Assessing anxiety, depression and quality of life in patients with peripheral facial palsy: a systematic review

Objective Peripheral facial palsy (PFP) is predominantly a unilateral disorder of the facial nerve, which can lead to psychological disorders that can result in decreased quality of life. The aim of this systematic review was to assess anxiety, depression and quality of life symptoms associated with PFP. Data sources We searched the Medline, PEDro, CINAHL and Google Scholar databases to conduct this systematic review while following Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. The search was performed by two independent reviewers, and differences between the two reviewers were resolved by consensus. Study Selection The search terms used were derived from the combination of the following MeSH terms: “facial paralysis”, “bell palsy”, “anxiety”, “anxiety disorders”, “depression”, “depressive disorders”, “quality of life” and not MeSH: “facial palsy”, “hemifacial paralysis”, “facial paresis”, “Peripheral Facial Paralysis”, using the combination of different Boolean operators (AND/OR). Data Extraction On November 1st (2019). Data Synthesis In total, 18 cross-sectional articles and two case-control studies were selected. Conclusions The cross-sectional articles showed low methodological quality, while the case-control studies showed acceptable methodological quality. Limited evidence suggests that patients with PFP might have increased levels of anxiety and depressive symptoms. A qualitative analysis also showed limited evidence that quality of life might be diminished in patients with PFP. PROSPERO CRD42020159843.


INTRODUCTION
Peripheral facial palsy (PFP) is predominantly a unilateral disorder of the facial nerve (VII cranial nerve), a mixed nerve with both motor and sensory fibers, whose main function is to control the facial expression muscles. In addition, specifically the chorda tympani is a uniquely sensitive branch that innervates the anterior two-thirds of the tongue (Alonso Navarro et al., 2005;De Diego-Sastre, Prim-Espada & Fernández-García, 2005). However, despite being predominantly a unilateral clinical entity, it has been found that PFP can also be a bilateral disorder (Adour et al., 1978;Stahl & Ferit, 1989).
Peripheral facial palsy has been shown to have several etiologies, which can be classified as (a) idiopathic, commonly referred to as Bell's palsy; (b) infectious, such as Lyme disease, otitis media or even related to herpes virus like the Ramsay Hunt syndrome, which occurs by reactivation of the varicella-zoster virus at the geniculate ganglion; (c) genetic such as Melkersson-Rosenthal syndrome or Albers-Schönberg disease; (d) tumorous; (e) traumatic and (f) post-surgical (Herrero Velázquez et al., 2009;Williams, 2010;Lorch & Teach, 2010).
At the motor level, PFP is related to a loss of essential facial functions, such as blinking, nasal breathing, lip sealing, smiling or speaking (Roob, Fazekas & Hartung, 1999;Lorch & Teach, 2010). Involvement of the musculature around the eyes is a key clinical finding for differentiating PFP from central facial palsy although at the beginning of the course of an incomplete PFP, the closing of the eyes may not be affecte (Beurskens & Heymans, 2004). At the sensory level, PFP is characterized by a diminished sense of taste (Roob, Fazekas & Hartung, 1999;Lorch & Teach, 2010).
Peripheral facial palsy can lead to psychosocial disorders such as depressive symptoms, high anxiety levels and reduced quality of life. Changes in facial symmetry can lead to depressed mood, which has previously been associated with maladaptive behavior and depressive symptoms (Macgregor, 1990;Valente, 2004). The facial expressions of patients with PFP are often perceived negatively by observers, even when the patients are smiling (Ishii et al., 2012). Norris et al. (2019) showed that patients with PFP reported a decline in psychological wellbeing due to their perceived appearance and healthcare experience. Further research is therefore needed to relate the functional disorders of PFP to the possible psychosocial effects that esthetic changes can have on this type of patient. Greater knowledge in this regard could increase the therapeutic efficacy of treatments and the quality of life of patients with PFP.
The main objective of this systematic review was to evaluate the involvement of psychological variables such as anxiety, depressive symptoms and quality of life in patients with PFP.

MATERIALS AND METHODS
The present systematic review study was conducted with the defined protocol and subdivided into four phases based on the standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement ( Fig. 1) (Moher et al., 2009). The protocol of this systematic review was registered in an international register prior to starting the article (PROSPERO, CRD42020159843).

Inclusion criteria
The studies included in this systematic review had to meet the following criteria: (a) cross-sectional, cohort or case-control study with a methodological design; (b) patients with PFP; and (c) evaluating only the following variables: anxiety, depression and quality of life.

