assessment of the effect and predictability of cross-face...
TRANSCRIPT
Assessment of the effect and predictability of cross-face-nerve-
grafting in reconstruction of facial nerve paralysis
Tijn van Veen | s1956221
Faculty supervisor: Prof. dr. P.M.N. Werker, Head of department
Department: Plastic and Reconstructive surgery, University Medical Center Groningen
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Samenvatting
Introductie: Een facialis paralyse is een ingrijpende aandoening voor de patiënt, zowel fysiek
als psychosociaal. Een cross-face-nerve-graft (CFNG) is een van de meest gebruikte
technieken voor reanimatie van het gezicht. Afhankelijk van de onderliggende pathologie kan
deze CFNG eventueel gecombineerd worden met een spiertransplantaat of een hersenzenuw-
anastomose. Deze studie is een evaluatie van de nervus facialis reconstructies met behulp van
een CFNG in het UMCG en de Isala Klinieken. Het doel van deze studie was om het effect
van de dynamische reconstructies gebruikmakend van een CFNG vast te stellen.
Methoden: Alle patiënten uit het UMCG en de Isala Klinieken die waren behandeld met een
CFNG, al dan niet in combinatie met een musculus gracilis transplantaat of nervus
hypoglossus-facialis anastomose, of een nervus hypoglossus-facialis anastomose zonder
CFNG werden uitgenodigd om deel te nemen. Het beeldmateriaal werd ingedeeld in drie
meetmomenten: preoperatief, postoperatief (0,5 tot 2,5 jaar na de ingreep) en lange termijn
(meer dan 2,5 jaar na de ingreep). Daarnaast werden de patiënten gevraagd een ‘kwaliteit van
leven’-vragenlijst en een synkinesisvragenlijst in te vullen. Het fotomateriaal werd
geanalyseerd met de FACE-gram software en beoordeeld volgens het systeem van May, de
video’s werden beoordeeld volgens het ‘Terzis’ Grading system’. Daarnaast werd de relatie
tussen de mate van afwijking in het gelaat en kwaliteit van leven, en de toegevoegde waarde
van een CFNG aan een hypoglossus-facialis anastomose onderzocht.
Resultaten: Eenenveertig patiënten uit het UMCG en de Isala Klinieken werden
geïncludeerd. Analyse van het fotomateriaal toonde een toename in excursie en een
verbetering van de symmetrie van de mond in rust en lach. Tevens werd een verbetering
volgens de May classificatie van “slecht” naar “goed” gezien. Analyse van het videomateriaal
toonde geen significante verbetering, maar wel verbetering in mediane scores. Uitgesplitst
naar procedure laat de gracilis transplantatie de meest gunstige resultaten zien. Verder is er
geen verband aangetoond tussen de mate van afwijking in het gelaat en de kwaliteit van leven,
en is er geen verschil aangetoond tussen het wel of niet toevoegen van een CFNG aan een
hypoglossus-facialis anastomose.
Conclusie: Deze studie laat zien dat de reconstructieve facialis ingrepen uitgevoerd in het
UMCG en Isala Klinieken, zorgen voor een betere symmetrie van het gelaat. Daarnaast laat
deze studie zien dat de CFNG in mensen, net als overigens eerder bewezen in diermodellen,
uiteenlopende resultaten heeft, afhankelijk van de spier waar deze op aangesloten wordt.
Daarnaast is er geen verband tussen de mate van afwijking in het gelaat en de kwaliteit van
leven aangetoond, en is er geen toegevoegde waarde van een CFNG aan een hypoglossus-
facialis anastomose geobjectiveerd. Deze informatie kan gebruikt worden om in de toekomst
de toevoeging van een CFNG aan een nervus hypoglossus-facialis anastomose te
heroverwegen.
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Summary
Introduction: Facial nerve paralysis seriously affects a patient, both physically as
psychosocially. A cross-face-nerve-graft (CFNG) is one of the most commonly used
techniques for facial reanimation. Depending on the underlying condition, this CFNG can be
combined with a muscle transplantation or a cranial to facial nerve anastomosis. This study is
an evaluation of the facial nerve reconstructions with a CFNG performed at the UMCG and
Isala Clinics. Aim of this study was to assess the effect of dynamic facial nerve
reconstructions using a CFNG.
Methods: All patients from the UMCG and Isala Clinics treated with a CFNG, possibly in
combination with Gracilis muscle transplantation or hypoglossal-facial nerve anastomosis, or
a hypoglossal-facial nerve anastomosis without a CFNG were invited to participate. The
imagery was divided in three categories: preoperatively, postoperatively (0.5 to 2.5 years after
the procedure) and long term (more than 2.5 years after the procedure). Patients were asked to
fill in a quality-of-life and synkinesis questionnaire. The photographs were analyzed with the
FACE-gram software and graded according to May. The videos were graded according to
Terzis’ Grading system. Additionally, a relationship between the degree of facial
disfigurement and quality-of-life, and the additional benefit of a CFNG to a hypoglossal-facial
nerve anastomosis were tested.
Results: Forty-one patients from the UMCG and Isala Clinics were included. Analysis of the
photographs showed an increase in excursion and an improvement of symmetry of the mouth
in repose and during smile. At the same time, an improvement of May classification scores
from “poor” to “good” were seen. Analysis of the video material showed no significant
improvement, although increasing median scores were seen. Divided by type of operation, the
Gracilis muscle transplantation showed the best results. Furthermore, no association between
the degree of facial disfigurement and quality-of-life was seen, and no difference between the
either or not addition of a CFNG to a hypoglossal-facial nerve anastomosis was seen.
Conclusion: This study shows that the reconstructive facial nerve procedures performed,
cause better symmetry of the face. Additionally it shows that a CFNG, as proven in animal
models before, has differing results, depending on the muscle it is attached to. No association
between the degree of facial disfigurement and quality-of-life has, and no additional value of
a CFNG to a hypoglossal-facial nerve anastomosis have been proven. This information can be
used to reconsider the addition of a CFNG to a hypoglossal-facial nerve anastomosis in the
future.
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Table of contents
Introduction 6
Etiology of facial paralysis 6
Clinical signs 6
Natural course and prognosis 7
Facial nerve grading systems 8
Treatment options 8
Aim of this study 11
Research question 11
Primary research question 11
Secondary research questions 11
Patients and methods 12
Patients 12
Power analysis 12
Data collection 12
Outcome measures 16
Statistical analysis 16
Results 18
Inclusion and patient characteristics 18
Reliability testing 18
Primary outcome assessment 19
Secondary outcomes assessment 23
Discussion 25
The effect of dynamic facial nerve reconstructions using a CFNG 25
Association between the degree of facial disfigurement and disease specific QoL 26
Benefit of a CFNG as an adjunct to a hypoglossal-facial nerve anastomosis 27
General limitations, clinical relevance and implications 28
Acknowledgements 30
References 31
Appendix I
Appendix II
Appendix III
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Abbreviations
CFNG - Cross-face nerve graft
FaCE - Facial Clinimetric Evaluation scale
HSV-1 - Herpes Simplex Virus-1
ICC - Intraclass correlation coefficient
IQR - Interquartile range
QoL - Quality of Life
SAQ - Synkinesis Assessment Questionnaire
UMCG - University Medical Center Groningen
VAS - Visual analogue scale
XII-VII - Hypoglossal-facial
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1 Introduction
The facial nerve is of major importance to each individual. It innervates all mimic muscles
and as such controls eye closure, nasal breathing, speech and oral continence (1,2). Next to
these functional aspects facial expression is of importance as it is critical in interpersonal
communication (3). Facial paralysis therefore may seriously affect patients both functionally
and psychosocially.
1.1 Etiology of facial paralysis
Facial paralysis can arise from a broad variety of conditions. These can be grouped in
developmental and acquired. The latter includes infectious, neurologic, neoplastic, traumatic
and systemic causes (4). The most common cause of facial paralysis is unknown and named
Bell’s palsy. The incidence of Bell’s palsy in the Netherlands is 20/100 000/year (5). Bell’s
palsy is a diagnosis of exclusion and is given in approximately 50% of facial paralysis cases
(6,7). Recently, Bell’s palsy has been linked to herpes simplex virus I (HSV-1). Whether
HSV-1 is the definitive causing factor remains unsure until more research demonstrating a
definitive correlation between active replicating HSV-1 and Bell’s palsy is done (4,8).
After Bell’s palsy, developmental and infectious cases are common etiologies of facial
paralysis (9). Perinatal trauma is a very common cause in children (7). A study by the
Massachusetts Eye and Ear Infirmary Facial Nerve Center demonstrated acoustic neuroma as
the second most common cause in their patient population (10).
