Advances and future directions in the care of patients with facial paralysis

Abstract

This article highlights some of the modern-day advancements in facial reanimation surgery including an update on timing of intervention, modifications to free gracilis muscle transfer as well as novel muscle transfers, treatments for synkinesis, minimally invasive procedures, and treatments for ocular paralysis. We also discuss how machine learning and artificial intelligence have been applied to the facial paralysis population with the hopes of developing a standardized, objective assessment tool for evaluating facial function. Although not yet routinely used among facial nerve specialists, advances in bioengineering have been applied to nerve allografts and synthetic conduits, and several experimental studies to enhance neural regeneration are underway. Lastly, we discuss other novel areas of research including neuroprosthetic devices, artificial muscle, use of fluorescent dyes, and the role of acupuncture, which may ultimately change how we manage patients with facial paralysis in the future. This article highlights some of the modern-day advancements in facial reanimation surgery including an update on timing of intervention, modifications to free gracilis muscle transfer as well as novel muscle transfers, treatments for synkinesis, minimally invasive procedures, and treatments for ocular paralysis. We also discuss how machine learning and artificial intelligence have been applied to the facial paralysis population with the hopes of developing a standardized, objective assessment tool for evaluating facial function. Although not yet routinely used among facial nerve specialists, advances in bioengineering have been applied to nerve allografts and synthetic conduits, and several experimental studies to enhance neural regeneration are underway. Lastly, we discuss other novel areas of research including neuroprosthetic devices, artificial muscle, use of fluorescent dyes, and the role of acupuncture, which may ultimately change how we manage patients with facial paralysis in the future. Since the first documented nerve transfer to restore facial nerve function in the late 19th century,1TICKLE TG. SURGERY OF THE SEVENTH NERVEJ Am Med Assoc. 1948; 136: 969https://doi.org/10.1001/jama.1948.02890320013003Google Scholar,2Lee EI, Hurvitz KA, Evans GRD, et al. Cross-facial nerve graft : past and present. 2008:250-256. doi:10.1016/j.bjps.2007.05.016Google Scholar facial nerve surgeons have pushed the boundaries of feasibility in order to restore facial function. Modern surgical practices for both static and dynamic interventions have sought to improve smile reanimation and functional outcomes, reduce the morbidity of autologous nerve grafting, and lessen the burden of synkinesis. Major advancements in modern facial reanimation surgery include early surgical intervention to diminish the detrimental consequences of longstanding muscle denervation as well as innovations to the free gracilis flap, including new innervation techniques, use of multidirectional vectors, and combination procedures, to achieve a more natural smile. Although obtaining objective, quantitative facial analysis in a standardized fashion remains a challenge, several tools utilizing advances in machine learning algorithms and artificial intelligence have been applied to the facial paralysis population. New research evaluating applications of molecular and tissue engineering in the development of artificial nerve grafts and conduits, technological innovations in manufacturing prosthetic and implantable devices, and novel developments to aid visualization of nerves and facial microcirculation may enhance our current understanding of nerve regeneration and potentially be clinically translated in the future. In the setting of facial nerve transection, early tension-free primary repair has been shown to provide the best functional outcomes.3Jandali D Revenaugh PC. Facial reanimation: an update on nerve transfers in facial paralysis.Curr Opin Otolaryngol Head Neck Surg. 2019; 27: 231-236https://doi.org/10.1097/MOO.0000000000000543Google Scholar, 4Spector JG Lee P Peterein J et al.Facial nerve regeneration through autologous nerve grafts.Laryngoscope. 