TOPICS

A Novel Long-term Therapy of Facial Synkinesis with Botulinum Neurotoxins Type A and Fillers

Adam Wiener, DO; Khasha Touloei, OMS3; Bradley P. Glick, DO, MPH, FAOCD

Adam Wiener, DO, and Bradley P. Glick, DO, MPH, FAOCD, are from Wellington Regional Medical Center, Wellington, Florida. Khasha Touloei, OMS3, is from Western University of Health Sciences, Pomona, California.

Disclosure: The authors report no relevant conflicts of interest.

Abstract
Facial synkinesis is the involuntary movement of facial muscles accompanying a voluntary movement. It is a common sequelae to Bell’s palsy. The authors present a 50-year-old patient who developed facial synkinesis after Bell’s palsy. Pain, discomfort, and facial asymmetry accompanied the condition. She was treated on multiple occasions with neurotoxins and fillers over a period of six years. During this time she reported great improvement in the pain of the affected area, along with an acceptable improvement in the cosmetic appearance of her face. The hope is that in the future, fillers as well as toxins may be utilized in combination to improve and restore the quality of life in people who suffer from similar disfiguring diseases and events.  (J Clin Aesthet Dermatol. 2011;4(3):45–49.)

The authors present the case of a 50-year-old woman who developed a right-sided Bell’s palsy in 2002, resulting in synkinesis with right-sided facial spasms 2 to 3 months after the initial diagnosis. Most notable was the contraction of her right platysma muscle in conjunction with blinking. This led to muscle soreness and pain in her neck due to the repetitive contractions throughout the day. An unresolved facial asymmetry accompanied the discomfort. She was diagnosed by a neurologist after a detailed neurological evaluation and further testing, including magnetic resonance imaging that proved to be negative. Initial therapy included valcyclovir and prednisone.

Pain control in the first year consisted of nonsteroidal anti-inflammatory drugs (NSAIDs) and opiates, which provided inadequate relief according to the patient. In 2003, she was injected with onabotulinumtoxinA (BTX-A) into her platysmus muscle, which greatly reduced her symptoms and contractions. Over the ensuing two years, she received sporadic, but similar, treatments, as she was inconsistent with her follow-up appointments and there was a paucity in the insurance coverage for these procedures.
She presented to the authors’ dermatology office in July 2005, where she stated that her asymmetry had worsened. The muscles of her affected, synkinetic right side had become hypertrophic from their hyper functional contractile state, resulting in an increased fullness and a reduced facial mobility on that side. Her main objective was to decrease the pain associated with the muscle spasms and to improve her facial symmetry (Figures 1A and 1B).

Hyaluronic acid gel fillers in addition to BTX-A were originally injected in an attempt to correct her asymmetry and facial spasms, respectively. A total of two cc’s of Restylane were injected in the nasolabial grooves, marionette lines, and lips. The majority of the product was injected on the left, unaffected side to create more balance in her face. Likewise, the injection of BTX-A was administered to the platysma and mentalis muscles for the aberrant contractions. Twenty-four units of onabotulinumtoxin were injected into the right platysma muscle with another 12 units injected into the left side. A total of 10 units were injected into the mentalis muscle (6:4; R:L). The unit dosage was much greater on the affected, right side. Two weeks after the injections, the patient reported great satisfaction in both the improvement of her symptoms and a global improvement in the appearance of her facial symmetry.

The patient returned in February 2006. She stated that most of the improvement subsided to baseline by six months after the last treatment and she inquired about more long-term results. Sculptra was chosen as a longer term filler option. This was injected into her left malar cheek and nasolabial folds (6cc dilution) to create a balancing lifting affect (Figures 2A and 2B). She returned in May for a second vial of Sculptra. BTX-A was re-injected during both of these visits in the same quantities as in the previous visit. Once again, the patient felt positive about her results. Her symmetry was most normalized at rest. She continued to exhibit some dynamic asymmetry with movement.

