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Too Much or Too Little?: A Systematic Review of Post-Paretic Synkinesis Treatment Jodi B. Lapidus, MPHS1, Johnny Chuieng-Yi Lu, MD1, Katherine B. Santosa, MD, MS2 and Alison K. Snyder-Warwick, MD1 1Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 2Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI

INTRODUCTION METHODS Facial synkinesis is a potentially life-altering sequela of facial nerve injury. Aberrant regeneration A medical librarian performed a literature search of Embase, Ovid Medline, Scopus, Cochrane of the facial nerve after injury can result in involuntary movements that have a detrimental impact Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and on function and quality of life. clinicaltrials.gov in February 2018 for relevant concept terms. Despite the necessity of effective treatment, there is significant controversy among clinicians Full-text English language articles describing prospective and retrospective cohort studies or about the optimal treatment modality, characteristics of therapy, and how to report treatment randomized controlled trials investigating treatments for synkinesis were eligible for inclusion. outcomes. Reviews, comments, experimental studies, and animal studies were excluded. The goals of this study were to comprehensively summarize and evaluate the quality of the Two authors (JBL and JCYL) independently reviewed articles and extracted data. current synkinesis literature, and to compare the effectiveness of common synkinesis treatment Quality was assessed by the Newcastle-Ottawa scale (cohort studies) and the Cochrane modalities. Collaboration tool (RCTs).

RESULTS

Figure 1. Flow diagram of studies in systematic review. Figure 2. Characteristics of included studies. Figure 3. Description of patients by treatment modality. Figure 4. Interval of post-operative assessment. Figure 5. Length of post-operative follow-up time. Patient Physical Combined Treatment type Author Year Nationality Study Design Primary Outcome Chemodenervation Surgery Total Number number Therapy Therapy Records identified through search Chemodenervation Boroojerdi22 1998 Germany Retrospective 10 Five point scale strategy Chemodenervation Cecini16 2013 Italy Prospective 29 Sunnybrook Facial Grading System Male 67 29 21 132 249 (30%) Chemodenervation Choi19 2013 Korea Prospective 42 Sunnybrook Facial Grading System n = 1240 Gender Chemodenervation Couch15 2014 U.S.A. Retrospective 9 Sunnybrook Facial Grading System Chemodenervation Dall'Angelo17 2014 Italy Retrospective 45 Sunnybrook Facial Grading System Female 190 58 60 265 583 (70%) Records removed after deduplication Chemodenervation Filipo18 2012 Italy Retrospective 41 Sunnybrook Facial Grading System 20 n=673 Chemodenervation Neville 2017 U.K. Prospective 51 Synkinesis Assessment Questionnaire (SAQ) Bell’s palsy 108 60 43 166 377 (48.2%) Chemodenervation Toffolla21 2010 Italy Prospective 30 Sunnybrook Facial Grading System Physical Therapy Brach35 1997 U.S.A. Retrospective 14 Movement of points on lip Surgical Physical Therapy Cronin37 2003 U.S.A. Retrospective 24 May Facial Grading Scale (Tumor Physical Therapy Fujiwara34 2017 Japan Retrospective 37 Sunnybrook Facial Grading System 49 41 13 66 169 (21.6%) Titles and abstracts screened resection, Physical Therapy Kasahara38 2017 Japan Retrospective 12 Revised Sunnybrook Facial Grading System n = 567 Iatrogenic) Physical Therapy Van Swearingen36 2003 U.S.A. Retrospective 66 Sunnybrook Facial Grading System Surgery Bigoli39 2017 Italy Retrospective 18 Modified House-Brackmann score Nonsurgical 17 15 10 53 96 (12.1%) Surgery Guerrissi40 1991 Argentina Retrospective 14 Disappearance of synkinesis Trauma Etiology Surgery Henstrom42 2011 U.S.A. Prospective 24 Facial Clinimetric Evaluation 44 Records excluded for relevance Surgery Hohman 2013 U.S.A. Retrospective 3 Facegram Infectious 41 n=412 Surgery Yoshioka 2015 Japan Retrospective 11 Sunnybrook Facial Grading System (Viral, Ramsay 30 33 11 55 129 (16.5%) 43 Surgery Zhang 2010 China Retrospective 11 (Sunnybrook) Toronto Facial Grading System Hunt) Chemodenervation + PT Azuma23 2012 Japan Prospective 13 Percent Eye Opening

Chemodenervation + PT Mandrini24 2016 Italy Retrospective 27 Sunnybrook Facial Grading System Others (Degenerative, 2 4 1 4 11 (1.4%) Full-text articles reviewed Chemodenervation + PT Maria25 2017 Korea Prospective 142 Sunnybrook Facial Grading System Congenital) n = 155 Records excluded for eligibility criteria Randomized Chemodenervation + PT Monini26 2011 Italy 20 Sunnybrook Facial Grading System n=125 Control Randomized • Involuntary movement disorders such as Chemodenervation + PT Pourmomeny27 2015 Iran 34 Sunnybrook Facial Grading System hemifacial spasm, Orofacial dyskinesia, Control DISCUSSION Involuntary Tics, Huntington's disease, or Chemodenervation + PT Rogers28 2007 U.S.A. Retrospective 8 Sunnybrook Facial Grading System other synkinesis (n=9) • Facial palsy as treatment target/facial Chemodenervation + PT Wei29 2015 U.S.A. Retrospective 42 Sunnybrook Facial Grading System  Currently, there is no gold standard treatment or outcome reporting measure for facial synkinesis as an outcome (n=86) Surgery +/- Chemodenervation Bran30 2014 Netherlands Retrospective 11 Questionnaire, Visual Analog Scale • Ineligible study designs: Single case synkinesis. reports, review articles, editorials, Surgery +/- PT and Chemodenervation Chuang33 2015 Taiwan Retrospective 70 Synkinesis Grading System experimental animal studies (n=30)  Despite the sufficient availability of studies, the high heterogeneity, low quality, and overall Studies included in systematic Facial Grading System Surgery +/- PT and Chemodenervation Terzis32 2012 U.S.A. Retrospective 11 (pediatric) review scientific rigor demonstrated in the current literature does not allow adequate comparisons of Facial Grading System n = 30 Surgery +/- PT and Chemodenervation Terzis31 2012 U.S.A. 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