Weakness, Dysphagia, and Stridor After Botulinum Toxin Injections

CASE REPORT

Too Much of a Good Thing: Weakness, Dysphagia, and Stridor After Botulinum Toxin Injections

Steven Dominguez, MD, MPH; Marek Dobke, MD, PhD; Steven Dominguez Jr, BS

A 68-year-old woman presented with diminished ability to raise her head, difficulty swallowing, and intermittent stridor 5 days after receiving 225 IU of onabotulinumtoxinA.

Case of treatment, the patient was under the care A 68-year-old woman presented to the ED of a plastic surgeon; thereafter, she sought 5 days after receiving onabotulinumtoxinA treatment at a physician-owned medical cosmetic injections for wrinkles of the face spa because it offered onabotulinumtoxi- and neck. She stated that she was unable nA at a lower price. The injections at the to raise her head while in a supine position medical spa were administered by a physi- and that her head felt heavy when standing. cian assistant (PA). The patient stated that She also experienced spasms and strain although the PA had steadily increased the of the posterior cervical neck muscles. In dose of onabotulinumtoxinA to maintain addition, the patient described a constant the desired aesthetic effect, this was the need to swallow forcefully throughout the first time she had experienced any side ef- day, and felt an intermittent heavy sensa- fects from the treatment. tion over her larynx that was associated The ED staff contacted the medical with stridor. She noted these symptoms spa provider, who reviewed the patient’s began 5 days after the onabotulinumtoxi- medical record over the telephone. The nA injections and had peaked 2 days prior PA stated that he had been the only practi- to presentation. She also complained of tioner at the facility to administer the ona- dysphagia without odynophagia, but de- botulinumtoxinA injections to the patient nied any changes in her voice. over her past 10 years there as a client. He The patient first began onabotulinum- further informed the emergency physician toxinA injections 12 years earlier for (EP) that 12 days prior to presentation, he aesthetic treatment of glabellar and peri- had given the patient a total of 50 IU of orbital wrinkles. She initially received the onabotulinumtoxinA, in five separate in- injections at a regular interval of 90 to 100 jections, into the mid frontalis muscle; a days. During the course of the first 2 years total of 35 IU, in seven separate injections,

Dr Dominguez is a plastic surgeon and retired emergency physician, Bella Milagros Institute, Downey, California. Dr Dobke is professor of surgery, and head, division of plastic surgery, University of California, San Diego. Mr Dominguez is a graduate student, Global Health Sciences, University of California, San Francisco. Authors’ Disclosure Statement: The authors report no actual or potential conflict of interest in relation to this article. DOI: 10.12788/emed.2016.0076

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Regarding the patient’s medical history, she had no health issues suggestive of myasthenia gravis, multiple sclerosis, or Guillain-Barré syndrome. Examination of the face revealed decreased muscle excursion of the frontalis muscle from mid- brow to mid-brow, and stair-step wrinkle formation bilaterally. The procerus muscle was very weak, and the corrugator muscles were moderately diminished in strength. The lateral orbicularis oculi were very weak at each canthus. The extra-ocular muscles were intact. She had full mandib- ular excursion, and powerful movement of the tongue. The oropharynx and floor of the mouth were normal. She was noted to purposefully swallow and extend her © Josep Curto/Shutterstock Figure. Photo (not of the patient discussed in this case report) shows anterior neck neck every 90 to 120 seconds to “clear her platysmal bands of varying length and width. throat,” though she did not drool and was able to handle her secretions and swallow into the glabellar region (procerus and cor- fluids without aspiration. Her voice was rugator muscles bilaterally); 20 IU into the normal and she was able to recite the let- lateral and inferior-lateral orbicularis oculi ters “KKKKK,” “OOOOO,” and “EEEEE” bilaterally, in four separate injections per in rapid fashion without breathiness or side, (40 IU total); and a total of 100 IU in stridor. The rest of her facial muscles were the anterior platysma, in 20 separate injec- normal. tions, for a total 1-day onabotulinumtoxi- While examining the patient, the EP nA dose of 225 IU. asked her to refrain from swallowing The PA explained to the EP that he whenever she extended her neck. Upon mixed the onabotulinumtoxinA in the pa- complying with this request, her neck ex- tient’s room and had shown her the vials tension precipitated swallowing and, by and dilution standard as recommended not swallowing, she did not accumulate by the manufacturer because she had been secretions. Once during the examination, requiring increased dosages and had pre- the patient began swallowing and breath- viously questioned whether the onabotu- ing rapidly with stridor. This less than linumtoxinA was diluted. The PA denied 15-second episode was abated by full-neck any other patients experiencing similar ad- extensions, which relieved the patient’s verse events as those of the patient’s. sensation of heaviness over the larynx. Her Over the last 10 years, the patient had breathing and voice were normal immedi- received onabotulinumtoxinA in the naso- ately after this episode. labial folds, upper and lower lip wrinkles, Examination of the anterior neck re- mentalis, depressor angular oris, buccal, vealed four platysmal bands (Figure). One nasalis, lateral brow, masseter, and calf band measured 10 cm in length and ex- muscles. The dosage of onabotulinum- tended from the mandible inferiorly; two toxinA at this most recent injection cycle bands measured 2 cm lateral to the midline was unchanged from her previous visit 3 bilaterally; and the fourth band extended 4 months prior. According to the PA, the cm in length from the mandible immedi- practice did not use abobotulinumtoxinA ately lateral to the longer platysmal band. or incobotulinumtoxinA. The platysma and dermis were flaccid and