1991; 101: 537???554https://doi.org/10.1288/00005537-199105000-00017Google Scholar, 5Kim J. Neural reanimation advances and new technologies.Facial Plast Surg Clin North Am. 2016; 24: 71-84https://doi.org/10.1016/j.fsc.2015.09.006Google Scholar When this is not feasible, cable graft repair is preferred as long as the proximal facial nerve remains intact and the necessary nerve gap does not exceed limits of the available donor nerve length. Planned facial reanimation is recommended for anticipated facial nerve injury such as during large head and neck oncologic resections and ideally should be performed simultaneously at the time of tumor removal.6Crawford KL Stramiello JA Orosco RK et al.Advances in facial nerve management in the head and neck cancer patient.Curr Opin Otolaryngol Head Neck Surg. 2020; 28: 235-240https://doi.org/10.1097/MOO.0000000000000641Google Scholar If the proximal main trunk of the facial nerve is also damaged or involved with malignancy, nerve transfers involving the masseteric or hypoglossal nerves can reinnervate targeted native facial musculature. For patients with benign skull base tumors facing facial nerve transection and subsequent facial paralysis, concurrent cable graft repair combined with more reliable procedures, such as a masseteric nerve transfer, can improve the chances of restoring smile with 2 mechanisms in case the cable graft repair is unsuccessful (Figure 1). In the setting of unclear anatomic continuity, such as after vestibular schwannoma resection, and postoperative facial palsy, identifying good candidates for early reinnervation has been a challenge. The length of time that it takes for patients with an injured facial nerve to recover also remains unknown; however, this has been shown to be inversely correlated with age.7Verdú E Ceballos D Vilches JJ et al.Influence of aging on peripheral nerve function and regeneration.J Peripher Nerv Syst. 2000; 5: 191-208https://doi.org/10.1046/j.1529-8027.2000.00026.xGoogle Scholar,8Kim L Byrne PJ. Controversies in contemporary facial reanimation.Facial Plast Surg Clin North Am. 2016; https://doi.org/10.1016/j.fsc.2016.03.016Google Scholar Historical management has delayed surgical intervention for at least 1 year to allow adequate time in case spontaneous recovery of facial nerve function does occur. 8Kim L Byrne PJ. Controversies in contemporary facial reanimation.Facial Plast Surg Clin North Am. 2016; https://doi.org/10.1016/j.fsc.2016.03.016Google Scholar,9Boahene K. Reanimating the paralyzed face.F1000Prime Rep. 2013; 5: 1-10https://doi.org/10.12703/P5-49Google Scholar This “watch and wait” approach results in unnecessary delays in the subset of patients that do not recover spontaneously. Moreover, ongoing changes in the motor end plates of denervated facial muscles and progressive muscle atrophy can ultimately result in suboptimal reinnervation and functional outcomes with longer durations of paralysis.10Zhang S Hembd A Ching CW et al.Early masseter to facial nerve transfer may improve smile excursion in facial paralysis.Plast Reconstr Surg - Glob Open. 2018; https://doi.org/10.1097/GOX.0000000000002023Google Scholar,11Dougherty W, Liebman R, Loyo M. Contemporary techniques for nerve transfer in facial reanimation. 2021. doi:10.20517/2347-9264.2020.195Google Scholar In a review of 281 patients with facial paralysis following vestibular schwannoma resection, Rivas et al12Rivas A Boahene KD Bravo HC et al.A model for early prediction of facial nerve recovery after vestibular schwannoma surgery.Otol Neurotol. 2011; 32: 826-833https://doi.org/10.1097/MAO.0b013e31821b0afdGoogle Scholar found that the rate of facial nerve recovery during the first year could independently predict poor functional outcomes in patients with initial House Brackmann grades V to VI as early as 7 months after surgery with 97% sensitivity and specificity. In a follow up study by Albathi et al,13Albathi M Oyer S Ishii LE et al.Early nerve grafting for facial paralysis after cerebellopontine angle tumor resection with preserved facial nerve continuity.JAMA Facial Plast Surg. 2016; 18: 54-60https://doi.org/10.1001/jamafacial.2015.1558Google Scholar patients who were predicted to spontaneously recover were stratified to an observation group and patients who had not recovered any facial