Selective chemodenervation with botulinum toxin in facial nerve disorders

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Operative Techniques in Otolaryngology (2012) 23, 297-305

Selective chemodenervation with botulinum toxin infacial nerve disorders

Jon-Paul Pepper, MDa,b, Jennifer C. Kim, MDa,b

From the aDepartment of Otolaryngology, Head and Neck Surgery, University of Michigan Hospital and Health Systems,Ann Arbor, Michigan; and
bCenter for Facial Cosmetic Surgery, University of Michigan, Livonia, Michigan.
Selective chemodenervation is an important adjunct in the management of several aspects of facialnerve paralysis and paresis. Herein, the authors describe the utility of chemodenervation in thetreatment of the synkinesis and contralateral hyperkinesis often associated with facial nerve injury.© 2012 Elsevier Inc. All rights reserved.

KEYWORDSBotulinum toxin;Facial paralysis;Synkinesis

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Dr Alan Scott is credited with the discovery of purifiedbotulinum toxin for selective chemodenervation, first usedin 1977 to treat strabismus.1 As is now widely known, theuse of botulinum toxin expanded drastically in the 1990s forthe temporary treatment of facial rhytids. The earliest pub-lished report of botulinum toxin used for the treatment offacial rhytids included a patient with partial facial nerveparalysis after rhytidectomy.2 The asymmetry caused by thentact (contralateral) frontalis, corrugator, and depressor su-ercilii muscles prompted the patient to seek evaluation.iven the patient’s distress over the resultant facial asym-etry, the surgical team obtained a compassionate-use ex-

ension for off-label use of the drug from the US Food andrug Administration in 1987. This group subsequently pub-

ished the positive results of this trial in 1989.2 Therapeuticapplication for oral–ocular synkinesis was first reported in1989 by May et al, with excellent preliminary results.3

Several other groups reported successful temporary treat-ment of synkinesis with botulinum toxin shortly thereaf-ter.4,5

The sequelae of facial nerve paralysis are broad and havea significant impact on patient quality of life.6 These mayinclude, but are not limited to, altered resting and dynamicfacial esthetics, difficulty expressing emotion, speech im-

Address reprint requests and correspondence: Jon-Paul Pepper,MD, Center for Facial Cosmetic Surgery, 19900 Haggerty Road, Suite 103,Livonia, MI 48152.

sE-mail address: [email protected].

1043-1810/$ -see front matter © 2012 Elsevier Inc. All rights reserved.http://dx.doi.org/10.1016/j.otot.2012.10.001

pairment, chewing difficulties, lagophthalmos, ectropion,and hyperlacrimation.7 This large array of maladies can beenerally attributed to 3 main pathologic mechanisms: theenervated ipsilateral facial nerve, synkinesis of a nerveith paresis or partial recovery from complete paralysis,

nd contralateral hyperkinesis.Contralateral hyperkinesis, or compensatory contralat-

ral contraction, refers to the exaggerated contraction of thentact side of the face, which is thought to be both a behav-oral and reflex adaptation that attempts to compensate forhe paralyzed side.7,8 (Figure 1). The lack of an intact

uscular opponent causes overcontraction of the intactide,8 particularly during the expression of emotion. This

overcompensation is a key component of the overall facialdisharmony that results from facial nerve paralysis. Inter-estingly, there appears to be a neural reorganization thatheightens not only willful contraction but also contralateralreflex responses.9 The degree of contralateral neural reor-anization may even correlate with the severity of the ipsi-ateral lesion.9

Crumley defined facial synkinesis as the unintentional mo-tion of one area of the face that occurs as a result of intentionalmovement of another.10 After nerve trauma, axons projectrom the facial nucleus and throughout the length of the nerveo “incorrect” peripheral muscle groups.7 For example, a por-ion of the axons that innervate the orbicularis oris aberrantlyegenerates and innervates the orbicularis oculi. A common
ynkinetic muscle pattern involves cocontraction of the oculi
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http://dx.doi.org/10.1016/j.otot.2012.10.001

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298 Operative Techniques in Otolaryngology, Vol 23, No 4, December 2012

muscles and mentalis with smile and activation of platysmalmuscle with smile (Figure 2).

