University of Groningen
Facial palsy: treatment, quality of life, and assessment
van Veen, Tijn
DOI:
10.33612/diss.131756313
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2020
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van Veen, T. (2020). Facial palsy: treatment, quality of life, and assessment. University of Groningen.
https://doi.org/10.33612/diss.131756313
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The studies described in this thesis provide insight into treatment effects, quality of life and assessment of facial palsy. In this chapter, the primary findings are listed, discussed and placed in a wider context. Furthermore, implications for future studies and clinical practice are presented.
SMILE REANIMATION SURGERY
The inability to smile is a major disability and in the last 50 years, much progress has been made in smile reanimation surgery. However, room for improvement remains. In part II of this thesis, mainly comparative clinical studies of smile reanimation procedures were performed. In chapter 2.1 we studied cross face nerve grafting (CFNG) procedures and demonstrated
that larger muscles produce more movement, even when neurotised by a similar nerve. In chapter 2.2 we examined if the addition of a CFNG to a hypoglossal-facial jump
anastomosis was of benefit to patients. A higher FaCE scale total score and FaCE scale Social Functioning subscale score was found for patients with the combined procedure (n = 5) compared to those without the CFNG (n = 7), although not statistically significant. In chapter 2.3 the value of dual innervation in gracilis muscle transplantations for
long-standing facial palsy was investigated. We demonstrated that dually innervated gracilis muscles produce more synchronous movement while watching a funny video when compared to nerve-to-masseter driven smile reanimation.
In chapter 2.4 we presented our modification of the temporalis muscle transposition
technique according to Rubin. In chapter 2.5 we then compared the results of temporalis
muscle transposition (n = 12) to gracilis muscle transplantation (n = 10) in adult patients with long-standing facial palsy. No statistically significant differences were found and the absolute values of most outcomes did not differ much.
In chapter 2.6 we looked at the patient’s experience of smile use and procedure-related
morbidity in nerve-to-masseter driven smile reanimation. Amongst other things, we demonstrated that patients generally report good voluntary smiling abilities, and less optimal spontaneous smiling abilities. Generally, patients report acceptable levels of procedure-related morbidity.
Chapter 2.7 is a systematic review and meta-analysis of spontaneity of smile in smile
reanimation procedures. Facial nerve-driven procedures were found to have the highest likelihood of producing a spontaneous smile after surgery, followed by hypoglossal, accessory and masseteric nerve-driven smile reanimation. Moreover, physiotherapy was found to be beneficial with regard to the development of a spontaneous smile.
VI
The major limitation of most studies in this part of the thesis was the sample size of the study population. The total amount of patients included in the study ranged from 12 in chapter 2.2 to 71 patients in chapter 2.6, with smaller numbers per subgroup. Although these sample sizes are not uncommon in the field of facial palsy – the median sample size of the studies included in the meta-analysis of chapter 2.7 was 10 patients – this is a limitation because smaller studies are associated with low statistical power, inflated false discovery rates, inflated effect size estimation, and low reproducibility.1 The question
might arise if these studies are worth doing. I personally do believe so.
Smile reanimation surgery is relatively rare, especially when taking into account that many different surgical techniques are being performed. For example, two of the largest centres in the world report performing approximately 15 gracilis muscle transplantations per year.2,3 Only these few large centres would be able to publish studies with substantial
samples sizes and even then, most likely, either retrospective or cross-sectional, or with years of prospective inclusion. In those years of inclusion new surgical techniques may be developed and existing techniques might be modified within the study cohort. These changes within a cohort hamper comparisons. Additionally, not reporting smaller series of smaller institutions would mean that the literature does not truly reflect the field of smile reanimation as a whole. Since smile reanimation is relatively rare and many subgroups can be identified, meta-analysis can be helpful to answer certain research questions, as we did in chapter 2.7. Reporting smaller (and non-significant) studies is also essential, since this might otherwise introduce reporting bias. Furthermore, smaller series can be hypothesis generating and a way for clinicians with an idea to share their thoughts with the field.