Table 1. Causes of facial paralysis
Infectious Varicella-zoster-virus (Ramsey-Hunt syndrome)
Otitis media (acuta, suppurative, malignant,
chronic, and with effusion)
Acute mastoiditis
Lyme
HIV
Tuberculosis
Mumps virus
Rubella virus
Influenza virus
Infectious mononucleosis Idiopathic
Bell's palsy
Neurologic Guillain- Barré
Multiple sclerosis
Millard-Gubler syndrome Developmental
Syndromic, e.g. Möbius syndrome
Dystrophic myotonia
Neoplastic Cholesteatoma
Vestibular schwannoma (acoustic neuroma)
Facial neuroma
Carcinoma
Glomus jugularis
Histiocytosis
Rhabdomyosarcoma
Osteopetrosis
Hemangioblastoma
Leukemia Trauma
Iatrogenic
Penetrating wound to face/neck
Birth trauma
Temporal bone fracture
Systemic Sarcoidosis
Diabetes mellitus
Hyperthyroidism
Autoimmune disease
Adapted from ’Melvin and Limb, 2008’ and ‘Ciorba et al., 2015’ (4,7).
1.2 Clinical signs
A disorder in the function of the facial nerve can cause paralysis in all facial muscles.
Depending on the specific site of damage to the nerve, patients will experience certain
complaints. Incomplete eye closure, with the resulting drying out and subsequent irritation of
the cornea and loss of sight, nasal passage obstruction, and difficulties with speaking and
swallowing are common functional problems (1,2). Depending on the cause of paralysis and
personal anatomy, the nervus intermedius can also be affected in facial paralysis. This nerve
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carries parasympathetic fibres and is typically a component of the facial nerve. The nerve has
a role in lacrimation, salivation, taste, hearing, and carries sensory nerves for part of the skin
of the ear (11,12).
Furthermore, the social function of the face, as alluded to earlier, may not be underestimated.
The face is the first point of recognition and is of major importance in interpersonal
communication (13). Loss of facial expression will cause a loss of the ability to express ones
emotions. Research has shown that this has a major impact on psychological wellbeing
(14,15). Facial disfigurement after head and neck surgery has been associated with high rates
of suicide and depression (14,15). The smile seems to be of extra importance. The inability to
smile alone, can lead to an increase in depression symptoms (13,16).
Several studies have been performed in order to establish whether the degree of facial
disfigurement is of influence on the patients’ quality of life (QoL). They found that the degree
of facial disfigurement does not have an effect on QoL, which is in line with the findings in
clinical practice. These studies however, did not use disease specific QoL questionnaires or
were not performed in facial palsy patients but patients with other facial disfigurements (17-
20).
1.3 Natural course and prognosis
Depending on the underlying condition, recovery of the facial paralysis may occur. In Bell’s
palsy up to 70-90% of the patients will experience recovery of facial nerve function (7,9).
With other causes, the prognosis is much less fortunate. The process of nerve regeneration is
not without complications. One of the major complications is synkinesis. The incidence of
postparalysis synkinesis is reported to be up to and even more than 50% (21). Synkinesis can
not only occur with natural recovery of facial paralysis, but also after surgical treatment of
facial paralysis. The postoperative rate of synkinesis is reported to be even higher. Fifty-one
percent of all patients presents with postoperative synkinesis, the majority of whom with a
mild to moderate form (22).
Figure 1. Three mechanisms of synkinesis. (From: Crumley R.L. Mechanisms of synkinesis. Laryngoscope 1979 Nov;89(11):1847-1854. (26))
Synkinesis is the unintentional movement of a portion of the face when voluntarily moving
another part of the face (23). The most common form is oral-ocular synkinesis (24). This is an
unintentional movement of the mouth when blinking or closing the eye, or unintentional eye
closure during talking or smiling. When an axon is cut, Wallerian or anterograde degeneration
occurs in the distal part and degeneration of the proximal part occurs until the first node of
Ranvier (25). The axon and myelin sheath disappear, the Schwann cells and endoneurium
persist in an empty state awaiting the arrival of a regenerating axon. Between the first and
third week, the proximal part of the axon will begin regenerating. At the end of the axon,
A B C
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small axon buds will form that grow distally in search for an endoneural tube (26). Each axon
however, can grow into any multiple vacant endoneural tubes. This will result in the
innervation of nonnative muscle groups. This theory of aberrant regeneration is the most
widely accepted mechanism of synkinesis (Figure 1A) (27).
A second suggested mechanism of synkinesis development results from the loss of the myelin
sheath. After regeneration, the resulting uninsolated axons will stimulate each other, and thus
create synkinesis. As a third and last mechanism, some literature offers evidence of facial
nuclear hyperexcitability as a cause for synkinesis (Figure 1B and 1C) (23).
1.4 Facial nerve grading systems
Although the need for a uniform facial grading system has long been recognized, the gold
standard has yet to be determined (28,29). Several grading systems have been developed and
used in order to clinically assess facial nerve function. Historically the House-Brackmann
scale and Sunnybrook scale are most widely used (30,31). These scoring systems rely on an
assessment by a clinician. The biggest problem with these methods is its low reliability and
the fact that they do not detect small changes in recovery of facial nerve palsy (32). Recently,
(semi-)automated tools have been developed by different facial nerve centers in order to get a
more objective way of scoring these patients. Even three-dimensional measurement systems
have been proposed, taking into account that the face moves in three dimensions (33,34).
Lastly, self-assessment questionnaires are being used more and more. The Facial Clinimetric
Evaluation (FaCE) scale and Synkinesis Assessment Questionnaire (SAQ) have been
validated for use in the Netherlands (35,36). Currently, one can say consensus exists over the
idea that one tool is not enough in order to adequately evaluate the course or treatment of
facial paralysis. A full evaluation should include objective measurements, subjective grading
by a clinician, and a patient self-assessment (37).
1.5 Treatment options
The treatment of facial paralysis is complex and difficult. Multiple surgical and non-surgical
options are available, depending on several patient factors and wishes and the opinion of the
surgeon. The surgical options can be divided in dynamic and static procedures (6). Dynamic
procedures aim to restore facial movement, while static procedures are done to reach resting
symmetry. Generally, dynamic and static techniques are combined whenever possible in order
to get the best result (38).
1.5.1 Non-surgical treatment options
Many patients require some form of protection in the acute phase, especially for the eye. This
is to prevent the eye from drying out and possible complications. It is generally achieved by
using cellulose drops during the day and an ointment containing petrolatum, mineral oil or
lanolin alcohol during the night (39). An hourglass bandage to keep the eye moist and the
application of plaster to lift the corner of the mouth and lateral corner of the eye, to prevent
drooling and protect the cornea respectively, are older applications (40).
The role of specialized physiotherapy in the treatment of peripheral facial nerve paralysis is
not undoubted (41). Biofeedback training with a mirror alone or the addition of EMG
feedback, and exercise therapy however, have been proven to be effective (42).
Mime therapy was developed in the Netherlands by Jan Bronk, mime actor, and Pieter
Devriese, otolaryngologist, in the early 1980’s. Mime therapy consists of automassage,
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breathing and relaxation exercises in order to relax the face, and certain specific exercises for
emotional expression and control synkinesis (43). Mime therapy has proven to decrease
resting asymmetry and synkinetic movement, and to increase symmetry during voluntary
movement in people with long standing facial nerve paralysis (44).
1.5.2 Surgical procedures
1.5.2.1 Static procedures
Static procedures for the treatment of facial nerve paralysis provide both cosmetic and
functional benefits. They are especially suitable for older or otherwise debilitated patients
since the procedures are generally less extensive than dynamic procedures. They can also be
used as an addition to dynamic procedures (38). Examples of static procedures are:
musculature plication or shortening, fascial sling suspension, injectables and implants, brow
lifting, facelifts, eyelid weight surgery, and upper and lower eyelid procedures, lip procedures,
and nasal valve lateralization (39,45).
1.5.2.2 Dynamic procedures
One of the most important initial assessments one should make in facial paralysis is whether
or not the paralysis is reversible. Reversible facial muscles will have intact muscle fibers and
motor units. These muscles can still respond to nerve grafting. After the muscles become
atrophic they will not respond to nerve grafting alone and additional measures will have to be
taken (46). Whether the facial muscles are still viable can be detected by electromyography.
The time to atrophy of the mimetic musculature varies, but is generally complete after 18-24
months (47,48). Dynamic reanimation can be divided accordingly in procedures for recent
facial paralysis and for long standing facial paralysis.