It has been proven to cause significant functional andsocial debility, and may furthermore be associated withpain.1 In the senior author’s (J.C.K.) clinical practice, weave noted that unrehabilitated synkinesis rarely improvespontaneously. Additionally, the location of facial nervenjury is thought to be an important predictor of synkinesiseverity.11 The intratemporal facial nerve has little somato-opic organization, whereas the facial nerve develops a morelearly demarcated somatotopic arrangement as it courseshrough and ultimately exits the temporal bone.11 Rates ofynkinesis after facial nerve injury are therefore quite vari-ble, with intratemporal injury producing much higher ratesf synkinesis compared with extratemporal facial nervenjury. After Bell palsy, the incidence of synkinesis haseen estimated at 15 to 20%.12 Conversely, a series of 30

cases of facial nerve injury during acoustic neuroma resec-tion with subsequent suture repair produced clinical evi-dence of synkinesis in almost all patients.13 This illustratesthe working concept that more proximal injuries may beassociated with more severe synkinesis.

Most commonly, synkinesis becomes clinically evident 3to 4 months after nerve injury, but has been reported as earlyas 6 weeks after injury.12 The definitive neurophysiologicmechanism is incompletely understood; however, a growingbody of evidence indicates that aberrant regeneration ofinjured axons is the most likely etiology.14

The clinical evaluation of synkinesis has, at present, nouniversally accepted gold standard. However, there are avariety of useful assessment tools. Two of the most com-monly used scales are the Facial Nerve Grading Scale 2.0and the Sunnybrook Facial Grading System.15,16 Bothscales evaluate facial nerve paresis and synkinesis simulta-neously. Both use 4-point Likert scales that analyze synki-nesis at each major muscle group of the face. Clinical

Figure 1 Photograph of a patient with right-sided facial paraxaggerated contraction of the intact side of the face, which is thougs available online.)

observer’s assessment of synkinesis is by no means straight-

forward; this point is underscored by a recent electromyo-graphic study that found that observers scored orbicularisoculi movement when the electromyography in fact de-tected no electrical activity in this muscle group.17 There-fore, subjective patient scales have also been developed,such as the Synkinesis Assessment Questionnaire, and somepractitioners use these exclusively.18

Although the consideration of contralateral hyperkinesisand synkinesis as separate entities is technically accurate, thepatient with an incompletely recovered facial nerve injuryoften features a mélange of ipsilateral synkinesis andcontralateral hyperkinesis. Botulinum toxin has beenproven to be highly effective in the treatment of con-tralateral hyperkinesis8,19 as well as synkinesis.20 Signif-cant improvements in patient quality of life have beeneported when using botulinum toxin to address bothynkinesis and contralateral hyperkinesis. The beneficialffects of botulinum toxin are detectable at approxi-ately 1 week, peak at approximately 4 weeks, and

ersist for approximately 3 months.8

Methods

The mechanism of paralysis is carefully explored during thepreoperative history taking and physical examination. Thetiming of the initial injury, if known, will at least in partdictate the expected recovery schedule, thereby determiningthe appropriate timing of treatments. In addition to themechanism of paralysis, the age of the patient is a criticalcomponent of the degree of neuromuscular tone the surgeoncan expect, which can have a dramatic effect on treatmentoutcomes. Any previous rehabilitation or reanimation ef-forts are noted. Many patients with complete paralysis willundergo reanimation procedures, either static or dynamic;botulinum toxin has been shown to be an effective adjunct

t rest and then with a gentle and exaggerated smile. Note thee reflexive compensation for the paralysis. (Color version of figure

lysis aht to b

in these patients.21

299Pepper and Kim Selective Chemodenervation with Botulinum Toxin in Facial Nerve Disorders

Patients are specifically questioned if they have a historyof chronic neurodegenerative conditions (such as myasthe-nia gravis or muscular dystrophy), symptomatic dry eyesyndrome, or preexisting neuromuscular ptosis. Althoughthere are no known case reports of adverse reactions inpregnant women, it is our practice to eschew the use ofbotulinum toxin in pregnant or women who are breast-

Figure 2 (A) A common synkinetic muscle pattern involves sitethering fasciculations of the mentalis, and activation of platysmalafter Botox treatment. (B) Schematic illustration of the individudepressor labii inferioris; FRO, frontalis; MEN, mentalis; OCSorbicularis oris superioris; OOI, orbicularis oris inferioris; PRO, pzygomaticus minor. (Color version of figure is available online.)

feeding. Any patients with a history concerning for occult

dry eye syndrome or progressive myopathy are referred forappropriate evaluation before treatment.