Another limitation in clinical research of smile reanimation is the large set of outcome measures that is available and being used. Because authors use different outcomes, comparison between centres and techniques is hampered, inhibiting advancement of the field. Outcome measures will be discussed in more detail under the heading ‘assessment of facial function’.
Facial movements are complex. Where in the early days of facial reanimation a functioning free flap was seen as the end goal, the field has now moved beyond that point. In recent years, much more tailored and detailed procedures have been described, such as multi-vector free flaps4,5 and segmental innervation,6,7 with the aim of resembling natural facial
movement more closely. In the future, it will be helpful to study the added benefit of these more elaborate procedures. Lastly, many patients with facial palsy will need more than one surgical procedure. Up till now, the effects of these procedures are studied as separate entities, while an approach in which they are studied simultaneously will allow for a better understanding of the effects of the interventions on patients with facial palsy. Future research should study facial reanimation procedures in multivariate models, hence gaining a more accurate view of their effect.
MIME THERAPY AND TREATMENT OF SYNKINESIS
In a Delphi study in 2018, both health professionals and patients determined prevention and treatment strategies for synkinesis to be a top 10 research priority (number 1 according to health professionals, number 4 according to patients).8 In part III the results
of two studies relating to the treatment of synkinesis are described.
In chapter 3.1 a mixed methods study was performed amongst all registered mime
therapists in the Netherlands and Flanders investigating perceptions of and attitudes towards mime therapy itself. In both the interviews with 13 therapists and the questionnaire results of 127 therapists, considerable variation in the therapists’ perceptions and attitudes was found. Latent class analysis revealed two underlying types of therapists: a more ‘positive’ and more ‘negative’ therapist. This difference could potentially influence treatment outcomes.
In chapter 3.2 we studied the long-term results of a two-step highly selective
neurectomies for refractory periocular synkinesis. Long-term measurements of palpebral fissure width were found to be statistically significantly larger compared to preoperative measurements, although palpebral fissure width did decrease in time from the direct postoperative measurement to the long-term measurement.
Synkinesis is a serious condition similar to flaccid facial palsy, as recent health utility studies have demonstrated.9,10 However, treatment of facial synkinesis remains
practice-based to some extent. The majority of patients with synkinesis can be treated with facial rehabilitation therapy,11 chemo denervation,12-14 or a combination of both.14-16 What exactly
is the working mechanism of facial rehabilitation therapy, the ideal chemo denervation treatment schedule (i.e. location and frequency of injections), and if the combination of both treatments results in better outcomes compared to either treatment alone, remains largely unknown.
Surgical treatment of synkinesis is much less often reported, but seems to get more attention amongst facial nerve physicians in recent years.17,18 There are no studies
published comparing surgical and conventional non-surgical treatment. Until evidence supporting the relative benefit of surgical treatment is available, surgery should remain for those not responding to non-invasive treatment. Especially, since the results of the study presented in chapter 3.2 suggest that surgical treatment also does not pose a definitive solution for synkinesis.
Studies investigating optimal treatment protocols would mean a great step forward in the care of patients suffering from synkinesis. More knowledge about the natural course of synkinesis and prediction of treatment success would support the optimization of treatment protocols.
VI
QUALITY OF LIFE
Facial palsy may greatly affect ones psychosocial well-being.19 Although several studies
investigated factors associated with poor quality of life, a comprehensive understanding of facial palsy-related quality of life was missing. Therefore, in part IV we set out to improve the estimation of facial palsy-related quality of life and thereby increasing our understanding of the impact of facial palsy on quality of life.