Search strategy
The systematic search of the included articles was conducted on the following databases: MEDLINE (from 1950 to November 2019), CINAHL (from 1982 to November 2019), PEDro (from 1950 to November 2019) and Google Scholar carried out in the latter on November 1st, 2019. The search terms used were derived from the combination of the following MeSH terms: "facial paralysis", "bell palsy", "anxiety", "anxiety disorders", "depression", "depressive disorders", "quality of life", and not MeSH: "facial palsy", "hemifacial paralysis", "facial paresis", "Peripheral Facial Paralysis", using the combination of different Boolean operators (AND/OR). We used the study design type (observational studies) as a filter. Two independent reviewers (RLT and FCM) performed the search using the same methodology. Differences between the two reviewers were resolved by consensus.

Selection criteria and data extraction
Two independent reviewers (EZS and ECG) conducted the first evaluation of the studies to assess the relevance (or lack thereof) of the systematic review. The reviewers used the articles' title, abstract and keywords for this initial screening process. If there was no initial consensus or the information provided by the abstract contained insufficient information, the full text was reviewed.
The full text was then reviewed to ensure that the studies met the inclusion criteria. A third reviewer (LSM) measured when there were differences between the evaluators until a consensus was reached. The data were extracted using a structured protocol that ensured that the most relevant information was obtained from each study.

Methodological quality assessment
The methodological quality of the articles included in this review was assessed using the Newcastle-Ottawa modified quality assessment scale (NOS) (Deeks et al., 2003). NOS is an appropriate tool for assessing the quality of case control, cohort and cross-sectional studies and has moderate interexaminer reliability (Hootman et al., 2011). NOS consists of 3 criteria with a minimum of 0 stars and a maximum of 4: participant selection, exposure evaluation, results and comparability. In the total star count, each study is rated as one of the following categories: (1) poor, 0-3 stars; (2) acceptable, 4-5 stars; (3) good, 6-7 stars; and (4) excellent, 8-9 stars. (Wells et al., 2015) For the cross-sectional studies, we employed the modified version proposed by Fingleton et al. (2015) in which (1) 0-1 out of a possible 3 stars is considered poor quality, (2) 2 out of 3 is considered acceptable quality and (3) 3 out of 3 is considered good quality.
Two independent evaluators (EZS and ECG) reviewed and examined the methodological quality of the studies included in the present study, and disagreements were resolved by consensus through the mediation of a third evaluator (FCM). Interevaluator reliability was determined using the kappa (κ) coefficient, where (1) κ > 0.7 indicated a high level of interevaluator agreement, (2) κ = 0.5-0.7 indicated moderate interevaluator agreement, and (3) κ < 0.5 indicated low interevaluator agreement (Cohen, 1960).
For the qualitative analysis of the selected studies, we used an adaptation of the classification criteria proposed by Van Tulder et al. (2003) for randomized clinical trials adapted for cross-sectional observational, cohort and case-control studies. The results were divided into five levels depending on the methodological quality: (1) strong evidence, representing results from multiple studies (at least three studies); (2) moderate evidence, representing results from multiple low-quality studies and/or one high-quality study; (3) limited evidence, one case-control and/or low-quality cohort study and/or at least two cross-sectional studies; and (4) conflicting evidence, inconsistent findings across multiple studies (at least three studies), and (5) No evidence, where there are no studies of any kind for an outcome category.
Two studies (

Results of the methodological quality assessment
Of the 20 articles included in this systematic review, 18 were cross-sectional observational studies, and 2 were case-control studies. The 18 cross-sectional studies showed low methodological quality (with scores of 1 out of 3 stars), while the 2 case-control studies showed acceptable methodological quality (with scores of 6 out of 9 stars). The third evaluator was needed to reach consensus on 2 of the articles. According to the kappa coefficient (κ = 0.736), agreement among the assessors was high. The modified NOS results on the quality of the cross-sectional studies are presented in Table 2, while the results of the quality of the case-control studies are presented in Table 3.

Qualitative analysis
There was limited evidence that anxiety levels are higher in patients with PFP ( , with the Self-reported Anxiety Scale in 1 study (Sun et al., 2015), with the General Health Questionnaire in 1 study (Weir et al., 1995), by open interview in 1 study (Silva et al., 2011) and with the Liebowitz Social Anxiety Scale in 1 study (Worrack et al., 2018).