nerve function at 6 months were offered either masseteric or hypoglossal nerve transfer. Those who underwent reanimation surgery developed recovery on average 5.6 months after masseteric nerve grafting and 10.8 months after hypoglossal nerve transfer. Those who declined surgery demonstrated at best HB grade V function at mean follow up of 20 months. Intraoperative direct facial nerve stimulation confirmed absence of EMG responses and facial muscle contraction, suggesting there was no additional risk of premature intervention at 6 months post injury.13Albathi M Oyer S Ishii LE et al.Early nerve grafting for facial paralysis after cerebellopontine angle tumor resection with preserved facial nerve continuity.JAMA Facial Plast Surg. 2016; 18: 54-60https://doi.org/10.1001/jamafacial.2015.1558Google Scholar Contemporary facial nerve surgeons now favor earlier intervention if 6 months has passed without clinically discernable recovery. Free muscle transfer has become the gold standard technique for patients with longstanding, irreversible facial palsy (flaccid or synkinetic) or unsatisfactory results from nerve transfer with the gracilis muscle being the most commonly used donor muscle.8Kim L Byrne PJ. Controversies in contemporary facial reanimation.Facial Plast Surg Clin North Am. 2016; https://doi.org/10.1016/j.fsc.2016.03.016Google Scholar Although controversy exists regarding the ideal innervating nerve and staging of procedures, major advancements to free gracilis muscle transfer include multi-vector placement and dual innervation to achieve improved upper lip elevation and dental show while maintaining a spontaneous and robust response.11Dougherty W, Liebman R, Loyo M. Contemporary techniques for nerve transfer in facial reanimation. 2021. doi:10.20517/2347-9264.2020.195Google Scholar,14Boahene KO Owusu J Ishii L et al.The multivector gracilis free functional muscle flap for facial reanimation.JAMA Facial Plast Surg. 2018; https://doi.org/10.1001/jamafacial.2018.0048Google Scholar, 15Kim MJ Kim HB Jeong WS et al.Comparative study of 2 different innervation techniques in facial reanimation: cross-face nerve graft-innervated vs double-innervated free gracilis muscle transfer.Ann Plast Surg. 2020; 84: 188-195https://doi.org/10.1097/SAP.0000000000002034Google Scholar, 16Boonipat T, Robertson CE, Meaike JD, et al. Dual innervation of free gracilis muscle for facial reanimation : What we know so far. 2020:2196-2209. doi:10.1016/j.bjps.2020.05.084Google Scholar A summary of these modifications can be found in Figure 2. Although spontaneous smile outcomes can be achieved with the cross-face nerve graft (CFNG) innervating a gracilis, particularly in younger patients, higher rates of successful smile reanimation outcomes and oral commissure excursion marginally favor the masseteric nerve.17Bhama PK Weinberg JS Lindsay RW et al.Objective outcomes analysis following microvascular gracilis transfer for facial reanimation: A review of 10 years’ experience.JAMA Facial Plast Surg. 2014; 16: 85-92https://doi.org/10.1001/jamafacial.2013.2463Google Scholar, 18Hontanilla B Marre D Cabello Á. Facial reanimation with gracilis muscle transfer neurotized to cross-facial nerve graft vs masseteric nerve: A comparative study using the FACIAL CLIMA evaluating system.Plast Reconstr Surg. 2013; 131: 1241-1252https://doi.org/10.1097/PRS.0b013e31828bd4daGoogle Scholar, 19Vila PM Kallogjeri D Yaeger LH et al.Powering the gracilis for facial reanimation: A systematic review and meta-analysis of outcomes based on donor nerve.JAMA Otolaryngol - Head Neck Surg. 2020; 146: 429-436https://doi.org/10.1001/jamaoto.2020.0065Google Scholar Additional benefits of masseteric innervation include a single-stage gracilis procedure, limited donor site morbidity, faster time to facial nerve recovery (typically 3-6 months), and robust axon supply resulting in powerful muscle contraction.20Klebuc MJA. Facial reanimation using the masseter-to-facial nerve transfer.Plast Reconstr Surg. 2011; 127: 1909-1915https://doi.org/10.1097/PRS.0b013e31820e9138Google Scholar The main disadvantage of using the masseteric nerve is that the smile that evolves is volitional and is not truly spontaneous or emotionally mediated. A high degree of patient motivation and extensive facial