In traumatic or surgical transection, immediate reconstruction must be considered. Primary
end-to-end anastomosis of the facial nerve stump usually gives the best result (46). The
anastomosis should be under no tension in order to be most effective. When the gap is too
large for a direct neurorrhaphy, an interposition nerve graft can be used. The greater auricular
nerve and sural nerve are commonly used for this purpose (49). Naturally, reconstruction
using the ipsilateral facial nerve is of preference. When it is not available there are several
other options of which the most important are: the contralateral facial nerve, hypoglossal to
facial nerve transposition, and most recently the masseteric to facial nerve transposition (46).
In cross-face nerve grafting, the contralateral facial nerve is chosen as a nerve source for the
paralyzed side. One or multiple branches of the healthy side of the face are transected and
connected to the paralyzed side with usually a sural nerve graft (50). Cross-face-nerve-grafts
(CFNG) are believed to be of special importance to reconstruct emotional expression and
protection of the eye, because they may restore a spontaneous smile and blinking of the eye
(47). The results however, were disappointing with patients showing minimal facial
movement (50). CFNG's have been used in the treatment of synkinesis with better results. In
this procedure, the synkinetic branches of the facial nerve are selected, transected and
connected to the distal end of a CFNG. This will result in an appropriate stimulus for the
selected nerve (51-53).
The hypoglossal nerve has long been used as a substitute and is now the most popular motor
source in recent facial paralysis, when the proximal stump of the facial nerve is not available.
The similarities between the facial and hypoglossal nerve in fascicular anatomy and mimetic
and prandial function make it especially suitable (54). Different techniques for a hypoglossal-
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facial nerve anastomosis exist. The original procedure involved fully transecting the
hypoglossal nerve and an end-to-end anastomosis with the facial nerve. Complications are
hemiglossal atrophy and associated problems with speech and swallowing, and synkinesis
(55,56). Modified techniques include a jump graft or rerouting of the intratemporally released
facial nerve and a side-to-end anastomosis (Figure 2). These procedures all offer sufficient
resting tone and a strong source for voluntary movement of the face when moving the tongue.
The hypoglossal-facial nerve anastomosis can be combined with a CFNG in an attempt to
restore a spontaneous smile or blinking of the eye (57).
The masseteric nerve has long been used as a motor source in patients with bilateral paralysis
because of Moebius syndrome (47). It is now growing in popularity for the treatment of
unilateral facial paralysis due to its low donor site morbidity and the strength of the motor
impulse (58).
Figure 2. Techniques of hypoglossal-facial nerve anastomosis. A) the classic end-to-end hypoglossal-facial
nerve anastomosis, B) the hypoglossal-facial nerve jump anastomosis and C) the rerouting technique.
(From: Le Clerc N, Herman P, Kania R, Tran H, Altabaa K, Tran Ba Huy P, et al. Comparison of 3 procedures
for hypoglossal-facial anastomosis. Otol Neurotol 2013 Oct;34(8):1483-1488. (56))
In longstanding facial paralysis the musculature is irreversibly atrophied and a muscle
transposition or transplantation will be necessary in order to regain any movement in the
paralyzed side of the face. Since the inability to close the eyes can ultimately lead to blindness
and smiling is of major importance in psychosocial wellbeing, most procedures will seek to
restore these functions (48).
The temporalis muscle is the most commonly used muscle for transposition. Many
modifications exist, but generally a part of the muscle is detached, and with or without fascial
extension sutured just medially from the nasolabial fold. This technique is favorable over
other muscle transpositions, e.g. masseter muscle transposition, because of its vector of pull
and the almost immediate result. Besides cosmetic disadvantages, the temporalis transposition
also has a limited degree of excursion and no spontaneity (59,60).
Free muscle transplantation is usually performed in a two-stage procedure in order to get
spontaneous movement. The first stage consists of a CFNG, the second involves
microneurovascular transfer of muscle, the gracilis muscle being most common and gold
standard for dynamic reconstruction of the oral commissure (38,61). The gracilis muscle is
especially suitable because of its reliable pedicle anatomy, adequate strength, minimal donor-
site morbidity, and the advantage of a two-team approach. The gracilis is placed in the cheek,
connected to the CFNG and connected to the zygomatic arch and the medial border of the
lips. This creates the preferred lateral-upward vector for a smile (62).
A B C
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1.6 Aim of this study
Several small retrospective studies have been performed to assess the outcomes of dynamic
facial reanimation procedures in both adults and children (61,63-66). A combined study of the
CFNG in all its indications for use has not been done before. This study will be an evaluation
of dynamic reconstructions using a CFNG and the hypoglossal-facial nerve anastomoses with
or without CFNG’s, which has not been done before in our region.
Furthermore, a relationship between the experienced QoL and the degree of facial
disfigurement has not been discovered. However, this has not been studied in facial palsy
patients using in a disease specific QoL instrument (19,20). This study will assess whether
there is such an association.
Lastly, the addition of a CFNG to a hypoglossal-facial nerve anastomosis is believed to be of
great value since a CFNG is the only theoretical source of emotional, i.e. spontaneous,
expression of the face (57). The morbidity of combining the two procedures however is much
higher. We will seek to measure this benefit.
2 Research question
2.1 Primary research question
What is the effect of the dynamic reconstructions using a CFNG, within its indications for
use, or hypoglossal-facial nerve anastomosis?
2.2 Secondary research questions
Does an association between disease specific QoL and the degree of facial disfigurement exist
in facial palsy patients after dynamic reconstruction?
Is the addition of a CFNG to an hypoglossal-facial nerve anastomosis of extra value?
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3 Patients and methods
This study was performed in the University Medical Center Groningen (UMCG) and Isala
Clinics. Since this study concerns evaluation of standard care formal permission from the
institutional review board of both institutions was not necessary. However, exemption was
obtained prior to this study and patients gave their written consent to participate in this study.
3.1 Patients
All patients that underwent a CFNG within one of its indications for use in the UMCG from
September 2006 to November 2015 or the Isala Clinics from January 1999 to August 2006
were initially identified and included in the study. Three indications for a CFNG are currently
used in the UMCG: a CFNG in combination with a hypoglossal-facial nerve (or recently a
masseteric-facial nerve) anastomosis in facial paralysis for less than 18 months, a CFNG with
gracilis free flap in facial paralysis existing for more than 18 months, and a CFNG in the
treatment of synkinesis. Patients with reversible paralysis also received solitary hypoglossal-
facial anastomoses in the past in the UMCG or Isala Clinics. These patients were also invited
to participate in order to assess the additional effect of the CFNG to the hypoglossal-facial
nerve anastomosis. Patients were selected through a medical record search, using operation
codes for CFNG, hypoglossal-facial nerve anastomosis, transposition of a nerve, and free
muscle transplantation to identify the patient group. Additionally, personal records of the
acting surgeon were used to complete the patient group.
Patients that met the following inclusion criterion were selected for this study: the patient had
undergone one of the earlier described operations within the set timeframe. Patients were only
excluded from the study if not enough data was present to include them in one of the analyses
performed. This means that only people that met the following two criteria were excluded:
they did not fill out the FaCE scale questionnaire and did not have a recent video taken, or not
at least one set of pre- and one set of postoperative or long term imagery was present. Because
the patient group was expected to be quite small, inclusion and exclusion criteria were set
relatively wide in order to be able to perform the analyses on as many patients possible.
3.2 Power analysis
It was not possible to perform an a priori sample size calculation. As said, several small
retrospective studies have been performed, however not with a patient population comparable
to ours. Besides, due to the rarity of the treatment studied, an a priori sample size calculation
would not really have been of use since the required sample size would definitely be larger
than the amount of participants that would be possible to acquire in this region. An a
posteriori power analysis is of limited value and would face the same problem: the treatment
studied is so rare that larger numbers of participants or a high level of power would not be
possible (67). This is most certainly a disadvantage of this study, however we feel it is not a
reason not to perform this study.
3.3 Data collection
Demographic variables and pre-, intra- and postoperative data were collected from the
medical history chart and operation report (Table 2). An anonymous database was created for
this study wherein all data were collected. Additionally three questionnaires were send to the
patients. The first is a self-made questionnaire. It consists of additional questions regarding
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their smile, mime therapy, and patients were asked to give a VAS-score regarding the
cosmetic outcome of the surgery. Since some patients underwent supplementary operations in
other hospitals, we also asked some questions regarding the complete state of their medical
history and treatment (Appendix I). The second and third questionnaires were the Dutch
version of the “Facial Clinimetric Evaluation (FaCE) Scale” (Appendix II) and the Dutch
version of the “Synkinesis Assessment Questionnaire (SAQ)” (Appendix III) that have
recently been translated and validated for use in the Netherlands (35,36). Since the
questionnaires have been validated for use in children of 14 years or older, children under the
age of 14 were asked to fill in the questionnaire with the help of a parent (68,69).