She returned a final time in September 2009 to discuss additional filler options. She was seeking a filler option with greater longevity and immediate effects. During this visit, the goal was more of a robust volume filling, which, in turn, led the authors to pick three 1.5 syringes of Radiesse diluted with 0.3cc 1% lidocaine. The majority was injected into her left mid- and lateral cheeks, nasolabial fold, and marionette line. In addition, a 1cc syringe of Restylane was also injected into her lips.  BTX-A was re-injected into her platysma and mentalis muscles and additionally into her glabella, orbicularis oculi, nasalis, and depressor anguli oris (Figures 3A and 3B).
Over the course of the treatment period, the patient experienced significant weight gain. This weight gain did not compensate for her persistant facial asymmetry, and hence, the multitude of treatments to improve the more apparent dysmmetries of her condition. Her treatments improved her asymmetry substantially and the toxins were of great help to reduce the discomfort associated with muscular spasms. She reports a greatly improved quality of life as a result of the treatments (Figure 4).

The aim of this paper is to promote the use of fillers and toxins in combination to improve and restore the quality of life in people who suffer from similar disfiguring diseases and events.

Discussion
Facial synkinesis is an abnormal involuntary movement of one set of facial muscles accompanying a voluntary movement of a different facial muscle. These unintended movements stem from a damaged or compressed facial nerve that has not regenerated properly and appear as a late sequela to a spontaneously healing facial nerve injury. This, in turn, can affect daily activities and functioning, and individuals suffering from this condition can be affected aesthetically and experience social isolation. Facial asymmetry affects the cosmetic appearance and can lead to the misinterpretation of specific emotional expressions.[1] An individual may struggle to convey specific emotional expressions due to unintended movements. The most common presentation of facial synkinesis is oculo-oral synkinesis, which occurs when a patient who closes his or her eye voluntarily has a subsequent involuntary movement of his or her mouth.[2] Other presentations of facial synkinesis include midfacial muscle contraction during voluntary closure of the eye, narrowing of the eye, lifting the brow, lifting the corner of the mouth, chin dents, and platysma contraction when voluntarily smiling.[1,3]

There are many different causes of facial nerve paresis. Most frequently, it is a common sequela to idiopathic facial nerve paralysis, also called Bell’s palsy or facial palsy. Other causes include trauma and infections.[4] Transcutaneous electrical nerve stimulation (TENS) units, electrical stimulating devices that are sometimes used to treat facial nerve palsy, have also been shown to be disruptive to the normal re-innervation process and can potentially lead to the development of synkinesis.[5] Synkinesis can also occur following reconstruction of the facial nerve in patients suffering from malignant tumors of the parotid gland.[6]

Pathogenesis
There have been several proposed mechanisms for the development of synkinesis. The most commonly accepted explanation is that when a nerve regenerates, it undergoes aberrant regeneration, which may accidently innervate additional neighboring muscle fibers.[7] This phenomenon of regenerative nerves sprouting into the wrong peripheral branches is known as the Lipschitz theory.[8–11] Fifteen to 20 percent of patients will experience synkinesis after a facial nerve paralysis.[12–13] If synkinesis is present, complete recovery is unlikely.[7]

Treatment
Established treatments for facial synkinesis include surgical treatment such as neurolysis or myectomy,[7,8] neuromuscular retraining,[14–16] mime therapy,[17,18] trans-mastoid decompression,[19] biofeedback rehabilitation,[20–22] and BTX-A. Currently, the most common therapeutic modality is BTX-A, making surgery a much less commonly performed treatment alternative.[7]

BTX-A is produced by bacterium Clostridium botulinum[24] and works by inhibiting the release of acetylcholine from the presynaptic motor end plate. This, in turn, prevents muscular contraction,[6] explaining why it is a successful treatment of facial synkinesis. Muscle function can recover using BTX-A secondary to the neurogenesis phenomena. Formation of new axonal sprouts, new plates, nervous terminations, and the absorption of devitalized neurons requires several treatments to fully denervate the muscle.