neuromuscular training therapy is also typically required in order to achieve satisfactory bite-driven results. Some have argued that spontaneous smile can eventually be achieved in select patients with a bite-activated smile. In a video analysis of 10 patients, Klebuc 20Klebuc MJA. Facial reanimation using the masseter-to-facial nerve transfer.Plast Reconstr Surg. 2011; 127: 1909-1915https://doi.org/10.1097/PRS.0b013e31820e9138Google Scholar reported that 75% developed effortless smile without teeth clenching following gracilis transfer coapted to the masseteric nerve after 2 years. The mechanism behind this is believed to be based on a preexisting neural connection between the facial and trigeminal motor nuclei promoting ease of cortical adaptation after CNV to VII transfer.21Schaverien M Moran G Stewart K et al.Activation of the masseter muscle during normal smile production and the implications for dynamic reanimation surgery for facial paralysis.J Plast Reconstr Aesthetic Surg. 2011; 64: 1585-1589https://doi.org/10.1016/j.bjps.2011.07.012Google Scholar In a prospective study using 30 patients undergoing free gracilis transfer innervated by the masseteric nerve, Lenz et al 22Lenz Y Kiefer J Dietrich F et al.Pre-operative masseter muscle EMG activation during smile predicts synchronicity of smile development in facial palsy patients undergoing reanimation with the masseter nerve : A prospective cohort study.J Plast Reconstr Aesthetic Surg. 2019; 72: 505-512https://doi.org/10.1016/j.bjps.2018.11.011Google Scholar performed preoperative EMG to assess involuntary activation of the masseter muscle upon smiling which they termed co-activation. They found that preoperative masseter co-activation was predictive of smile synchronicity and development of involuntary smile postoperatively with a 99.7% sensitivity and 88.5% specificity.22Lenz Y Kiefer J Dietrich F et al.Pre-operative masseter muscle EMG activation during smile predicts synchronicity of smile development in facial palsy patients undergoing reanimation with the masseter nerve : A prospective cohort study.J Plast Reconstr Aesthetic Surg. 2019; 72: 505-512https://doi.org/10.1016/j.bjps.2018.11.011Google Scholar Functional magnetic resonance imaging (fMRI) to investigate the theory of brain adaptation has been performed in healthy subjects showing distinct cortical areas corresponding to teeth clenching and voluntary smile with minimal overlap; however, alterations in cortical mapping after facial reanimation are still poorly understood and the full potential of human neuroplasticity remain unknown.23Romeo M Vizioli L Breukink M et al.A functional magnetic resonance imaging paradigm to identify distinct cortical areas of facial function: A reliable localizer.Plast Reconstr Surg. 2013; 131: 3-9https://doi.org/10.1097/PRS.0b013e3182818b68Google Scholar Ultimately, the choice of CFNG vs masseteric innervation is highly individualized and discussion with patients regarding the desire for spontaneous smile as well as bite-activated smile outcomes should take place with all candidate facial palsy patients. When a CFNG is selected as the neural source for a free gracilis muscle transfer, it is typically performed in 2 stages spaced out by 6-9 months to allow neural regeneration across the CFNG from the contralateral facial nerve. To reduce the number of facial reanimation surgeries, a simplified single stage CFNG gracilis transfer technique, in which an extended obturator nerve is dissected into the obturator foramen allowing for up to 12cm of nerve to be harvested and tunneled directly across the upper lip to connect to the contralateral facial nerve, was proposed in 2002; however, the 2-staged procedure yielded better symmetry at rest.24Kumar VPA Hassan KM. Cross-face nerve graft with free-muscle transfer for reanimation of the paralyzed face: A comparative study of the single-stage and two-stage procedures.Plast Reconstr Surg. 2002; 109: 451-462https://doi.org/10.1097/00006534-200202000-00006Google Scholar Currently the 2 staged free gracilis transfer innervated by CFNG prevails due to its more reliable reported outcomes. Watanabe et al25Watanabe Y Akizuki T Ozawa T et al.Dual innervation method using one-stage reconstruction with free latissimus dorsi muscle transfer for