In chapter 4.1 we performed a cross-sectional study on retrospective data in a cohort
of 920 facial palsy patients of the Massachusetts Eye and Ear Infirmary. FaCE scale total scores were found to be associated with eFace total scores, aetiology, being overweight, anxiety, chronic pain, having received previous treatment, radiotherapy, and the duration of facial palsy. The R2 of the final multivariate model was 0.261, with an R2 was 0.189 for
the univariate regression analysis of eFace total score on FaCE scale total scores (the quality of life measure). This means that only 26.1% of the variance in FaCE scale total scores could be explained, of which 18.9% was explained by the eFace total score. In chapter 4.2 we examined if inclusion of all 15 individual eFace items – instead of the
eFace total score – would increase the explained variance in FaCE scale total scores in the same cohort of 920 facial palsy patients. The cohort was split into ‘flaccid’ (n = 529) and ‘non-flaccid’ (n = 391) facial palsy patients and we found an increase in explained variance in both groups. However, a large difference in explained variance was seen between both groups as well (29.7% and 16.8% for the ‘flaccid’ and ‘non-flaccid’ facial palsy patients respectively). To our surprise, the eFace synkinesis items were of very little importance in ‘non-flaccid’ facial palsy patients. This led us to the hypothesis that clinician-graded and patient-perceived synkinesis are two different constructs, and that the inclusion of the patient perspective into a regression model would allow for better estimation of facial palsy-related quality of life.
In chapter 4.3 we performed a cross-sectional study at the physical therapy clinic of the
same institution and set out to estimate FaCE scale total scores with the eFace total score, some general patient characteristics, and the Synkinesis Assessment Questionnaire (SAQ) total score. We found that the SAQ total score accounted for a relatively large proportion of explained variance (R2 change = 0.113).
The design of the first study in this part of the thesis (chapter 4.1) was rather similar to a previous study20 from the same institution, however, with two great improvements:
eFace scores were available of all patients, meaning that facial function could be included in the multiple regression model. Additionally, the number of investigated potentially associated variables was greatly increased of which many were found to be significantly associated. This meant that the explained variance of the model increased from the previously reported 3.8% to 26.1%. In the follow-up studies (chapters 4.2 and 4.3)
models were established with an explained variance that increased to 42.8%. Although this is a substantial increase, there is still room for improvement.
One of the main limitations of the study presented in chapter 4.1 was its retrospective design. Although eFace and FaCE scale assessments were meticulously gathered, other data such as body mass index and the degree of anxiety was not. Classification of patients as suffering from depression or anxiety was based on medication records. Additionally, the ‘weight status’ of a patient was based on the impression of the first and second author, looking at photographs of the face. This could have led to information bias and increased estimation uncertainty. In a more recent study, the association between psychological factors and personality and facial palsy-specific quality of life was studied.21 The level of
anxiety was measured by using the Hospital Anxiety and Depression Scale (HADS)22 and
found to be significantly associated with facial palsy-specific quality of life. Combining the results of the studies from this thesis and the more recent study in a prospective cohort would be an interesting next step in understanding facial palsy and its impact on quality of life. Another limitation of the studies presented in this part of the thesis is the choice of outcome measure. In all three studies, the FaCE scale total score was used which is a summary measure of the six different domains of the FaCE scale.23 Previous research has
shown that the explained variance of the subdomains differs substantially (ranging from 3.7% to 39.6% explained variance).24 Use of the domain scales may increase knowledge
about facial palsy-related quality of life since the domains may very well be associated with different explaining variables. Similarly, only the FaCE scale was used, while another facial palsy-specific quality of life outcome – the Facial Disability Index (FDI)25 – is also
available. These questionnaires differ to a certain extent and the results could have been slightly different using the FDI instead of the FaCE scale. In the previously mentioned recent study, both the FaCE scale and the FDI were used, and the Sunnybrook Facial Grading System26 was used to measure facial function. As expected the Sunnybrook score
was significantly associated with the FaCE scale total score. However, when looking at the FDI, the Sunnybrook score was significantly associated to the FDI physical function, but not to the FDI social/well-being function.21 The latter may indicate that the severity of facial
palsy is not (linearly) associated to the degree of social disability a patient experiences. The FaCE scale – and FDI – are presented as measures of disease-specific quality of life, but when looking at the content of the questionnaire critically, one could conclude that they are more measures of patient-perceived disability. Although there are associations between disease-specific quality of life and patient-perceived disability, quality of life encompasses more than just disability. Quality of life includes physical, emotional and social well-being, and living a full-filling life in general but also in the context of a specific disease.27 The development of the Face-Q Facial Palsy module seems closer to this
definition and it will be exciting to see if the associations found using the FaCE scale and FDI will hold when using the Face-Q Facial Palsy module.28
VI
Another direction for the future will be the use of more general patient-reported outcome measures (PROMs) in facial palsy. Although they may be too general to measure improvement after treatment for a certain disease, general PROMs do present a more holistic view of how someone is functioning, not only in relation to a certain disease. Although health utility studies in facial palsy have definitely established that (moderate to severe) facial palsy is a severe condition,9,10 it would be interesting to see what the
relative influence of facial palsy is on a more general measurement of quality of life.