552 EMERGENCY MEDICINE I DECEMBER 2016 www.emed-journal.com redundant at rest and with exertion. The sternocleidomastoid muscles were weak Table. Botulinum Toxins: Clinical Indications with exertion. The larynx moved cephalad with swallowing. The posterior cervical Botulinum Type Indication(s) neck and trapezius muscles were of normal tone and strength. No spasms or fas- Botulinum toxin A ciculations were noted during the exami- AbobotulinuntoxinA Aesthetic wrinkles, blepharospasm, nation period. IncobotulinumtoxinA hyperhidrosis, migraine headache, While supine, the patient strained to laryngeal dystonia, torticollis, and lift her head and complained of a suffo- OnabotulinumtoxinA overactive bladder cating sensation over the larynx. She had no rashes or edema, and the remainder of Botulinum toxin B the physical examination, vital signs, and RimabotulinumtoxinB Adults with cervical dystonia pulse oximetry were normal. Laboratory evaluation, which included a complete blood count and serum electrolytes, was also normal. Discussion An otolaryngologist consultation for la- Clostridium Botulinum Toxins ryngoscopy was obtained. After reviewing Clostridium botulinum is a gram-positive the patient’s case, the otolaryngologist con- spore-forming anaerobic bacterium that cluded that given the patient’s history, in- produces extremely potent neuro-exo- termittent stridor, and an absence of signs toxins. C botulinum is found in soil, con- or symptoms suggestive of an impending taminated foods, and in illicit injectable upper airway obstruction (UAO), laryngos- drugs (eg, heroin). Seven distinct antigen- copy was not warranted. ic botulinum toxins (A, B, C1, D, E, F, and A plastic surgery consultation was then G) are produced by several strains of C obtained. The patient’s examination was as botulinum. Systemically, each neurotoxin noted above, and her vital signs and pulse is able to produce severe morbidity and oximetry remained normal throughout her mortality by causing generalized muscle ED stay. Although botulinum and botuli- paralysis and death by respiratory failure. num antibody titers were ordered, the pa- The lethal dose of these agents is approxi- tient refused testing due to cost concerns. mating 10(-9) g/kg body weight. Botuli- She was discharged home by plastic sur- num toxin type A is the most potent.1,2 gery services with a diagnosis of floppy Nonetheless, botulinum toxin has been neck and dysphagia secondary to aesthetic used clinically since the early 1970s. Cur- botulinum toxin paralysis of the bilateral rently, there are three FDA-approved bot- sternocleidomastoid muscles and platys- ulinum toxin type A agents and one type ma. She was given a prescription for meto- B formulation (rimabotulinumtoxinB) clopramide hydrochloride to stimulate (Table). Each formulation is unique, pro- motility of the upper gastrointestinal tract prietary, and differs in molecular weight, and to potentially improve swallowing.10 toxin-complex size, protein content, and The patient was scheduled for a follow- inactive ingredients. The effectiveness and up evaluation with the plastic surgeon 2 adverse event profile for these four botu- days after discharge. She was instructed to linum toxins is individually dependent call 911 if she experienced stridor, short- upon the different dilutions and potency, ness of breath, drooling, or if any airway onset of action, duration of effect, diffusion, issues arose. The patient did not return for and migration potential. Hence, the effec- her follow-up appointment with the plas- tive dose of one botulinum toxin does not tic surgeon. equate to any other, resulting in a lack of in-