re-animation of established facial paralysis : simultaneous reinnervation of the ipsilateral masseter motor nerve and the contralateral facial nerve to improve the quality of smile and emotional facial expressions *.Br J Plast Surg. 2009; 62: 1589-1597https://doi.org/10.1016/j.bjps.2008.07.025Google Scholar first reported dual innervation of a latissimus dorsi free flap in 2009. Dual innervation of the gracilis with the masseteric nerve and the contralateral facial nerve via a CFNG was later introduced in 2012 to optimize oral commissure excursion and spontaneity.26Biglioli F Colombo V Tarabbia F et al.Double innervation in free-flap surgery for long-standing facial paralysis.J Plast Reconstr Aesthetic Surg. 2012; 65: 1343-1349https://doi.org/10.1016/j.bjps.2012.04.030Google Scholar Controversy remains, however, regarding the ideal method for nerve coaptation and number of stages. Biglioli et al26Biglioli F Colombo V Tarabbia F et al.Double innervation in free-flap surgery for long-standing facial paralysis.J Plast Reconstr Aesthetic Surg. 2012; 65: 1343-1349https://doi.org/10.1016/j.bjps.2012.04.030Google Scholar implemented a novel 1 stage free gracilis muscle flap dually innervated by the masseteric nerve coapted end to end with the obturator nerve with a CFNG inserting end to side distal to the masseteric neurorrhaphy, closer to the gracilis muscle. Although only 4 patients were included in the study, smile movement was achieved on average 3.8 months postoperatively and spontaneous smile was achieved on average at 7.2 months. EMG electrical assessment was limited due to artifact while attempting to stimulate the masseteric nerve, however gracilis muscle motor units were recorded when the patient smiled without clenching their teeth. Sforza et al27Sforza C Frigerio A Mapelli A et al.Double-powered free gracilis muscle transfer for smile reanimation: A longitudinal optoelectronic study.J Plast Reconstr Aesthetic Surg. 2015; 68: 930-939https://doi.org/10.1016/j.bjps.2015.03.029Google Scholar reported outcomes of 13 patients using an identical dual innervation single staged gracilis muscle transfer and demonstrated an additive effect to smile outcomes when patients clenched their teeth while also smiling through analysis with a 3D optoelectronic motion analyzer. According to a review by Boonipat et al,16Boonipat T, Robertson CE, Meaike JD, et al. Dual innervation of free gracilis muscle for facial reanimation : What we know so far. 2020:2196-2209. doi:10.1016/j.bjps.2020.05.084Google Scholar the majority of dually innervated free gracilis muscle transfers performed by facial nerve specialists are done in a single staged fashion using end to end masseteric and end-to-side CFNG coaptations. Alternate neurorrhaphy patterns for gracilis innervation have also been described such as an end to end coaptation of the CFNG to obturator nerve and end-to-side coaptation of the masseteric nerve by Cardenas-Mejia et al28Cardenas-Mejia A Covarrubias-Ramirez JV Bello-Margolis A et al.Double innervated free functional muscle transfer for facial reanimation.J Plast Surg Hand Surg. 2015; 49: 183-188https://doi.org/10.3109/2000656X.2014.988218Google Scholar in a 2-stage procedure in 9 patients, and a double end to end coaptation of the CFNG to the obturator and a masseteric nerve to the distal stump of the intramuscular motor branch of the gracilis muscle by Uehara et al29Uehara M Shimizu F. The distal stump of the intramuscular motor branch of the obturator nerve is useful for the reconstruction of long-standing facial paralysis using a double-powered free gracilis muscle flap transfer.J Craniofac Surg. 2018; 29: 476-481https://doi.org/10.1097/SCS.0000000000004064Google Scholar in 6 patients (Figure 3). Some experts have also attempted splitting the obturator nerve longitudinally to allow equal end to end inputs from both nerve coaptations.30Baccarani A Starnoni M Zaccaria G et al.Obturator nerve split for gracilis free-flap double reinnervation in facial paralysis.Plast Reconstr Surg - Glob Open. 2019; 7: 1-3https://doi.org/10.1097/GOX.0000000000002106Google Scholar,31Tzafetta K Al-Hassani F Pinto-Lopes R et al.Long-term outcomes of dual innervation in functional muscle transfers for facial palsy.J Plast Reconstr Aesthetic Surg. 