During a visit to the UMCG this questionnaire was gone through to see if there were any
missing data. Afterwards a standard set of pictures was taken and a short video was made by
the medical photographer. These photographs and the video were used to analyze the mouth
in repose and with smile. The photographs were analyzed with the FACE-gram software and
graded according to the May classification, the video was analyzed by four independent
observers according to the Terzis’ Functional and Aesthetic Grading System for Smile (70-
72).
Some patients were prepared to fill out the questionnaire, but lived too far away from our
center for a visit to the UMCG. These patients were given strict instructions how they could
take a set of two pictures (in repose and with smile) and a short video.
Photographs and videos taken from 0.5 years up to 2.5 years after the definitive animation
restoring operation (connection of the CFNG to the affected side, date of hypoglossal-facial
nerve anastomosis, or date of implantation of free gracilis muscle) were defined as
‘postoperative’. Imagery taken after 2.5 years was defined as ‘long term’. ‘Recent’
photographs or videos were defined as taken a maximum of six months prior to filling out the
FaCE scale questionnaire.
Table 2. List of variables
Demographic variables Smile analysis variables
Age
Gender
Level of education
Cause of facial paralysis
Side of facial paralysis
Date of onset
Operative variables
Type of operation
Date of operation
Time since operation
Time to reanimation
Additional variables
Mime therapy/time of
mime therapy
Aesthetic VAS score
Total SAQ score
Excursion (length with smile – length in repose)
Healthy and affected side, pre- and postoperative
Δ angle (angle with smile – angle in repose)
Healthy and affected side, pre- and postoperative
Symmetry (length healthy side – length affected side)
Pre- and postoperative
Terzis’ grading score:
Pre- and postoperative
QoL variables
Total FaCE score
Facial Movement Score
Facial Comfort Score
Oral Function Score
Eye Comfort Score
Lacrimal Control Score
Social Function Score
3.3.1 Facial Clinimetric Evaluation Scale
The FaCE Scale was developed in 2001 and is a patient-graded QoL instrument (68). It
consists of 15 items representing all QoL issues affected by facial disability. Patients can
score each item from 1 to 5. A total score and six subscores (Facial Movement Score, Facial
Comfort Score, Oral Function Score, Eye Comfort Score, Lacrimal Control Score and Social
Function Score) can be calculated (Appendix II). The scores can range from 0 (low QoL
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score) to 100 (high QoL score). Recently, the FaCE Scale was translated and validated for use
in Dutch speaking patients. The smallest detectable change of the FaCE Scale is not reported
and it was not possible to calculate it with the data provided in the validation article (35).
3.3.2 Synkinesis Assessment Questionnaire
The SAQ was developed in 2007 and is a simple, reliable and valid instrument for the self-
assessment of synkinesis in facial palsy patients (69). The SAQ is a nine-item questionnaire
on which patients can score 1 to 5 on each item. According to a specific calculation
(Appendix III) the Total Synkinesis Score can be calculated which ranges from 20 (low or no
synkinesis) to 100 (high or a lot of synkinesis). The questionnaire was recently translated and
validated for use in The Netherlands (36).
3.3.3 FACE-gram software
The FACE-gram software developed in the Facial Nerve Center of the Massachusetts Eye and
Ear Infirmary in Boston in 2012 was used to analyze and compare the pre- and postoperative,
and the long term pictures (71). The FACE-gram software scales every photograph according
to the size of the iris (approximately 11.8 mm). After the operator outlines the iris, the
software places a horizontal line from eye to eye and a perpendicular line bisecting the
horizontal line. The operator markes the intersection of the perpendicular line with the
vermillion border of the lower lip (point A). The user then selects the oral commissure (point
B) and with this the software is able to calculate the distance from point A to point B and the
angle of the pull vector (figure 3). The difference in length and angle between repose and
smile is named ‘excursion’ and ‘Δ angle’ respectively. The symmetry is calculated by taking
the difference in length and angle
between the healthy and affected side, a
perfect symmetrical face will hence score
0 (Table 2) (61). The measurement error
for oral commissure excursion with
smiling is 3.5 mm. After dynamic
reconstruction an increase in excursion
of 1-1.5 cm is expected however, thus
the FACE-gram software should be able
to identify significant changes despite the
measurement error (71).
Essential when using the FACE-gram
software is a correct position of the head
in relation to the camera. A minor
rotation in the plane of the camera will
give false measurements because the
software uses 2D, instead of 3D,
material. When the degree of rotation
was deemed too large, the photographs
were not analyzed. This was the case
when the perpendicular line did not run
over the nasal bridge.
Figure 3. Use of the FACE-gram software.
15
3.3.4 May classification
Subjective clinician-based grading was performed according to the May classification (Figure
4) (72). Depending on symmetry of the mouth in repose and during smile the observer rated
the photographs from ‘poor’ to ‘excellent’. Grading was performed by the principal
investigator twice within three days.
Figure 4. May classification for reanimation of the mouth.
(From: May M, Drucker C. Temporalis muscle for facial reanimation. A 13-year experience with 224
procedures. Arch Otolaryngol Head Neck Surg 1993 Apr;119(4):378-82;discussion 383-4. (72))
3.3.5 Terzis’ Functional and Aesthetic Grading System for Smile
To analyze the video material the Terzis’ Grading System (Table 3) was used (70). This is a
reliable observer based scoring system, developed in 1997. Four independent observers were
asked to rate the patients from ‘excellent’ to ‘poor’ according to symmetry and contraction of
their smile. The independent observers were three medical students and a student of
‘Technical medicine’.
Table 3. Terzis’ Functional and Aesthetic Grading System for Smile
Grade Description Score
Excellent Symmetrical smile with teeth showing, full
contraction
V
Good Symmetry, nearly full contraction IV
Moderate Moderate symmetry, moderate contraction,
mass movement
III
Fair No symmetry, bulk, minimal contraction II
Poor Deformity, no contraction I
16
3.4 Outcome measures
The primary aim of this study was to determine the effect of the dynamic reconstructions
using a CFNG. In this case we determined effect by an increase in: commissure excursion,
increase in angle of the commissure, an increase in symmetry in repose or with smile, an
increase in May classification score, or an increase in Terzis’ grading score.
Since many data were missing, we decided to use the May classification score as the outcome
measure for the additional research questions. This was the outcome parameter with the most
data present.
3.5 Statistical analysis
Statistical analyses were performed using IBM Statistical Package for the Social Sciences
(SPSS) version 22, Chicago, IL.
3.5.1 Descriptive statistics
Descriptives of nominal data were given using frequencies and percentages. Ordinal data were
presented using medians and interquartile ranges (IQR), interval data were given using means
and standard deviations. In case of non-normality, interval data were given using the median
and the IQR.
3.5.2 Reliability statistics
Reliability of the scoring according to May and the Terzis’ Grading score was tested.
Intrarater variability for the May scores was tested by calculating the weighted Cohen’s kappa
(κ). Since we calculated the interobserver agreement of four instead of two observers, the
intraclass correlation coefficient (ICC) was chosen as measure for agreement. It was
calculated by putting a latent variable underneath the ordinal Terzis score. An multinomial
mixed model was applied, with a random effect for participant. Based on the variance
components for the random effect, the ICC was calculated using this formula:
A κ or ICC of 0.80 or higher will be considered excellent, a κ or ICC of 0.60 to 0.80 will be
considered substantial (73).
3.5.3 Testing statistics
The primary research question was to determine what the effect is of the dynamic
reconstructions of facial nerve palsy using a CFNG. The Friedman test was used to compare
the preoperative, postoperative and long term length excursion and angle of the commissure,
the symmetry in repose and with smile, the video material scored according to Terzis’ grading
system, and the May scores. Wilcoxon Signed Ranks tests were performed as post hoc tests to
compare between pre- and postoperative, preoperative and long term, and postoperative and
long term results. Mann Whitney U tests will be performed to assess whether a difference can
17
be measured in postoperative outcomes between the different surgical procedures. Only those
outcomes that showed improvement in the first analysis will be assessed.
As post hoc test were performed, one could argue some form of p-value adjustment should be
completed in order to decrease the risk of a type I error. The Bonferroni correction is the most
popular adjustment method, however it is also considered very strict and therefore some
statisticians argue it should not be used. We chose not to perform a Bonferroni correction. The
principle reason is that the tests that we performed are not undirected. We suspect that the
findings are in line with the literature and therefore feel that the chance of a type I error is
already at an acceptable level (74-76).
To ascertain if there is an association between the degree of facial disfigurement and disease
specific QoL, a linear regression analysis was performed with the Total FaCE Score as the
dependent variable and the recent May classification score as independent variable. Amount
of mime therapy and the SAQ score were added as possible confounders.