DISCUSSION
The main objective of this review was to analyze the involvement of psychological variables in PFP. The results showed that anxiety and symptoms compatible with depression can be present in patients with PFP. Quality of life can also be diminished in these patients and is related to the presence of psychological factors. Psychological factors can play a role in patients with PFP for several reasons, one of which is the possible involvement of facial palsy in an individual's self-concept. The functional and motor disorders of the facial region present in these patients significantly affect their perception of their self-image (Cross et al., 2000). This perception of physical attributes and self-image (or self-concept) significantly influences mood and self-esteem (Campbell, Assanand & Di Paula, 2003).
The self-concept of patients with PFP is disrupted, in other words, there is a dissonance between their perceived image (the image altered by the PFP) and their learned self-concept, which has previously been associated with a decrease in self-esteem, the presence of anxiety and the appearance of depressive symptoms (Campbell, Assanand & Di Paula, 2003). Previous studies have shown that patients with facial palsy have an altered visualization of the affected side and that their self-concept is jeopardized, which could be related to the results of this study (Ishii et al., 2011).
Patients with PFP routinely report psychological distress due to the negative implications of PFP in social interactions. Previous studies have indicated that these patients' physical appearance reduces their self-esteem and attractiveness, which, due to social stereotypes, makes them appear less intelligent or confident, leading many people to avoid social relationships with patients with PFP (Ishii et al., 2012). Many patients with PFP are unable to express themselves or recognize facial expressions, which can also have a negative effect on their ability to communicate in their social setting, accentuating their difficulties interacting with others (Korb et al., 2016).
These patients might therefore view social interactions negatively, leading them to limit or avoid completely such interactions, resulting in social isolation, a factor highly related to poorer moods and depressive symptoms (Macgregor, 1990;Ishii et al., 2016). A number of studies have shown an association between greater severity of facial palsy and greater depressive symptoms related to these social aspects (Nellis et al., 2017). Some types of facial palsy such as Bell's palsy have been linked to immune system responses in nerve tissue. Previous research studies have shown increased proinflammatory cytokine levels in patients with this disease, which has been linked as a pathogenetic factor to the origin and maintenance of the disease (Yilmaz et al., 2002). Elevated anxiety and stress levels can also increase inflammatory levels, which in turn can exacerbate symptoms. For example, one study showed a two-way relationship between anxiety levels and Bell's palsy (Tseng et al., 2017).
Lastly, quality of life is related to the subjective perception of health, which includes the relationship between physical and mental health, as well as functionality. Quality of life therefore includes individual satisfaction with the state of health and the emotional response associated with it. Therefore, the aspects mentioned above can have a significant influence on the quality of life of patients with PFP (Taşkapilioğlu & Karli, 2013). Our results show that the quality of life can be diminished in these patients and that their perception is closely linked to the psychological factors mentioned above. These results are similar to those obtained for other clinical entities such as temporomandibular disorders (De Trize et al., 2018) and chronic migraine (Fernández-Concepción & Canuet-Delis, 2003).
From a clinical point of view, the results of the present review emphasize the need to thoroughly assess psychological aspects such as anxiety and depressive symptoms in patients with PFP. The correct management of these factors from a biopsychosocial paradigm can have a major impact on therapeutic success and an increase in the patients' quality of life.

Limitations
There are several limitations to be considered when interpreting the results of this systematic review. Firstly, the main limitation to be considered is the heterogeneity of the sample included in this article. It is very complicated to draw solid conclusions when you include patients with different states, moments and durations of PFP. This limitation is very important to consider because the conclusions are established using the whole of this very heterogeneous sample. The results must therefore be considered with great caution. This fact also makes it impossible to carry out a statistical aggregation. Secondly, probably a greater number of psychological variables would have provided more information and could be considered a limitation. Thirdly, a number of the studies presented a high risk of bias due to their methodological quality or limited sample sizes, which could affect the results. Finally, the low number of articles could also be considered a limitation due to the impossibility of performing a meta-analysis or only because of the difficulty in drawing solid conclusions.

CONCLUSIONS
The results of this systematic review showed that patients with PFP can have increased anxiety levels and depressive symptoms, as well as having a decrease of quality of life. The quality of evidence of all outcome measures was limited. It is therefore that the presence of these psychological variables in patients with PFP should be considered clinically. However, the authors stress the heterogeneity of the sample and therefore the findings should be taken with caution.