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terchangeability between botulinum toxins been reported in the literature with dos- (eg, 5 IU of incobotulinumtoxinA does not ages ranging from 15 IU to 200 IU used to equal 5 IU of onabotulinumtoxinA). block the Soluble N-ethylmaleimide-sen- sitive factor activating protein receptors. Aesthetic Indications Typical onset of action begins at 3 days, Historically, the use of botulinum toxin for with full paralytic effect at 7 days. Repeat aesthetic treatment of wrinkles and pla- injections every 3 to 4 months are required tysmal bands was first reported by Blitzer3 with prolonged effects seen with each sub- in 1993. Subsequently, the use of botuli- sequent injection due to chemodenerva- num toxin for the aesthetic treatment of tion-induced muscle atrophy.4,7,8 facial wrinkles, hypertrophic platysmal bands and horizontal neck lines gained Adverse Effects popularity within the public and medical Commercial botulinum toxin type A has community.3-5 been associated with minor and transient Anatomically, the platysma is a thin side effects. Moderate complications seen in the neck region include transient soft- tissue edema, dermal ecchymoses, in- The use of botulinum toxin for tramuscular hematoma, diffuse muscle soreness, neck flexor weakness, and head- chemodenervation of the platysma can aches.4,8,9 produce significant weakness The use of botulinum toxin for chemodenervation of the platysma can produce sig- of other neck muscles…. nificant weakness of other neck muscles, including the sternocleidomastoid, crico- thyroid, sternothyroid, and sternohyoid. sheet-like muscle that originates in the su- Floppy neck and dysphagia may be due to perior fascia of the pectoralis and deltoid diffusion of the toxin into the muscles of fascia, and extends over the full length of deglutition of the larynx; injection directly the neck up past the mandible and con- into the sternocleidomastoid muscle; or a tinuing into the submuscular aponeurotic result of the systemic effects of large dos- system. The platysma is innervated by the ages. Hoarseness, breathiness, and dyspha- seventh cranial nerve and functions to pull gia may occur 3 to 4 days after injection, the jaw downward. The platysma muscle especially with doses over 75 IU.10 is attached directly to the skin. With nor- The recommended concentration of mal aging, the anterior neck skin becomes botulinum toxin type A causes a diffusion flaccid, the central platysmal bands thick- average of 1 cm in all directions from the en and contract—forming bands, horizon- injection sites. However, as the dilution in- tal wrinkles, and loss of definition of the creases, so does the zone of diffusion. Typ- neck noticed at rest and with contraction ical discharge instructions for platysma of the platysma muscle. These vertical treatment include the overuse of the neck bands are known as platysmal bands. The muscles for 2 to 4 hours after injection to platysmal bands are benign consequences encourage the botulinum toxin uptake for of aging and as such are targets of correc- optimal result. Site manipulation (rubbing tion through surgery or botulinum toxin or massaging) also increases diffusion. For injection.6,7 botulinum toxin type B, the zone of diffusion is greater because its molecular weight Mechanism of Action is less than the type A toxins, thus making Platysmal band and horizontal line injec- it an undesirable agent for aesthetic facial tion techniques with botulinum toxin have chemodenervation.4,11

554 EMERGENCY MEDICINE I DECEMBER 2016 www.emed-journal.com Toxin Resistance impending UAO may quickly progress Botulinum toxin resistance is a known to complete UAO necessitating emergent complication that occurs normally as a intubation. result of the body recognizing the neuro- An atypical presentation of stridor to the toxin as a foreign substance and produc- ED is sporadic stridor. Sporadic attacks of ing neutralizing antibodies (NAb). Primary stridor during activity have been associ- botulinum toxin failure is known in pa- ated with the entity of paradoxical vocal tients who require high doses of the neu- cord motion. Patients usually describe a rotoxin for treatment of neuromuscular choking sensation with inability to breathe disorders.12 Complete secondary therapy resulting in an audible inspiratory and/ failure is known to occur in cosmetic pa- or expiratory sound—ie, stridor. Wheez- tients after a single dose and those who ing may or may not be present. Patients have been receiving low-dose botulinum may also describe tightness in the neck toxin regularly. The risk of NAb develop- and sometimes in the chest. The attacks ment increases with long-term treatment are usually seconds to minutes in dura- and high doses.12-18 tion. More often, there is a precipitating or an inducing factor such as hyperventila- Floppy Neck and Dysphagia tion, cough, panting, phonatory tasks, or As previously noted, floppy neck and the inhalation of irritants or perfume, or dysphagia are adverse clinical findings of an oropharyngeal or laryngeal manipula- botulinum toxin effect on the platysma, tion prior or postextubation. The feeling of sternocleidomastoid, or the paralaryngeal stress alone is commonly reported prior to muscles. In this case, the patient was for- the attacks. When evaluating patients pre- tunate to have only sustained weakness senting with floppy neck, dysphagia, and of the platysma and sternocleidomastoid stridor, it is imperative that the clinician muscles despite both a large neck and total conduct a thorough history and physical body dose. Paralaryngeal muscle paralysis examination to determine if the symptoms is not life-threatening, but the distress may are secondary to a systemic or local effect, precipitate paradoxical vocal cord motion and whether the patient will progress to an and stridor. acute UAO (vocal cord paralysis) necessitating intubation in the ED and subsequent Stridor tracheostomy.19,20 Stridor is typically a symptom of an upper airway obstruction (UAO) process. Typical Conclusion UAO conditions encountered in the ED are The ready availability of botulinum toxins infections (eg, epiglottitis, croup), foreign and their low-cost-benefit ratio continue body, allergy, and laryngeal trauma. The to promote over-utilization for treatment age of the patient, onset of stridor, course of facial wrinkles, platysmal bands, and of the stridor (ie, intermittent, continuous, horizontal lines; migraine headache; and worsening), associated symptoms (eg, fe- hyperhidrosis. Complications associated ver, rash, swelling of oral soft tissues), and with overuse of botulinum toxins are due bruising must be ascertained. to either administration of a large single In differentiating the etiology of stridor, dose or from regional diffusion. With the the EP should observe the patient for any increasing number of patients receiving associated change in voice, inability to botulinum injections, EPs should be aware handle secretions, and position of com- of the four available toxin types onset of fort. Patients with stridor require admis- action, adverse events, and potential life- sion and evaluation by an otolaryngolo- threatening complications of regional neck gist as expeditiously as possible because injections.

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