Lastly, to reveal whether the CFNG is of additional value to a hypoglossal-facial nerve
anastomosis Mann Whitney U tests were performed to compare Total FaCE Score, the Terzis’
grading score and May scores between groups.
18
4 Results
4.1 Inclusion and patient characteristics
Sixty-five patients that underwent one of the described procedures were selected and invited
to participate in the study. Thirty-two patients were willing to participate, of an additional
nine patients at least one set of usable preoperative and postoperative imagery was available.
After exclusion, 41 patients were included in the study. Most patients were excluded because
of a lack of pre- and postoperative imagery.
Table 4. Patient and clinical characteristics
Gender (N (%))
Male 16 (39.0)
Female 25 (61.0)
Age, years ( Median (IQR)) 28.0 (15.8-57.0)
Side of paralysis (N (%))
Left 21 (51.2)
Right 20 (48.8)
Cause of facial paralysis (N (%))
Developmental 11 (26.8)
Vestibular schwannoma resection 10 (24.4)
Bell’s palsy 5 (12.2)
Other 15 (36.6)
Time to reanimation, years (median (IQR)) 5.8 (3.0-9.7)
Time of postoperative follow up, years (median (IQR)) 1.3 (0.9-1.6)
Time of long term follow up, years (median (IQR)) 8.2 (5.0-10.5)
Type of operation (N(%))
Free gracilis transplantation 21 (51.2)
XII-VII anastomosis 7 (17.1)
XII-VII anastomosis + CFNG 6 (14.6)
V-VII anastomosis + CFNG 1 (2.4)
CFNG 6 (14.6)
Most patients presented with developmental facial paralysis (n=11, 26.8%). Second and third
most common were facial paralysis after vestibular schwannoma resection (n=10, 24.4%) and
Bell’s palsy (n=5, 12.2%). Among the other causes of facial paralysis, the removal of a
neoplasm other than a vestibular schwannoma was the most common. Free gracilis
transplantation was the procedure performed most often (n=21, 51.2%). The overall median
age was 28.0 years with an IQR from 15.8 to 57.0 years. The age differed amongst the
different operations: 18.5 years (IQR: 13.5-28.9) for the free gracilis, 58.2 years (46.6-72.2)
for the hypoglossal-facial nerve anastomosis, 53.6 years (41.4-61.4) for the hypoglossal-facial
nerve anastomosis with CFNG, and 36.8 years (22.3-51.8) for the CFNG. The median time
elapsed to the reanimation procedure was 5.8 years, with an IQR from 3.0 to 9.7 years. The
median time of postoperative follow up was 1.3 years after the reanimating procedure. The
median time of long term follow up was 8.2 years after reanimation (Table 4).
4.2 Reliability testing
Intrarater variability for the May classification scores was evaluated by calculating a weighted
Cohen’s kappa. The intrarater variability was excellent with a κ of 0.89.
To test the interrater reliability an ICC was calculated for the Terzis’ Grading score. The
interrater agreement was considered substantial with an ICC of 0.73.
19
4.3 Primary outcome assessment
The Friedman test did not show a statistical significant difference in any of the objective
primary outcome measures: excursion on the healthy and affected side, and symmetry in
repose and with smile (Table 5). The Wilcoxon Signed Ranks test showed a statistical
significant difference between the preoperative and long term excursion on the affected side
(p = 0.004), the pre- and postoperative symmetry in repose (p = 0.005), pre- and postoperative
symmetry with smile (p <0.001), and preoperative and long term symmetry with smile (p =
0.001).
For our subjective primary outcome measures, the Friedman test showed a statistically
significant difference for the May classification scores (p <0.001). Although the median
Terzis’ Grading score increased from the preoperative to postoperative to the long term
measurements, we were not able to perform a Friedman test due to missing data. Of only one
patient all three videos were available. The Wilcoxon Signed Ranks test showed a statistical
significant difference between the preoperative and postoperative (p <0.001) and the
preoperative and long term (p <0.001) May classification scores. The Wilcoxon Signed Ranks
test did not show any statistical significant differences in the Terzis’ Grading score between
pre-, postoperative and long term video’s (Table 5).
20
Table 5. Primary outcome assessment
Outcome
Median (IQR) p-value (N)
e
Friedman test
Wilcoxon Signed Ranks test
Preoperative Postoperative Long term Preoperative
– Postoperative
Preoperative
– Long term
Postoperative
– Long term
Excursion (mm)a
Healthy side 7.6 (4.5-9.9) 6.5 (3.8-8.6) 5.1 (3.4-8.6) 0.150 (14) 0.340 (26) 0.053 (20) 0.782 (17)
Affected side -0.6 (-2.0-2.7) 1.9 (0.4-4.0) 3.5 (1.3-6.3) 0.551 (14) 0.157 (26) 0.004 (20)
0.678 (17)
Δ Angleb
Healthy side 6.6 (1.7-10.1) 5.0 (0.7-7.9) 5.7 (-0.4-11.0) 0.150 (14) 0.847 (26) 0.277 (20) 0.782 (17)
Affected side -0.6 (-6.4-3.5) -1.7 (-4.9-5.2) 1.7 (-1.1-5.9) 0.242 (14) 0.803 (26) 0.841 (20) 0.145 (17)
Symmetry (length, mm)c
Repose 2.0 (-1.6-4.2) -0.5 (-4.7-2.2) -2.3 (-4.6-3.4) 0.369 (15) 0.005 (27)
0.050 (21) 0.424 (17)
Smile 8.8 (4.2-13.3) 2.5 (-0.1-4.9) 2.4 (-5.2-4.7) 0.189 (15) <0.001 (27)
0.001 (20)
0.580 (18)
Symmetry (angle)d
Repose 5.5 (3.0-9.1) 5.0 (0.9-8.7) 4.6 (0.7-9.5) 0.330 (15) 0.269 (27)
0.243 (21) 0.818 (17)
Smile 11.8 (6.5-14.9) 9.3 (4.3-13.0) 7.5 (2.2-12.5) 0.982 (15) 0.111 (27)
0.220 (20)
0.289 (18)
May classification score 1.0 (1.0-2.0) 3.0 (2.0-3.5) 3.0 (2.5-3.9) <0.001 (16)
<0.001 (28)
<0.001 (21)
0.078 (18)
Terzis’ Grading score 1.5 (1.1-2.1) 2.0 (1.5-2.5) 2.5 (2.0-3.5) -b
(1) 0.125 (10) 0.500 (3) 0.563 (7) a Excursion: difference between the distance from the lower lip to the corner of the mouth in repose and during smile.
b Δ Angle: difference between the angle of the corner of the mouth with the perpendicular line in repose and during smile.
c Symmetry (length, mm): difference between the distance from the lower lip to the corner of the mouth on the healthy side and affected side.
d Symmetry (angle): difference between the angle of the corner of the mouth with the perpendicular line on the healthy side and affected side.
e Level of significance: p < 0,05.
f Friedman test could not be computed because not enough valid cases were available.
21
4.3.1 Comparison of primary outcomes between reconstruction methods
Outcomes after Gracilis muscle transplantation connected to a CFNG were generally better
than outcomes of the other procedures. After Gracilis muscle transplantation connected to a
CFNG, patients presented with a larger excursion on the affected side, better symmetry and
higher May classification scores (figure 5). Mann Whitney U tests were performed to assess
whether a statistically significant difference exists. Excursion on the affected side, symmetry
with smile and the May classification scores were assessed. Six Mann Whitney U tests were
statistically significant, p-values of the significant tests are given in table 6.
Table 6. Comparison of outcomes per type of operation.
Outcome p-valuea
Excursion on the affected side
Free Gracilis vs n. XII-VII anastomosis 0.028
Free Gracilis vs CFNG 0.015
Symmetry with smile (length)
Free Gracilis vs n. XII-VII anastomosis 0.046
May classification scores
Free Gracilis vs n. XII-VII anastomosis 0.008
Free Gracilis vs n. XII-VII anastomosis + CFNG 0.047
Free Gracilis vs CFNG 0.006 a Level of significance: p < 0,05.
22
Figure 5. Comparison of primary outcomes per type of operation at the recent moment of time. Bars
represent the IQR.
-2
-1
0
1
2
3
4
5
6
7
8
Free Gracilis n. XII-VII
anastomosis
n. XII-VII
anstomosis +
CFNG
CFNG
Excu
rsio
n a
ffec
ted
sid
e
-8
-6
-4
-2
0
2
4
6
8
10
Free Gracilis n. XII-VII
anastomosis
n. XII-VII
anastomosis +
CFNG
CFNG
Sym
met
ry w
ith
sm
ile
0
0,5
1
1,5
2
2,5
3
3,5
4
4,5
Free Gracilis n. XII-VII
anastomosis
n. XII-VII
anastomosis +
CFNG
CFNG
May c
lass
icif
ati
on
sco
res
23
4.4 Secondary outcomes assessment
4.4.1 Association between degree of facial disfigurement and disease specific QoL
Regression analysis was performed with the recent May score as independent variable and the
Total FaCE score as dependent variable. The amount of mime therapy received and the Total
SAQ score were added as possible confounders. Regression analysis showed no significant
association between the recent May score and Total FaCE score (p = 0.353). The amount of
mime therapy received and Total SAQ score were statistically significantly associated with
the Total FaCE score (Table 7).