Botulinum toxin A has been used for many years in different facial diseases. BTX-A was first used in 1979 to correct strabismus by injecting the toxin into external eye muscles.[25] Throughout the 1980s, it was used to treat blepharospasm and hemifacial spasm.[7] The application of BTX-A can improve movement and facial asymmetry disorders, such as blepharospasm, hemifacial spasm, synkinesis following defective healing of the facial nerve, palatal tremor, severe bruxism, and oromandibular dystonias hypertrophy of the masseter muscle. Furthermore, it can be used for disorders of the autonomic nervous system, such as hypersalivation, hyperlacrimation, pathological sweating, and intrinsic rhinitis.[6]

The first use of BTX-A therapy for facial synkinesis was in 1990.[26,27] Since then, there have been many published reports of BTX-A therapy used for facial synkinesis.[26–30] Most of the literature shows facial synkinesis resolving within a few days of injection. The published reports all show that the treatment remains effective for 3 to 7 months. The majority of the studies did not have any significant complications. Ptosis was slightly more frequent in some of the reports.

Laskawi et al[6] inject BTX-A using six injection points around the eye to reduce synkinesis of the orbicularis oculi muscle using dosages from 1.25 to 5 units (Botox) on each injection point. The authors found that lower dosages are necessary to treat synkinesis compared to other facial dyskinesis, such as hemifacial spasm or blepharospasm. The report also indicates BTX-A was used on patients with synkinesis of the platysma muscle and was proven to be effective.[6] The Arikan et al study shows how 50 units of BTX-A can be used to treat hypertrophy of the masseter muscle, which also significantly produces facial asymmetry.[31]

Roggenkamper et al[32] demonstrated the efficacy of BTX-A for facial synkinesis in a study of 23 patients with orbicular synkinesis who were all treated with BTX-A. All patients had 13 symptom-free weeks, followed by a period of minimal symptoms.[32]

Most promisingly, Armstrong et al[27] studied the treatment of 24 patients with facial synkinesis and facial asymmetry with BTX-A following facial nerve palsy, specifically the eye and mouth areas. The results found that 68 of 72 treatments had produced improved cosmesis. Dose-related complications occurred in 26 treatments, but were generally mild and transient. The higher dose group seemed to offer no significant advantage over the lower dose group in the overall cosmetic improvement. However, the complication rate was significantly higher in the higher dose group (20/39) compared with the latter (6/33).[27]

Itol et al[33] performed a study of 11 patients suffering from facial synkinesis after Bell’s palsy or facial nerve injury. The patients were injected with a low dose of BTX-A, 0.5 to 1.25 units per point, into several points over a period of 43 months. On average, 5.76 units of BTX-A were used per visit. In seven cases, synkinesis disappeared completely after three or fewer sessions of BTX-A injection. The mean interval between treatments was 14.5 weeks.[33]

Chua et al[3] conducted a study with five patients suffering from eyelid synkinesia and treated with injections of either 120, 80, or 40 units of BTX-A (Dysport) into the orbicularis oculi. All five patients demonstrated improvement of synknesia. Furthermore, the study indicated that lower doses were found to be as effective as higher doses. Two of the five patients developed a ptosis that resolved spontaneously. The three patients treated with the lowest dose of 40 units developed a ptosis.[3]

Borodic et al[34] performed a double-blind, placebo-controlled trial assessing the efficacy of BTX-A of 36 patients treated with either 10 units of Botox or preservative-free saline (control). Both subjective and objective improvements were achieved in all patients treated with BTX-A therapy as compared to placebo.[34]

