Reply: Predictors of Facial Synkinesis Severity

We thank Zhu et al. for reading our article1 and sharing their insights. As they noted, the pathophysiology of synkinesis is not well understood. The 4 prevailing theories—cortical reorganization, disrupted organization of the facial nucleus, polyneuronal innervation, and misrouted axon regeneration—are not supported by high-level evidence.2 As they astutely indicated, decreased axonal regeneration and cortical plasticity with age, microvascular disease with smoking and diabetes, and possible increased susceptibility to nerve compression all align well with known pathomechanisms. Interestingly, 2 of the identified predictors—diabetes and smoking—are modifiable, though the impact of smoking cessation or improved glycemic control on synkinesis symptoms remains uninvestigated. However, large studies on diabetic neuropathy have shown that glycemic control does not reliably confer neuroprotection3 or correlate directly with neuropathy severity, despite being beneficial for many other reasons.4 We thank the authors for their comment regarding the use of photographs instead of videos for eFACE, which was validated using videos only. This is an important consideration, and we appreciate the opportunity to elaborate on our rationale. Our team conducted multiple rounds of testing with many graders using exclusively videos, photographs, or combinations of the two. Ultimately, we found that a combination of photographs and videos yielded the most reliable and granular results and overcame the limitations that we encountered in quality, consistency, and precision. From a quality perspective, although all of our videos were recorded in a professional studio, the very high resolution of the photographs allowed us to detect subtle differences in tone and activation, especially in muscles such as the mentalis, for which fine gradations were often lost on video. Regarding consistency and precision, we aimed to limit the subjectivity of the eFACE that was especially present on certain measures, such as the midface and mentalis. During testing phases, there was low interrater reliability in these measures, especially on video-only assessment. With the addition of photographs captured at the point of maximum effort, which was confirmed by crosschecking the video, we were able to anchor our scoring based on clearly defined components, including symmetry, hypertonicity, and relative orientation of structures. This not only improved our interrater reliability but also allowed graders to clearly explain their rationale. That said, platysma synkinesis was always analyzed using video only, as dynamic animation is necessary to appreciate the hypertonicity and synkinesis, which are often not reliably represented in still images. Regarding the use of the eFACE as a standardized tool for severity evaluation, it is important to emphasize that each study must be designed with a methodology that aligns with clearly defined goals. While patient-reported outcome measures provide valuable insight into patient priorities and treatment planning, they are inherently influenced by individual psychology and variability in perception, making them unsuitable for the specific aim of this study. From a practical perspective, they also could not be collected retrospectively, even if desirable. Our goal was to identify variables associated with synkinesis severity in a reproducible and quantifiable manner. Regarding the downstream effect of these factors on treatment response, it would have to be approached from a different angle, as it would require controlling for severity itself, which would be challenging given the inherent variability and patient-specific nature of synkinesis treatment, and would confound and obscure meaningful associations. Thus, while we believe the eFACE was appropriate for this study, it remains limited in addressing the broader questions that the authors raise—important directions that may well be explored in future research. We sincerely appreciate the insights from Zhu et al. and share the view that more in-depth, collaborative research is essential to identify effective ways to help this underdiagnosed and undertreated patient population. DISCLOSURE The authors have no financial disclosures or conflicts of interest to report.