ASSESSMENT OF FACIAL PALSY
Reliable and valid assessment of facial function is essential in treating and studying facial palsy. In part V we set out to study aspects of various outcome measures for facial palsy. In chapter 5.1 we examined the learning curve of two inexperienced medical students for
assessing facial function in 100 facial palsy patients using the Sunnybrook Facial Grading System. We found that interobserver agreement between both observers improved over time, and stabilized after approximately 70 assessments at an adequate level.
In chapter 5.2 we developed a three-dimensional assessment of facial asymmetry using
stereophotogrammetry and investigated sources of variation in the outcomes. Reliability of the assessment was good, and variation in the outcome in patients was largely due to the facial expression.
In chapter 5.3 we translated and cross-culturally validated the FDI for use in the
Netherlands. The translated questionnaire demonstrated adequate validity and reliability. Moreover, we determined the smallest detectable change, which was 17 points (on a 100 point scale) at the level of the individual.
In chapter 5.4 we looked at a layperson assessment of aesthetics in smile reanimation
surgery. Thirty-five naïve observers were asked to rate pre- and postoperative photographs of 21 facial palsy patients undergoing either gracilis free functioning muscle transfer or temporalis transposition. We found that the variation in aesthetic scores was predominantly determined by differences between observers and much less by differences between patients. Aesthetic scores did not differ for both smile reanimation procedures, and neither sex nor age of the patient or observer could explain part of the aesthetic scores.
In chapter 5.5 artificial intelligence based emotion detection software was used as a
proxy for layperson assessments of emotional expression. The ‘emotionality quotient’ was developed and defined as the percentage probability of perceived joy over the percentage probability of perceived negative emotions during smiling. In 10 normal subjects 100
percent joy and no negative emotion was detected. Compared to the normal subjects, facial palsy patients showed less joy and more negative emotion. Smile reanimation significantly improved the expression of joy and decreased the expression of negative emotion in facial palsy patients during smile.
In part V a contribution was made towards the assessment of facial palsy in all four domains: (subjective) clinician-based assessment, objective assessment, patient-reported outcomes, and, rather novel, layperson assessment. The fact that assessment of facial palsy consists of four domains already demonstrates the largest difficulty in the assessment of facial palsy: one single measurement of disease severity does not describe the complete picture. A comprehensive assessment thus always includes multiple outcome measures. Additionally, many different measurements exist within a domain. A 2015 systematic review of clinician-based grading systems for facial palsy found 19 scales,29 and since then at least one new scale (the eFace30) has been described. Similarly,
in a 2012 systematic review, 28 questionnaires were found assessing facial palsy.31 The
heterogeneity in outcome measures used makes inter-institutional comparison very difficult, a problem which was also encountered in the chapters described in part II. Gaining consensus throughout the field on which outcomes to use would be very helpful. Recently, one such initiatives has been published: the ICHOMS project standardizing outcome measures in paediatric facial palsy.32 The result is a standard set of outcomes
consisting of 20 outcome domains. Although comprehensive, the extensive nature of the outcome set may hamper its introduction and use within clinical departments. Future research aiming at reducing the outcome set – without losing comprehension – would be of great value and assist adoption in routine clinical practice.