2021; https://doi.org/10.1016/j.bjps.2021.03.007Google Scholar Dual innervation with a single stage free gracilis muscle transfer is believed to be equally as effective as the traditional 2-stage CFNG free gracilis transfer with the additional benefit of improved dynamic smile symmetry according to one comparative study.15Kim MJ Kim HB Jeong WS et al.Comparative study of 2 different innervation techniques in facial reanimation: cross-face nerve graft-innervated vs double-innervated free gracilis muscle transfer.Ann Plast Surg. 2020; 84: 188-195https://doi.org/10.1097/SAP.0000000000002034Google Scholar Attempts to achieve a natural smile beyond the simple movement obtained by a single vector facial reanimation surgery have been reported with multi-vector flap design; however, the ideal smile type for the individual remains unclear. A genuine smile (Duchenne smile) consisting of both upper lip and oral commissure elevation with dental display with concurrent palpebral narrowing has been described as a positive display of emotion. A social smile (Mona Lisa smile), in contrast, represents a posed smile characterized by mostly outward contraction of the corners of the mouth by the zygomaticus major muscle with suppressed dental display.32Messinger DS Fogel A Dickson KL. What's in a smile?.Dev Psychol. 1999; 35: 701-708https://doi.org/10.1037/0012-1649.35.3.701Google Scholar A recent study by Helwig et al33Helwig NE Sohre NE Ruprecht MR et al.Dynamic properties of successful smiles.PLoS One. 2017; 12: 1-17https://doi.org/10.1371/journal.pone.0179708Google Scholar found that successful smile was not necessarily perceived as a uniform measure, but rather an intricate balance of mouth angle, smile extent, and dental show in combination with dynamic spatiotemporal timing that was unique to the individual. In a prospective study of 12 patients, Boahene et al14Boahene KO Owusu J Ishii L et al.The multivector gracilis free functional muscle flap for facial reanimation.JAMA Facial Plast Surg. 2018; https://doi.org/10.1001/jamafacial.2018.0048Google Scholar proposed a multi-vector gracilis flap design consisting of 2 muscle paddles oriented independently of one another and inserted along 2 vectors in order to improve multiple dynamic smile display zones during facial reanimation. This technique was not only effective in improving lip excursion in 2 dimensions and oral commissure symmetry, but when inserted close to the lateral orbital region, further improved natural smile outcomes by creating a desirable dynamic periorbital wink characteristic of a Duchenne smile.34Duchenne B.The Mechanism of Human Facial Expression or an Alectro-Physiological Analysis of the Expression of the Emotions. New York: Cambridge University PressGoogle Scholar Future studies intend to implement a third muscle paddle for lower eyelid support in hopes of achieving more consistent periorbital animation.14Boahene KO Owusu J Ishii L et al.The multivector gracilis free functional muscle flap for facial reanimation.JAMA Facial Plast Surg. 2018; https://doi.org/10.1001/jamafacial.2018.0048Google Scholar Tzafetta et al31Tzafetta K Al-Hassani F Pinto-Lopes R et al.Long-term outcomes of dual innervation in functional muscle transfers for facial palsy.J Plast Reconstr Aesthetic Surg. 2021; https://doi.org/10.1016/j.bjps.2021.03.007Google Scholar also investigated the effects of multiple vectors on aesthetic smile restoration by splitting the tendinous portion of the gracilis muscle into 4 strips which were then meticulously arranged in 4 locations: (1) at the oral commissure, (2) one-third the distance along a line between the philtrum and commissure, (3) two-thirds distance along a line between the philtrum and commissure, and (4) 2cm below the oral commissure on the lower lip. Eleven patients were analyzed with Emotrics postoperatively and found to show significant improvements in smile angle, upper lip elevation, oral commissure excursion and commissural height within the first year of follow up. Available treatment for correction of synkinesis has previously focused mostly on facial physical therapy and targeted chemodenervation. Azizzadeh et al35Azizzadeh B, Irvine LE, Diels J, et al. Modified selective neurectomy for the treatment of post-facial paralysis synkinesis. 