Table 7. Regression analysis
Independent variable B SE B β p-value
May score 2.74 2.89 0.15 0.353
Mime therapy in months -0.74 0.20 -0.57 0.001
Total SAQ score -0.76 0.25 -0.46 0.007
4.4.2 Benefit of a CFNG with a hypoglossal-facial nerve anastomosis
Seven patients were treated with a hypoglossal-facial nerve anastomosis alone, and six
patients were treated with a hypoglossal-facial nerve anastomosis with CFNG. Descriptive
statistics were not completely similar for both groups. The hypoglossal-facial nerve
anastomosis without a CFNG group consisted of more women and more right sided paralysis
in comparison to the group of patients treated with a hypoglossal-facial nerve anastomosis
with a CFNG. Another difference was seen in follow up time. The median follow up time in
the group without a CFNG was 6.5 years, compared to 2.4 years in the group with a CFNG.
The median denervation time was comparable in both groups (12.6 and 12.4 months
respectively) (Table 8).
Table 8. Descriptive statistics of XII-VII anastomosis patients with and without CFNG
XII-VII anastomosis
(N = 7)
XII-VII anastomosis +
CFNG (N = 6)
Gender (N (%))
Male 4 (57.1) 5 (83.3)
Female 3 (42.9) 1 (16.7)
Age, years (median (IQR)) 57.9 (46.4-71.9) 53.3 (41.0-61.0)
Side of paralysis (N (%))
Left 4 (57.1) 2 (33.3)
Right 3 (42.9) 4 (66.7)
Cause of facial paralysis (N (%))
Vestibular schwannoma resection 4 (57.1) 4 (66.7)
Developmental 0 (0) 0 (0)
Other 3 (42.9) 2 (33.3)
Denervation time, months 12.6 (11.8-23.3) 12.4 (8.1-26.5)
Time of follow up, years (median (IQR)) 6.5 (1.3-15.1) 2.4 (1.2-6.0)
The Total FaCE score in patients with a hypoglossal-facial nerve anastomosis with CFNG
(median = 68.3) did not differ significantly (p = 0.145) from patients with a hypoglossal-facial
nerve anastomosis (median = 50.0). Not one of the FaCE subscores differed significantly
between both groups (Table 9). Furthermore, the median May score of patients with a
hypoglossal-facial nerve anastomosis with CFNG (median = 2.5) was not statistically
significantly higher than the May score of patients with a hypoglossal-facial nerve
anastomosis without a CFNG (median = 2.0). Terzis’ Grading scores of patients with a
24
hypoglossal-facial nerve anastomosis with CFNG (median = 1.4) did not differ from that of
patients with a hypoglossal-facial nerve anastomosis without a CFNG (median = 2.0).
Spontaneous movement on the affected side during smile was noted in four of the patients that
were treated with a CFNG. Spontaneous movement during smile was noted in one patient that
did not receive a CFNG.
Table 9. Recent outcomes of XII-VII anastomosis with and without CFNG
Median (IQR)
XII-VII anastomosis XII-VII anastomosis
+ CFNG p-value
Total FaCE score 50.0 (40.0-65.0) 68.3 (42.1-71.7) 0.145
Facial Movement score 33.3 (8.3-41.7) 29.2 (22.9-33.3) 0.832
Facial Comfort score 75.0 (41.7-83.3) 83.8 (54.2-100.0) 0.416
Oral Function score 50.0 (25.0-62.5) 68.8 (37.5-90.6) 0.508
Eye Comfort score 37.5 (0.0-62.5) 31.3 (0.0-90.6) 0.818
Lacrimal Control score 100.0 (25.0-100.0) 87.5 (50.0-100.0) 0.980
Social Function score 56.3 (43.8-93.8) 87.5 (48.4-95.3) 0.511
May score 2.0 (2.0-3.0) 2.5 (1.8-3.3) 0.666
Terzis’ Grading score 2.0 (1.5-2.1) 1.4 (1.2-2.3) 0.374
Spontaneous smile 1.000
Yes 1 4
No 4 2
No video available 2 0
25
5 Discussion
The main goal of this study was to perform an evaluation of care of the dynamic facial nerve
reconstructions using a CFNG in our region. Two additional research questions came up:
whether or not the degree of facial disfigurement would be of influence on the QoL, and if the
addition of a CFNG is of value with a hypoglossal-facial anastomosis. For this purpose, the
pre-, intra-, postoperative and long term data of 41 patients were analyzed.
5.1 The effect of dynamic facial nerve reconstructions using a CFNG
The outcome assessment was performed on both video and photo material. The Friedman test
for the May classification score showed a significant increase, the Friedman test for the
Terzis’ Grading score could not be performed because of missing data and all other Friedman
tests were not statistically significant. The Ranks tests were only significant for the
preoperative and long term excursion on the affected side (p = 0.004), the pre- and
postoperative symmetry in repose (p = 0.005), pre- and postoperative symmetry with smile (p
<0.001), preoperative and long term symmetry with smile (p = 0.001), the pre- and
postoperative May classification score (p <0.001), and the preoperative and long term May
classification score (p <0.001).
The May classification score was defined as the most important primary outcome measure,
since most data were present of this outcome. This showed a significant increase from “poor”
preoperatively to “good” postoperatively and long term. We were also very interested in the
Terzis’ Grading score, since we felt the result of dynamic reconstructions could perhaps best
be assessed with a video. The median Terzis’ Grading scores were 1.5, 2.0 and 2.5, at the
preoperative, postoperative and long term time interval respectively. Although we were not
able to perform a Friedman test and the Wilcoxon Signed Ranks tests showed no statistically
significant difference, we do see a distinct increase in Terzis’ Grading score indicating an
improvement in smile and facial symmetry. Our results are in line with earlier published data,
although slightly disappointing. In 1997 already, Terzis and Noah studied the postoperative
results of a group of combined procedures. In this article they show a statistically significant
increase from a mean of 1.6 to a mean of 3.0 (70). Terzis and Olivares published two articles
demonstrating a statistically significant increase in the Terzis’ Grading score in children and
adults two years after facial reanimation with a free muscle transplant from a mean of a little
over 1.0 to a mean of around 3.0. They also showed a continued statistically significant
increase in Terzis’ Grading score in the long term evaluation to a mean Terzis’ Grading score
over 3.0 (64,65). Our data do show an increase in Terzis’ Grading score and a continued
increase in the long term evaluation, although not significant and not reaching the scores
reported in the literature.
A cross-sectional outcome analysis of recent measurements of the most relevant primary
outcome parameters showed a significantly better result with Gracilis muscle transplantation
compared to the other procedures with a CFNG. At first glance, this difference is strange,
taking into account that the CFNG is connected to the same branch of the healthy facial nerve
in all three procedures, so one would expect the same behavior of the CFNG. A CFNG
however is a peculiar thing. In several animal model studies it was established that the
eventual result in cross-face nerve grafting not only depends on which motor source is
selected, but also on the target muscle (77,78). Besides, in animal models, the facial nerve is
able to control muscles up to three times the size of the original (79). This study shows that
the same phenomenon takes place in humans, where the implanted Gracilis muscle is much
larger than the original facial muscles and causes a larger excursion on the same CFNG
26
compared to a connection of the CFNG to an original facial nerve branch on the affected side
(as with an addition to hypoglossal-facial nerve grafting or a solitary CFNG). The different
median ages amongst the different groups of patients have to be taken into account however,
since the younger a patient is, the better the expected result is. The fact that the postoperative
result with Gracilis muscle transplantation is better than with the other procedures, could thus
be partially caused by the younger group of patients.
One of the main disadvantages of this study was the low quality the pictures since most of
them had at least a minor head rotation in them. We still analyzed them because of two
reasons: we feel a full evaluation of facial reanimation surgery should include both objective
and subjective scoring, as supported by the literature (37,80), and we wanted to see how these
minor head rotations would influence the measurements. One could argue that when the
sample size is large enough, all these minor rotations will equal each other out. This will still
make these measurements unsuitable for comparison between centers or patients, but this
would give an idea of the effect of the operation as a whole. Four of the Wilcoxon Signed
Ranks tests performed in the analysis of the pictures were statistically significant. Since we
included images with minor head rotation the fact whether a change is statistically significant
however is of less importance. What we do see when looking at the means is the desired and
expected change: an increase in excursion on the affected side, an increase in angle difference
on the affected side, and symmetry measures closer to 0 (Table 5). Although we cannot
compare our exact measurements to other studies, we do see the same trend as reported
elsewhere (61,63).