Lastly, validity and reliability of outcomes used in facial palsy have been well-studied. However, the interpretability received insufficient attention. Interpretability is defined as “the degree to which one can assign qualitative meaning – that is, clinical or commonly understood connotations – to an instrument’s qualitative scores or changes in scores”.33
The FaCE scale23, FDI25 and SAQ34 are all regularly used questionnaires – in both research
and clinical practice – but what an absolute score means or when change within an individual patient can be considered meaningful remains largely unknown. This problem was also encountered in chapters 2.2 and 2.4 for example: the differences between both groups were not statistically significant – at least in part because of small sample sizes – but clinical relevance could not easily be evaluated. The same problem holds for measurements of facial function: how many points improvement in Sunnybrook26
or eFace30 scores can be considered meaningful? Studies investigating concepts such
as minimal important change and smallest detectable change would be very usable for clinical practice and are luckily now being set up.
VI
GENERAL REMARKS AND FUTURE PERSPECTIVES
Treating facial palsy is a team effort, and clinicians from multiple disciplines will always be involved. However, facial palsy-related care is in my view currently being delivered in too many medical centres. Since the clinical presentation of the disorder varies so much, large numbers of patients are needed in order to generate large enough subgroups for truly meaningful research and – it is my belief – for building clinical expertise.
On the one hand, increasing cooperation between centres could generate large enough databases for research and the numbers of patients for clinical studies. In our digital era, online – preferably international and open access – databases could rather easily be employed. These databases would not only improve research opportunities, but will also allow treating clinicians to compare individual results to international peers and learn from each other, ultimately also improving direct patient care.
On the other hand, not only working together of centres, but centralising these procedures may hypothetically improve care and simplify research practices. Although the Dutch minister of Health and health care insurance companies currently consider the medical and physiotherapeutic treatment of Bell’s palsy first line treatment, smile reanimation surgery is definitely tertiary care. Specifically for the Netherlands, it is my personal understanding that surgical reconstruction of the facial nerve is performed in almost every University Medical Centre and in some major teaching hospitals. Concentrating on perhaps two or three centres where multidisciplinary facial palsy teams – consisting of an otolaryngologist, plastic surgeon, physical therapist and/or speech and language therapist, neurologist, ophthalmologist, and preferably a psychologist – are present, could increase interdisciplinary cooperation, decrease treatment delay for a patient, and thus ultimately improve patient care. To best make use of such a centralised structure, it is my belief that all facial palsy-related interventions should be performed by these few selected centres so that patient complaints can be identified early, novel treatments fast implemented, teams can generate the patient load needed for enough clinical expertise to qualify as facial palsy ‘experts’, and research data can be gathered easier and more accurate. Centralization would form the basis for the introduction of integrated care in facial palsy. Although no data is available supporting the benefit of integrated care in facial palsy and smile reanimation surgery, evidence of other fields suggests treatment outcomes will improve.35-37 Studies investigating the added benefit of a
multidisciplinary facial palsy team would be highly interesting and provide evidence to move forward in this direction.
CONCLUSION
This thesis provides insight into treatment effects, quality of life and assessment of facial palsy. Throughout this discussion, several directions for future research are described. It is my belief that patient care and clinical research would benefit from centralization of care and scientific cooperation between treatment centres. Only then, can meaningfull progress in the care for patients with facial palsy be made.
RESEARCH PLANS
The before mentioned 2018 Delphi study identified 36 ‘high priority’ research questions for facial palsy according to health professionals and patients in the United Kingdom.8
Personally I feel I am not the person to decide which studies into facial palsy should be performed next. However, I do have some ‘personal favourites’, that I would like to get involved in over the next years:
• What is the relative influence of facial palsy on general quality of life compared some of the most prevalent chronic diseases?
• What shape describes the relationship between facial function and quality of life best? • What are the smallest detectable change and minimal important change of common
measurement instruments used in facial palsy?
• Does the presence of a multidisciplinary facial palsy team lead to better treatment outcomes?
• Does a good patient-therapist relationship lead to better outcomes of facial rehabilitation therapy?
VI
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