by patients with ADSD after receiving BTX injections, based on a prospective, nonrandomized case series. Researchers from the Washington University School of Medicine in St. Louis collected voice recordings and clinical outcomes data from 22 patients by telephone every two weeks throughout one to three injection cycles (average cycle = 25.9 weeks).
On a 100-point scale, the total VRQOL scores peaked at 77.4 at 30% of the cycle, but then gradually declined. The social-emotional (SE) subscale scores were significantly better than the physical subscale scores (p < 0.05). The total VRQOL score exceeded 75 during only 14% of the cycle (52.6% for SE subscores, 0% for physical subscores).8
If the threshold was lowered to 70, the total VRQOL exceeded this level during 54.6% of the cycle (69.6% for SE subscores, 44.1% for physical subscores). For the 11 patients completing three full injection cycles, there were no significant differences between the three cycles, and the mean VRQOL scores were similar to the values above. At the beginning and end of each cycle, the total VRQOL scores averaged 52.8 (56.0 for SE subscale, 50.7 for physical subscale).9
The researchers concluded that although BTX injections provide significant improvement for these patients, the initial breathy phase and the late declining phase add up to a significant proportion of each cycle spent with a reduced quality of life. Since the total VRQOL averages were below 80% at best, the authors believe that a suitable long-term treatment for ADSD is needed to eliminate the cyclical voice results experienced with BTX therapy.
Until this happens, the dose stability, as well as the initial dose, do improve the breathiness and dysphagia aspects of ADSD, said Dr. Holden. The late declining phase can also be improved insofar as the relative consistency of dose interval can make the return of SD symptoms more predictable.
Chronic Salivary Aspiration
BTX therapy is also being used to reduce sialorrhea, which is a common problem in neurologically impaired children and adults that can lead to chronic salivary aspiration, and subsequently, recurrent aspiration pneumonia.
Although glycopyrrolate, an anticholinergic medication, is still the first choice for patients with chronic salivary aspiration who have no contraindications, certain patients will either develop tachyphylaxis or side effects, requiring that the dose be lowered, said Tejas H. Raval, MD, from the Department of Otolaryngology-Head and Neck Surgery at Tufts New England Medical Center in Boston, during his scientific session presentation at COSM. For these patients, BTX offers an excellent option to either replace the glycopyrrolate or allow better control of secretions with a combined modality treatment that minimizes side effects.
Ultrasound-guided BTX injections into the bilateral submandibular and parotid glands block the parasympathetic innervation of salivary glands, resulting in a temporary decrease in saliva production and improved quality of life.
This is a technically simple procedure with no reported side effects, which can be done under minimal sedation or local anesthetic at the bedside, resulting in little to no postoperative pain or recovery period, added Dr. Raval. The main disadvantage is that the effects last from only 8 to 12 weeks and must be repeated at this interval to maintain optimal efficacy. This is a very important point to stress to the patient and family.
-Tejas H. Raval, MD
As few reports exist regarding the efficacy of this treatment in the prevention of recurrent aspiration pneumonia, Dr. Raval performed a retrospective chart review of 12 patients (7 months to 37 years of age) treated with BTX injections at a single tertiary care institution, as well as a caregiver telephone questionnaire. The number of pulmonary infections and hospitalizations before and after the initiation of treatment were compared.
Nine of the 12 patients experienced improvement in both the number of diagnoses of aspiration pneumonia and of hospital admissions before and after BTX therapy. Of the nine patients showing improvement, the average yearly episodes of pneumonia or lower respiratory tract infection improved from 4.2 (± 3.2) to 1.0 (±0.7). The same group showed an improvement in hospital admissions for aspiration pneumonia from 1.8 (±1.7) to 0.3 (±0.7). Improvements in anticholinergic medication use and pulmonary toilet requirements were also noted and there were no complications of treatment.10
Based on his research, Dr. Raval concluded that BTX injection into the major salivary glands could be a viable option for many neurologically impaired patients for the treatment of chronic salivary aspiration and recurrent aspiration pneumonia. It may allow for a reduction in anticholinergic medications and obviate the need for surgery. For patients who respond well to BTX treatment, there is the potential to improve pulmonary health, as well as both patient and caregiver quality of life, through regularly repeated injections.
We hope to investigate this treatment prospectively and determine whether patients who do not respond well to treatment may do so with a higher dosage, said Dr. Raval.
- Lange DJ. Systemic effects of botulinum toxin. In: Jankovic J, Hallett M, eds. Therapy with Botulinum Toxin. New York, NY: Marcel Dekker, 1994:109-18.
- Blitzer A, Sulica L. Botulinum toxin: basic science and clinical uses in otolaryngology. Laryngoscope; 2001;111(2):218-26.
- Rohrbach S, Laskawi R. Botulinum in ENT medicine. Laryngorhinootologie 2003;82(3);202-13.
- Yin S, Stucker FJ, Nathan CO. Clinical application of botulinum toxin in otolaryngology, head and neck practice (brief review). J La State Med Soc 2001;153(2):92-7.
- Holden PK, Vokes DE, Taylor MB, Till JA, Crumley RL. Long-term botulinum toxin dose consistency for the treatment of adductor spasmodic dysphonia. Abstract presented at the Combined Otolaryngology Spring Meeting (COSM), April 26, 2007.
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- Paniello RC, Barlow J, Serna JS. Longitudinal follow-up of adductor spasmodic dysphonia patients following botulinum toxin injection: quality of life results. Abstract presented at the Combined Otolaryngology Spring Meeting (COSM), April 29, 2007.
- Id. [Context Link]
- Raval TH, Elliott, CA. Salivary aspiration: a role for botulinum toxin treatment to the salivary glands. Abstract presented at the Combined Otolaryngology Spring Meeting (COSM), April 26, 2007.
©2007 The Triological Society