There have been multiple controlled trials showing the safety and efficacy of botulinum toxin A for aberrant nerve regeneration. However, at the time of this submission, there was only one cited article using fillers in a patient with Bell’s palsy and none combining the use of neurotoxins with fillers for synkinesis associated with Bell’s palsy. Mancini et al[35] evaluated the efficacy of hyaluronic acid gel fillers as a nonsurgical alternative for the management of upper eyelid margin asymmetry, showing statistically significant improvement in symmetry. The study indicates that facial asymmetry can be improved with hyaluronic acid gel filler.[35]
BTX-A is a recognized and accepted treatment for neuromuscular disorders and can provide nice effects on those patients for whom it is used. The case described here also demonstrates the effective use of several different fillers for the same condition, which led to similar satisfactory results for the patient. In conclusion, BTX-A and fillers are a safe, easy to use, and effective option in the management of facial synkinesis and asymmetry. Its use is associated with a high degree of patient and physician satisfaction.

Further studies and reports may be needed to justify the use of these expensive products; however, the potential benefit was confirmed by both the clinical improvement and the patient’s satisfaction in this case. The authors’ hope is that, in the future, fillers and neurotoxins may be utilized in combination in a medical fashion to help improve and restore the quality of life among people who suffer from disfiguring diseases and events.