Another disadvantage was the fact that the interrater agreement for the Terzis’ Grading score
was only substantial. This could be caused by the fact that the videos were not taken with the
idea to use them for grading according to Terzis. This system focuses on a smile, and the
videos present in the UMCG include the patient speaking, and at the very end, a quick smile.
Perhaps, that was the reason the observers found it difficult to score the patients, and hence
they did not agree.
As said, this is the first evaluation of care in this region. Although this study contains many
limitations, it is of value in the sense that it gives an idea of what the effect is of the
operations done. A full evaluation however would consist of objective analysis, subjective
scoring, and a patient self-reported outcome measure. One of the limitations of this study is
that it was not possible to perform this full evaluation. Not only were many data missing, the
minor head rotations made objective analysis impossible. Hadlock and Urban reported this
problem already when validating the FACE-gram software. They decided to add padded sides
to the head rest to ensure the perpendicularity of the camera to the facial plane (71).
Unfortunately, this issue was not recognized in this region before. Very recently, facial
reanimation surgery has proven to statistically significantly increase patient self-reported QoL
(81). Patient self-assessments have not been done in either the UMCG or Isala Clinics
however, thus performing such an analysis in this region was impossible. For future
evaluation and research, standardized, all-round reporting would be desirable. Based on the
data at hand, we do can say that our procedures are of value.
5.2 Association between the degree of facial disfigurement and disease specific QoL
We did not find an association between the QoL and the degree of facial disfigurement. We
did however find a statistically significant relationship between the QoL and both the amount
of mime therapy received and the total SAQ score.
27
The finding that there is no relationship between QoL and facial disfigurement is not
surprising. Although this exact relationship has not been studied before, multiple studies have
been performed either studying this relationship in a population with facial disfigurement
other than facial paralysis or using a QoL instrument not especially designed for facial
paralysis patients (14,18,20,82).
To our knowledge, the finding that both the amount of mime therapy and the Total SAQ score
are negatively related to the QoL has not been reported before. Our reasoning behind using
the amount of mime therapy as a confounder was that we expected mime therapy to have a
positive influence on both QoL and the degree of facial disfigurement. Mime therapy is
proven to be of value in improving facial function and symmetry in facial paralysis (44). We
also reasoned that the psychological aspect of mime therapy, including patient information
and coping strategies (43), could have a positive influence on QoL, not regarding the physical
result of the therapy. We found a negative association however, meaning that the longer one
was treated by a mime therapist, the lower they rated their QoL. Most patients received mime
therapy on their own initiative. This could mean that only patients that either perceive more
problems or feel as if they need guidance in controlling their facial paralysis see a mime
therapist. In this sense a negative relation between the amount of mime therapy and QoL can
very well be understood.
One of the limitations of this study was that even according to the most liberal calculation of
the amount of variables allowed in a linear regression analysis, we used too many (76). We
still chose to perform the linear regression this way because we felt both confounders were of
equal importance. Although this is the first study reporting an investigation of the degree of
facial disfigurement and disease specific QoL for facial paralysis patients after dynamic
reconstruction, the test should be repeated with a larger sample size for a definitive statement.
The result that we found though, is in no way pointing in the direction that such a relationship
should exist.
5.3 Benefit of a CFNG as an adjunct to a hypoglossal-facial nerve anastomosis
In order to assess the added benefit of a CFNG we measured QoL, the May classification
score, the Terzis’ Grading score, and the presence of a spontaneous smile. Mann Whitney U
tests did not show any statistically significant difference for any of the outcome parameters
between the groups of hypoglossal-facial nerve anastomosis patients with and without a
CFNG.
The addition of a CFNG to a hypoglossal-facial nerve anastomosis is believed to be of
importance since a CFNG is theoretically the only source of spontaneous, i.e. emotional,
movement (57). Emotional movement is of great influence on one’s psychological wellbeing,
and the ability to smile is of special importance (13,16). Therefore we expected to see a
difference in Total FaCE score between the two groups. To our knowledge, no literature has
been published on this subject however. Different medians were calculated for both groups, a
median of 50.0 (IQR 40.0-65.0) and 68.3 (IQR 42.1-71.7) for a hypoglossal-facial nerve
anastomosis without and with CFNG respectively. This difference was not statistically
significant. Besides not being statistically significant, Kleiss et al. did not report the smallest
detectable change of the Dutch FaCE scale. This mean that the difference of 18.3 points could
possibly be in the error range.
In an attempt to measure a difference in overall outcome between the two groups we took the
May classification score and Terzis’ Grading score as outcome measures. These did not differ
28
between the group of patients with a CFNG and the group of patients without a CFNG, with
medians of 2.5 and 2.0, and 1.4 and 2.0 respectively.
Lastly, we did assess if a spontaneous smile was present. We did find a spontaneous smile in
four of the six patients treated with a CFNG. We also found one spontaneous smile in the
group of patients without a CFNG. Spontaneity however, is a difficult and controversial term
in facial reanimation surgery. The importance of the difference between spontaneity and
automatism has been addressed in the literature (83). Some believe that only a true emotional
spontaneous smile will be of benefit to the patient, and not an automatic smile. The one
spontaneous smile we found in the group of patients without a CFNG could very well be an
automatic smile instead of an emotional smile.
A limitation in this study is the skew distribution of the descriptive statistics. Although we
have no reason to assume that the gender or side of paralysis is of influence on one of the
outcome measures, the time of follow up could very well be. As was demonstrated earlier, we
see an improvement, continuing after two years. The short follow up time in the group
patients with a CFNG (median = 2.4) compared to the follow up time in the group of patients
without a CFNG (median = 7.0), could very well cause an underestimation of the results of
the first group. This would mean that the non-significantly difference we found now, could
become significantly different over time.
Furthermore, one could argue that the addition of a CFNG to a hypoglossal-facial nerve
anastomosis should lead to spontaneous movement, and we did not have a research setup in
which we could test true spontaneity. Spontaneous movement is believed to be of importance
however because of its influence on psychological wellbeing. We did measure QoL and did
not find a statistically significant difference. In our opinion the value of spontaneous
movement would be of little importance if it cannot be objectified in QoL measures.
5.4 General limitations, clinical relevance and implications
The most important limitation of this study is the small number of study participants. This
makes it virtually impossible to get statistical significance for any difference found, causes
low levels of power and increases the risk of a type II error (84). Larger study numbers are
however not possible in this region. Pooling of data from multiple centers would be of great
value for future research.
A second limitation is the large amount of missing data. The prime concern is whether the
remaining data are biased (85). The fact that a new set of imagery would be taken and the
relatively confronting questions in the FaCE scale questionnaire could have been a reason for
patients who are not very comfortable with the postoperative result not wanting to participate
in this study. The large travelling distance for most patients to the UMCG could have been an
additional threshold. This means that the data could be biased in favor of content patients. The
benefit of this retrospective study is that it could be performed in a relatively short period of
time. For future research however, prospective standardized data collection would be
favorable.
Lastly, the fact that not one internationally accepted and recognized way to capture progress
in facial paralysis patients exists is a limitation for all research done in facial paralysis. It
causes a myriad of facial assessment tools present amongst facial reanimation surgeons and
makes it very difficult to compare results from different institutions. Furthermore, it is also
one of the causes that the patient material present in our institution did not always perfectly fit
the different assessment tools.
29
Although this study has great limitations, it does give an image of the outcomes of the
dynamic facial nerve reconstructions using a CFNG in the UMCG and Isala Clinics in the past
years. All relevant changes observed point in the direction of improvement of facial
symmetry, as was expected based on the clinical experience. Because of the small number of
participants this study has little clinical relevance. However, several interesting findings have
been done which could lead to more, possibly prospective, future research and, in time,
change treatment strategies.
30
Acknowledgements
I would like to start with a special thanks to the patients that participated in this study, without
them this would not have been possible. Many of the patients lived quite fare away, but the
fact that they were willing to travel to the UMCG meant a great deal to me and shows, I think,
that they also feel that is it very important that all is done it reach the best possible level of
care for facial paralysis.
I would like to express my appreciation to professor dr. P.M.N. Werker (Head of Department
Plastic Surgery, UMCG) for the possibility to perform my research clerkship under his
supervision. His insight in the topic, but also the freedom given to me to form my own
project, were very much appreciated. His enthusiasm for facial nerve reconstructive surgery
has been a source of great inspiration and hopefully the source of new research in this field.