143 2019. doi:10.1097/PRS.0000000000005590Google Scholar developed a novel surgical reanimation technique termed “modified selective neurectomy” (MSN) whereby 65 patients underwent permanent transection of their distal facial nerve branches causing unwanted movement such as platysma contraction, elevation of the lower lip, and lateral/downward oral commissure displacement. Critical nerve branches responsible for producing natural smile and oral competence (branches to zygomaticus major/minor, levator labii/anguli, depressor labii inferioris muscles) were preserved. On average, 6 nerves were transected, and most patients underwent simultaneous procedures including rhytidectomy, CFNG (offered in preparation for secondary gracilis transfer), rerouting of the transected ipsilateral buccal branch to the zygomatic branch in an end-to-side fashion or rerouting the buccal branch via direct muscle neurotization of the zygomaticus muscle; however, these did not significantly affect overall outcomes in each subgroup analysis. Minimal oral incompetence was reported in 7 patients (11%) lasting from 7 days to 8 months; however, 98% of patients were overall satisfied with the procedure at their last follow-up. Another study on 17 patients undergoing MSN reported significant improvements in nasolabial fold depth at rest, oral commissure position at rest, movement with smile, and increases in dental display; however, exacerbations in dysphagia and dysarthria were reported in up to 40% of patients, and therefore should be emphasized during pre-operative patient counseling.36Miller MQ Hadlock TA. Deep dive into denervation: institutional experience with selective denervation in nonflaccid facial palsy.Facial Plast Surg Aesthetic Med. 2021; 23: 241-247https://doi.org/10.1089/fpsam.2020.0325Google Scholar Hussein et al37Hussain G Manktelow RT Tomat LR. Depressor labii inferioris resection: An effective treatment for marginal mandibular nerve paralysis.Br J Plast Surg. 2004; https://doi.org/10.1016/j.bjps.2004.04.003Google Scholar previously described depressor labii inferioris (DLI) resection of the non-paralyzed, contralateral muscle as a novel, safe, office-based procedure capable of improving smile asymmetry without compromising oral competence or interfering with speech in patients with isolated marginal mandibular nerve or unilateral facial nerve paralysis resulting in lower lip asymmetry. Lindsay et al38Lindsay RW Edwards C Smitson C et al.A systematic algorithm for the management of lower lip asymmetry.Am J Otolaryngol - Head Neck Med Surg. 2011; 32: 1-7https://doi.org/10.1016/j.amjoto.2009.08.011Google Scholar described a retrospective review of 58 patients treated at MEEI Facial Nerve Center who achieved improved smile symmetry and reported high satisfaction rates with contralateral DLI resection performed after a series of 3 botulinum injections spaced 4-6 months apart. In patients with synkinesis, serial injections with botulinum toxin are still preferred for initial therapy; however, trials of local anesthesia injection followed by selective neurectomy and myectomy have also been performed. A symmetric smile has been improved in patients with lower face synkinesis by weakening of the ipsilateral depressor anguli oris (DAO) muscle39Jowett N Malka R Hadlock TA. Effect of weakening of ipsilateral depressor anguli oris on smile symmetry in postparalysis facial palsy.JAMA Facial Plast Surg. 2017; 19: 29-33https://doi.org/10.1001/jamafacial.2016.1115Google Scholar and a 2-stage selective neurectomy around the periocular region under local anesthesia has been described for patients with refractory periocular synkinesis.40Hohman MH Lee LN Hadlock TA. Two-step highly selective neurectomy for refractory periocular synkinesis.Laryngoscope. 2013; 123: 1385-1388https://doi.org/10.1002/lary.23873Google Scholar Transmucosal injection into the buccinator muscle is a newer area of treatment being evaluated in patients experiencing intraoral tightness and synkinesis resulting in backward pulling and displacement of the oral commissure.41Wei LA, Diels J, Lucarelli MJ. Treating buccinator with botulinum toxin in patients with facial synkinesis : A previously overlooked target. 2016;32:138-141. doi:10.1097/IOP.0000000000000449Google Scholar Single-s