A careful physical examination is performed. This in-cludes detailed photodocumentation and videography. Ananalysis of the patient’s face in repose is first performed.Note is made of any resting asymmetries before volitionalmovement. The patient is then asked to perform a series of

on activation of the orbicularis oculi muscles narrowing the eye,with smile. The photograph on the right shows the patient smiling

al muscles. COR, corrugator; DAO, depressor anguli oris; DLI,ularis oculi superioris; OCI, orbicularis oculi inferioris; OOS,s; PLA, platysma; RIS, risorius; ZYJ, zygomaticus major; ZYN,

mulatimuscleal faci, orbicroceru

facial movements: brow elevation, full smile, half smile,


lips pursed, showing lower teeth to activate depressors, fulleye closure (hard blink or squint), and passive blink. Ob-taining video footage of the patient in ordinary conversationis always very helpful in evaluating the patient’s synkineticmovements. The patient signs informed consent for all in-jections.

Figure 3 A copy of our Botox treatment record sheet. The units
circled in the calendar and marked on the corresponding face. This reco
All our patients are referred for facial rehabilitation beforeany botulinum toxin treatments. One of the primary goals offacial rehabilitation, although often the most overlooked one, issynkinesis management. Specific neuromuscular reeducationexercises teach the patient how to symmetrically move thefacial muscles, while simultaneously controlling associated

ritten on the face over the area injected, and the date of treatment
are w rd provides a good visual aid of the treatment regimen given.


synkinesis.22 Additionally, soft-tissue mobilization and relax-ation techniques are taught to facilitate the control over synk-inesis. It is important to educate the patient on the anatomy andfunction of their individual facial muscles, given the criticalneed for patient engagement in facial rehabilitation on theirown at home. Figure 2B shows a detailed schematic illustrationof the various facial muscles.

Botulinum toxin is used to release synkinesis in targetedregions, mainly the orbicularis oris, mentalis, and platysma.Usually, the intact frontalis and depressor labii inferior areinjected to achieve symmetry at rest for forehead rhytids andsymmetrical coverage of the lower dentition during smiling,respectively. Contralateral lower lip weakening also provides amore symmetrical appearance during articulation. Figure 3shows an example of a Botox treatment document to recordBotox injection doses and sites on a calendar.

Figure 4 shows a patient with a history of Bell palsy whorecovered facial nerve function with significant synkinesis.The left photograph shows the patient in repose, and theright photo shows the patient when asked to smile. Themarkings show typical synkinetic patterns that develop.Starting from top to bottom, the frontalis muscle on theaffected side typically does not elevate on attempt to raiseone’s brows, but will show some contraction when trying toclose one’s eyes. There is corrugator asymmetry, whichcontributes to brow asymmetry. The palpebral fissure nar-rows with smile or lip pucker. There is tightness of theaffected midface, often accompanied by a deeper nasolabialfold at rest, thickened foreshortened muscles on bimanualpalpation of the cheek, and subjective complaint of discom-fort in the area. With the attempt to smile, there is poorexcursion of the modiolus, which is also deterred by acti-

Figure 4 Photographs of a patient with synkinesis after Bell palpatient is attempting to smile. The yellow arrow on the forehead sshows the palpebral narrowing. The arrows on the lower face showis available online.)

vation of the platysma. The depressors do not activate as

they do contralaterally, and the mentalis activates only onthe synkinetic side. The asymmetry becomes magnifiedwith a greater attempt to smile, as the intact side overcom-pensates for the synkinetic side.