From the department of plastic surgery I would like to thank Dieuwke Broekstra, Msc. for her
help with some of the project design and the correct statistical analysis and Harma Driever for
her help with the guidelines concerning a correct patient information letter.
Lastly I would like to say thanks to the medical photographers, Judith Bender and Henk
Boudewijns, for giving me access to the photo and video material and their genuine interest in
this project.
31
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Appendix I.
Vragenlijst onderzoek aangezichtsverlamming UMCG/Isala
Studienummer: ____
Datum invullen vragenlijst: __ / __ / ____
1. Hoe oud bent u? ______ jaar
(Let op: wanneer u jonger dan 14 jaar bent vragen wij u deze vragenlijsten met hulp van een
ouder in te vullen.)
2. Wat is uw hoogst genoten opleidingsniveau?
o Basisschool
o VMBO
o HAVO/VWO
o MBO
o HBO/Hogeschool
o WO/Universiteit
3. Wanneer is uw aangezichtsverlamming ontstaan?
o Vanaf de geboorte
o Later, namelijk: __________________(datum)
4. Wat is de aangedane kant van uw gezicht?
o Links
o Rechts
o Beide kanten
5. Wat is de oorzaak van uw verlamming?
o Na een operatie: ______________
o Na een ongeval: ______________
o Na een infectie: ______________
o Spontaan/onbekend: ______________
6. Waar bent u geopereerd?
o UMCG
o Isala klinieken
7. Welke operatie heeft u ondergaan?
o Gekruiste aangezichtszenuw (cross-face-nerve-graft)
o Tongzenuw (nervus XII-VII jump anastomose)
o Beiden
o Anders, namelijk: ________________
o Ik weet het niet zeker
8. Heeft u een goudplaatje in het bovenooglid?
o Ja
o Nee
9. Heeft u andere aanvullende operaties ondergaan voor uw aangezichtsverlamming?
o Ja, namelijk: ____________________
o Nee
10. Moet u altijd bewust nadenken om te lachen?
o Altijd
o Meestal
o Soms
o Zelden
o Nooit
11. Bent u tevreden met uw lach?
o Altijd
o Meestal
o Soms
o Zelden
o Nooit
12. Zou u de operatie achteraf nogmaals ondergaan?
o Ja
o Nee, waarom niet? ______________
13. Bent u behandeld door een mime therapeut(e)?
o Ja
o Nee, waarom niet? ______________
Indien u bij vraag 13 ‘Nee’ heeft geantwoord, kunt u vraag 14, 15 en 16 overslaan.
14. Hoe lang bent u behandeld door een mime therapeut(e)? __________________
Kruis een cijfer aan tussen de 0 en 5: 0 = totaal niet mee eens, 5 = helemaal mee eens
15. Ik was erg gemotiveerd voor de mime therapie. 0 1 2 3 4 5
16. De mime therapie heeft bijgedragen aan een goed herstel van mijn 0 1 2 3 4 5
gezichtsfunctie.
17. Geef op de onderstaande lijn aan hoe tevreden u op dit moment bent met het uiterlijk van uw gezicht.
Zeer ontevreden Zeer tevreden
Appendix II. Vragenlijst: “Dutch FaCE Scale”
U heeft deze of soortgelijke vragen misschien al eerder beantwoord. Beantwoord alstublieft ALLE VRAGEN
zo goed mogelijk. De volgende uitspraken gaan over hoe u denkt dat uw gezicht beweegt.
(OMCIRKEL slechts EEN nummer) Eén kant Beide kanten Ik heb geen moeite
Als ik mijn gezicht probeer te bewegen, ondervind ik moeite aan 1 2 0
(Als u problemen heeft aan BEIDE kanten, beantwoord dan de vragen in de rest van de vragenlijst over
de meer aangedane kant, of over beide kanten als ze in gelijke mate aangedaan zijn.) In de
AFGELOPEN WEEK:
(OMCIRKEL slechts EEN nummer per regel) Helemaal
niet Alleen als ik mij
concentreer Een
beetje Bijna
normaal Normaal
1. Als ik glimlach, gaat de aangedane kant van mijn
mond omhoog 1 2 3 4 5
2. Ik kan mijn wenkbrauw optrekken aan de aangedane kant
1 2 3 4 5
3. Als ik mijn lippen tuit, dan beweegt de aangedane kant van mijn mond
1 2 3 4 5
De volgende uitspraken gaan over hoe u zich misschien voelt vanwege de problemen met het
bewegen van uw gezicht. Vult u alstublieft in hoe vaak elk van de volgende uitspraken op u van
toepassing waren in de AFGELOPEN WEEK.
(OMCIRKEL slechts EEN nummer per regel) Altijd Meestal Soms Zelden Nooit
4. Delen van mijn gezicht voelen stijf, vermoeid of ongemakkelijk 1 2 3 4 5
5. Mijn aangedane oog voelt droog of geïrriteerd aan 1 2 3 4 5
6. Als ik mijn gezicht probeer te bewegen, voel ik spanning, pijn of spasme
1 2 3 4 5
7. Ik gebruik oogdruppels of zalf in mijn aangedane oog 1 2 3 4 5
8. Mijn aangedane oog is nat of bevat tranen 1 2 3 4 5
9. Ik gedraag me anders in het bijzijn van mensen vanwege de problemen met het bewegen van mijn gezicht
1 2 3 4 5
10. Mensen behandelen mij anders vanwege de problemen met het bewegen van mijn gezicht
1 2 3 4 5
11. Ik heb problemen met het verplaatsen van voedsel in mijn mond
1 2 3 4 5
12. Ik heb problemen met kwijlen of voedsel en drank in mijn mond houden of met morsen op mijn kin en kleren
1 2 3 4 5
De volgende uitspraken gaan over hoe u zich misschien heeft gevoeld of hoe het met u ging in de
AFGELOPEN WEEK vanwege problemen met het bewegen van uw gezicht. Geef alstublieft aan in
hoeverre u het eens bent met iedere uitspraak:
OMCIRKEL slechts EEN nummer per regel Helemaal
mee eens Mee eens
Weet ik niet
Mee oneens
Helemaal mee oneens
13. Mijn gezicht voelt moe aan en/of als ik mijn
gezicht probeer te bewegen, voel ik spanning, pijn of kramp
1 2 3 4 5
14. Mijn uiterlijk heeft mijn bereidheid om mee te
doen aan sociale activiteiten of familie en vrienden te zien beïnvloed.
1 2 3 4 5
15. Omdat ik moeite heb met mijn manier van eten, heb ik het eten in restaurants of bij andere mensen thuis vermeden
1 2 3 4 5
Aanvullende opmerkingen:
Facial Movement Score = (((Items 1 + 2 + 3) - # valid) / 4 x (# valid)) x 100
Facial Comfort Score = (((Items 4 + 6 + 13) - # valid) / 4 x (# valid)) x 100
Oral Function Score = (((Items 11 + 12) - # valid) / 4 x (# valid)) x 100
Eye Comfort Score = (((Items 5 + 7) - # valid) / 4 x (# valid)) x 100
Lacrimal Control Score = (((Item 8) - # valid) / 4 x (# valid)) x 100
Social Function Score = (((Items 9 + 10 + 14 + 15) - # valid) / 4 x (# valid)) x 100
Total Score = (((sum of all 15 items) - # valid) / 4 x (# valid)) x 100
# valid = number of items the domain for which an adequate response was given.
Appendix III. Dutch Synkinesis Assessment Questionnaire Beantwoord alstublieft de volgende vragen betreffende de functie van uw gezicht, op een schaal van 1 tot 5, volgens de volgende schaal:
1 = zelden of helemaal niet 2 = af en toe of een klein beetje 3 = soms of een beetje 4 = meestal of matig 5 = altijd of ernstig
1 Als ik glimlach, gaat mijn oog dicht 1 2 3 4 5
2 Als ik praat, gaat mijn oog dicht 1 2 3 4 5
3 Als ik fluit of mijn lippen tuit, gaat mijn oog dicht 1 2 3 4 5
4 Als ik glimlach, verstijft mijn hals 1 2 3 4 5
5 Als ik mijn ogen sluit, verstijft mijn gezicht 1 2 3 4 5
6 Als ik mijn ogen sluit, beweegt mijn mondhoek 1 2 3 4 5
7 Als ik mijn ogen sluit, verstijft mijn hals 1 2 3 4 5
8 Als ik eet, traant mijn oog 1 2 3 4 5
9 Als ik mijn gezicht beweeg, ontstaat er een kuiltje in mijn kin 1 2 3 4 5
(Total Synkinesis Score: Sum of Scores 1 to 9 / 45 X 100)