References
1.    Beurskens CHG, Oosterhof Jan, Nijhuis-van der Sanden MWG. Frequency and location of synkinesis in patients with peripheral facial nerve paresis. Otol Neurotol. 2010;31(4): 671–675.
2.    Moran CJ, Neely JG. Patterns of facial nerve synkinesis. Laryngoscope. 1996;106(12 Pt 1);1491–1496.
3.    Chua CAN, Quhill F, Jones E, et al. Treatment of aberrant facial nerve regeneration with botulinum toxin. Orbit. 2004;23:213–218.
4.    Adour KK, Byl FM, Hilsinger RL, Kahn ZM, Sheldon MI. The true nature of Bell’s palsy: analysis of 1000 consecutive patients. Laryngoscope. 1978;88:787–801.
5.    Manikandan N. Effect of facial neuromuscular re-education on facial symmetry in patients with Bell’s palsy: a randomized controlled trial. Clin Rehabil. 2007;21(4):338–343.
6.    Laskawi R. The use of botulinum toxin in head and face medicine: an interdisciplinary field. Head Face Med. 2008;4:5.
7.    Husseman J, Metha RP. Management of synkinesis. Facial Plast Surg. 2008;24:242–249.
8.    Guerrissi JO. Selective myectomy for post paretic facial synkinesis. Facial Plast Surg. 1991;87:459–466.
9.    Esslen E. Electromyographic findings on two types of misdirection of regenerating axons. EEG Clin Neuro Physiol. 1960;12:738–741.
10.    Ide C, Karo S. Peripheral nerve regeneration. Neurosci Res Suppl. 1990;13:157–164.
11.    May M. Microanatomy and pathophysiology. In: May M, Schaitkin B, eds. The Facial Nerve. New York: Thieme; 2000:57–65.
12.    Yamaoto E, Nishimura H, Hirono Y. Occurrence of sequelae in Bell’s palsy. Acta Otolaryngol Suppl. 1988;446:93–96.
13.    Celik M, Forta H, Vural C. The development of synkinesis after facial nerve paralysis. Eur Neurol. 2000;43:147–151.
14.    Diels JH. New concepts in nonsurgical facial nerve rehabilitation. Adv Otolaryngol Head Neck Surg. 1995;9: 289–315.
15.    Segal B, Hunter T, Danys I, Freedman C, Black M. Minimizing synkinesis during rehabilitation of the paralyzed face: preliminary assessment of a new small-movement therapy. J Otolaryngol. 1995;24:149–153.
16.    Brach JS, VanSwearingen JM, Lenert J, Johnson PC. Facial neuromuscular retraining for oral synkinesis. Plast Reconstr Surg. 1997;99(7):1922–1931.
17.    Beurskens CHG, Devriese PP, van Heiningen I, Oostendorp RAB. The use of mime therapy as a rehabilitation method for patients with facial nerve paresis. Int J Ther Rehab. 2004a;11:206–210.
18.    Beurskens CH, Heymans PG. Mime therapy improve facial symmetry in people with long term facial nerve paresis: a randomized controlled trial. Aust J Physiother. 2006;52: 177–183.
19.    Yanagihara N, Hato N, Murakami S, Honda N. Transmastoid decompression as a treatment of Bell’s palsy. Otolaryngol Head Neck Surg. 2001;124:282–286.
20.    Nakamura K, Toda N, Sakamaki K, Kashima K, Takeda N. Biofeedback rehabilitation for prevention of synkinesis after facial palsy. Otolaryngol Head Neck Surg. 2003;128(4): 539–543.
21.    Ross B, Nedzelski JM, Mclean JA. Efficacy of feedback training in long-standing facial nerve paresis. Laryngoscope. 1991;101:744–750.
22.    Nakamura K, Toda N, Sakamaki K, Kashima K, Takeda N. Biofeedback rehabilitation for prevention of synkinesis after facial palsy. Otolaryngol Head Neck Surg. 2003;128: 539–543.
23.    Borodic G, Bartley M, Slattery W, et al. Botulinum toxin for aberrant facial nerve regeneration: double-blind, placebo-controlled trial using subjective endpoints. Plast Reconstr Surg. 2005;116:36–43.
24.    To EWH, Ahuja AT, Ho WS, et al. A prospective study of the effect of botulinum toxin A on masseteric muscle hypertrophy with ultrasonographic and electromyogrpahic measurement. Br J Plast Surg. 2001;54:197–200.
25.    Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Opthalmol. 1980;87:1044–1049.
26.    Roggenkamper P, Laskawi R, Damenz W, Schroder M, Nussgens Z. Botulinum toxin treatment of synkinesis following facial paralysis. HNO. 1990;38:295–297.
27.    Armstrong MW, Mountain RE, Marray JA. Treatment of facial synkinesis and facial asymmetry with botulinum toxin type A following facial nerve palsy. Clin Otolaryngol Allied Sci. 1996;21:15–20.
28.    Smet-Dieleman H, Van de Heyning PH, Tassignor MJ. Botulinum A toxin injection in patient with facial nerve palsy. Acta Otorhinolaryngol Belg. 1993;47:359–363.
29.    Mountain RE, Murray JA, Quaba A. Management of facial synkinesis with Clostridium botulinum toxic injection. Clin Otolaryngol Allied Sci. 1992;17:223–224.
30.    Roggenkamper P, Kaskawi R, Damenz W, Shroder M, Nussgens Z. Involuntary lid closure caused by defective healing of facial paralysis and its treatment with botulinum toxin. Klin Monatsbl Augenheilkd. 1991:268–270.
31.    Arikan OK, Tan FU, Kendi T, Koc C. Use of botulinum toxin type A for the treatment of masseteric muscle hypertrophy. J Otolaryngol. 2006;35:40–43.
32.    Roggenkamper P, Laskawi R, Damenz W, Schroder M, Nussgens Z. Orbicular synkinesis after facial nerve paralysis: treatment with botulinum toxin. Doc Opthalmol. 1994;86: 395–402.
33.    Ito H, Nakano S, Kusaka H. Low dose subcutaneous injection of botulinum toxin type A for facial synkinesis and hyperlacrimation. Acta Neurol Scan. 2007:115:271–274.
34.    Borodic G, Bartley M, Slattery W, et al. Botulinum toxin for aberrant facial nerve regeneration: double blind, placebo-controlled trial using subjective endpoints. Plast Reconstr Surg. 2005;116:36–43.
35.    Mancini R, Khadavi NM, Goldberg RA. Nonsurgical management of upper eyelid margin asymmetry using hyaluronic acid gel filler. Ophthal Plast Reconstr Surg. 2011;27(1):1–3.

Share on facebook
Facebook
Share on twitter
Twitter
Share on linkedin
LinkedIn