Figure 5 shows the same patient at repose before and 2weeks after Botox treatment. Even at repose, there is adramatic change in the overall harmony and balance to herface. Figures 6-8 illustrate the injection sites and amounts ofBotox to address the patient’s synkinesis. It is important torealize that both halves of the face are affected, and even theso-called normal intact side needs to be treated and evalu-ated as closely as the synkinetic side.

We find it very useful to break the face up into zones forevaluation and treatment. In Figure 6, the forehead is ad-dressed. The asymmetric brow elevation is obvious, butwhat is not so evident is a baseline hyperkinetic state of thesynkinetic brow. Most patients’ brows on the affected sidesit at a higher position at rest and fail to elevate with thecontralateral brows, but instead may elevate when smilingor squinting. Treating the entire forehead addresses all thesedisharmonious movements.

Then, focus is on the periorbital region (Figure 7),which is also affected by the midfacial muscles. In mostpatients, the affected eye narrows with smiling or lippuckering. Importantly, the pretarsal orbicularis contrib-utes mostly to the palpebral narrowing, and so it is moreeffective to inject small doses of Botox closer to theupper and lower lid margins. If there are prominentlateral orbital rhytids on the intact side, a small dose isinjected to weaken them for symmetry.

The midface is the most difficult area to treat with Botox(Figure 8). Injections to the midfacial muscles often help

left photograph shows the patient in repose, and on the right, thehe ipsilateral frontalis activation with smiling. The yellow bracketlis and platysmal activation with smiling. (Color version of figure

sy. Thehows t

menta

reduce pain associated with muscle tightness, but also risk

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dropping the upper lip and worsening the smile. Often,small doses injected near the nasalis muscle help those withdiscomfort, without unwanted side effects. The asymmetryof the nasolabial folds is best addressed with a filler toefface the synkinetic side. Those with significant overcom-pensation of the smile on the intact side may benefit fromslight weakening of the zygomaticus on the intact side.

The lower face and neck is the last zone (Figure 9).Characteristic findings with smile include depressor asym-metry with absent depressor movement, mentalis activation,and strong platysmal activation on the synkinetic side. Thiszone is best treated by weakening the intact depressor, the

Figure 5 Photographs of the patient at repose before and 2 we

Figure 6 Photographs of the patient before and after Botox tre
line.)
entire mentalis, and the abnormal platysma. Patients shouldbe forewarned that they will have to adjust to the changesperiorally, especially after weakening the depressor. Evenwith some weakening of the orbicularis oris muscle, it israre to cause perioral incompetence.

Lyophilized botulinum toxin type A (Allergan, Inc), 100units per vial, is diluted to a concentration of 5 units per 0.1mL with preservative-free sterile saline. A 32-gauge hypo-dermic needle and a 1-mL syringe are used. Before injec-tion, the skin is sterilized with an alcohol pad, and patientsare offered topical anesthetic cream, although this is rarelynecessary. Figure 3 shows an injection diagram of a patient

er Botox treatment. (Color version of figure is available online.)

t to the forehead zone. (Color version of figure is available on-
atmen


with severe right-sided synkinesis and mild left-sided com-pensatory hyperkinesis. The figure legend details the injec-tion volumes for each major muscle group.

After injection, light pressure is held on the injectionsites, with ice packs for comfort. The patients are scheduledfor a return visit at approximately 7 days and then severalmonths after surgery. The benefit of botulinum toxin injec-tions is appreciable after 3 to 5 days, with additional injec-tions performed as necessary. The benefit wanes after 3months, and we routinely conduct patient follow-ups 2 to 3months after injection to assess their progress.

Figure 7 The panel at left shows the number and distribution oat right shows the patient after the botulinum injections at approonline.)

Figure 8 Photographs showing the improved symmetry of the mi
version of figure is available online.)
Complications

Complications of botulinum toxin injection are rare at thedoses used for chemodenervation of facial musculature, andthere have been no reported deaths from cosmetic facialinjection despite �25 years of use in humans.23 A Cochranereview has demonstrated that the medication is safe andeffective; the majority of reported adverse events are mildor moderate in terms of clinical severity.24 The most com-mon adverse reactions are local tissue responses such aspain, edema, erythema, ecchymosis, headache, and short-

otulinum toxin units used to treat the periorbital zone. The panelly 2 months post-treatment. (Color version of figure is available

nd vector of the upper lip before and after Botox treatment. (Color

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term hyperesthesia.24 Authors have rarely reported systemicreactions such as nausea, fatigue, malaise, flu-like symp-toms, rash, or a metallic taste.23 Allergic reactions to botu-inum toxin used in facial cosmetic procedures are rare.23

Most commonly, systemic reactions to injection have oc-curred outside the dosages commonly used in facial plasticsurgery. It should be noted for reference that the Food andDrug Administration–approved dose for the use of Botox inthe treatment of glabellar furrows is a maximum of 20 U ofbotulinum toxin type A per session.25

The most common adverse event from botulinum injec-tion in facial plastic surgery is unintended migration of thetoxin from the target muscle to unintended muscle groups.23

Ptosis of the brow, lip, and eyelid have been described, anddiplopia can result if botulinum toxin diffuses to the extrin-sic muscles of the eye.

Similarly, eye pain and dry eye can occur from inadver-tent infiltration of the toxin into the lacrimal gland or itspostganglionic parasympathetic innervation.26 Compared

ith serotype A, serotype B has been associated withreater autonomic side effects, such as dry mouth, anhidro-is, dysphagia, constipation, pyrosis, urinary retention, andonjunctivitis.27

Conclusions

In the senior author’s clinical practice, botulinum toxin is asafe and powerful adjunctive treatment for patients withfacial nerve paralysis and synkinesis. It is currently the mosteffective treatment for synkinesis, with the main drawbackbeing its gains are inherently temporary and require retreat-ment. Of paramount importance is the integration of con-

Figure 9 The panel at left shows the number and distribution opanel at right shows the patient after the botulinum injections at apponline.)

current facial neuromuscular therapy to achieve longer-

lasting and satisfactory improvement. The observed level ofsatisfaction has been high, with minimal to no risks andcomplications. Selective myectomy, selective neurectomy,and cross-facial nerve grafting with secondary microcoap-tations have also been reported in the literature and mayoffer more long-term treatment options.28-30

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3. May M, Croxson GR, Klein SR: Bell’s palsy: management of sequelaeusing EMG rehabilitation, botulinum toxin, and surgery. Am J Otol10:220-229, 1989

4. Roggenkämper P, Laskawi R, Damenz W, et al: Involuntary lid clo-sure caused by defective healing of facial paralysis and its treatmentwith botulinum toxin. Klin Monbl Augenheilkd 198:268-270, 1991

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otulinum toxin units used to treat the lower third of the face. Theately 2 months post-treatment. (Color version of figure is available

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19. Bikhazi NB, Maas CS: Refinement in the rehabilitation of the para-lyzed face using botulinum toxin. Otolaryngol Head Neck Surg 117:303-307, 1997

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22. Brach JS, VanSwearingen JM: Physical therapy for facial paralysis: atailored treatment approach. Phys Ther 79:397-404, 1999

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24. Naumann M, Albanese A, Heinen F, et al: Safety and efficacy ofbotulinum toxin type a following long-term use. Eur J Neurol 13:35-40, 2006

25. Coté TR, Mohan AK, Polder JA, et al: Botulinum toxin type a injec-tions: adverse events reported to the US Food and Drug Administrationin therapeutic and cosmetic cases. J Am Acad Dermatol 53:407-415,2005

26. Ferreira MC, Salles AG, Gimenez R, et al: Complications with the useof botulinum toxin type a in facial rejuvenation: report of 8 cases.Aesthet Plast Surg 28:441-444, 2004

27. Dressler D, Eleopra R: Clinical use of non-A botulinum toxins: bot-ulinum toxin type B. Neurotox Res 9:121-125, 2006

28. Guerrissi JO: Selective myectomy for postparetic facial synkinesis.Plast Reconstr Surg 87:459-466, 1991

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Selective chemodenervation with botulinum toxin in facial nerve disorders