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Objective and Subjective Long Term Outcome of Maxillomandibular Advancement in

Obstructive Sleep Apnea

Cheng-Hui Lin, Wei-Chih Chin, Yu-Shu Huang, Po-Fang Wang, Kasey K. Li, Paola
Pirelli, Yen-Hao Chen, Christian Guilleminault

PII: S1389-9457(20)30227-6
DOI: https://doi.org/10.1016/j.sleep.2020.05.024
Reference: SLEEP 4434

To appear in: Sleep Medicine

Received Date: 23 March 2020

Revised Date: 11 May 2020
Accepted Date: 14 May 2020

Please cite this article as: Lin C-H, Chin W-C, Huang Y-S, Wang P-F, Li KK, Pirelli P, Chen Y-H,
Guilleminault C, Objective and Subjective Long Term Outcome of Maxillomandibular Advancement in
Obstructive Sleep Apnea, Sleep Medicine, https://doi.org/10.1016/j.sleep.2020.05.024.

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 Objective and Subjective Long Term Outcome of Maxillomandibular
Advancement in Obstructive Sleep Apnea

Cheng-Hui Lin1; Wei-Chih Chin2; Yu-Shu Huang1,2*; Po-Fang Wang1; Kasey K. Li3 ;
Paola Pirelli4; Yen-Hao Chen2; Christian Guilleminault5

1. Craniofacial Center, Craniofacial Research Center and Sleep Center, Chang Gung
Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan,
Taiwan.
2. Department of Child Psychiatry and Sleep Center, Chang Gung Memorial Hospital
and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
3. Sleep Apnea Surgery Center, California, USA.
4. Department of Clinical Science and Translational Medicine, University of Rome
"Tor Vergata", Rome, Italy.
5. Stanford University Sleep Medicine Division, Stanford, CA, USA.

*Address correspondence to: Yu-Shu Huang

Department of Child Psychiatry and Sleep Center, Chang Gung Memorial Hospital,

5, Fu-Shing St., Kwei-Shan, Taoyuan 333, Taiwan

Phone: 886-3-328-1200 ext. 8541, Fax: 886-3-318-4541

E-mail: [email protected]

Conflict of Interest: None of the authors has conflict of interest to disclose.

1
Abstract:
Study Objectives:
To evaluate the objective and subjective long-term outcome of maxillomandibular
advancement (MMA) in Far-East Asian patients with moderate to severe obstructive
sleep apnea (OSA).
Methods:
This is a long-term follow-up study to evaluate the treatment outcome of MMA in
OSA patients by objective polysomnography (PSG) and subjective questionnaires
(Pittsburgh Sleep Quality Index-PSQI, Insomnia Severity Index-ISI, Beck Anxiety
Inventory-BAI, Beck Depression Inventory-BDI, Epworth Sleepiness scale-ESS, and
Short Form-36 Quality of Life-SF-36). Evaluation was done before surgery and we
followed these patients one and two years after surgery. We also assessed the
neurocognitive function by Continuous performance test (CPT) and Wisconsin Card
Sorting Test (WCST) before and after MMA.
Results:
A total of 82 patients with OSA (female=19) were enrolled and 53 participants (75.7
% men, age 35.66±11.66 years [mean ± SD], BMI=24.80±3.29) completed the
two-year follow-up. The apnea-hypopnea index decreased from a mean of
34.78±26.01 to 3.61±2.79 and 7.43±6.70 events/hour (p=0.007) at the first and second
year evaluation. There was significant improvement in PSG (especially respiratory
profile), questionnaires (PSQI and ISI total score), and neurocognitive testing
(attention and executive function) after MMA. Meanwhile, no major complication
such as avascular necrosis of bonny segments, facial nerve injury, blindness or
compromise of airway was found after surgery.
Conclusions:
MMA is a clinically effective treatment for patients with moderate-to-severe OSA as
demonstrated by significant long-term decrease in AHI and improvement in
neurocognitive testing.

Keywords:
Obstructive sleep apnea, maxillomandibular advancement, neurocognitive tests,
quality of life, Far-East Asian.

2
Introduction
Obstructive sleep apnea (OSA) is a common sleep disorder characterized by

repetitive upper airway collapse during sleep. Although continuous positive airway

pressure (CPAP) is considered as the first-line treatment for OSA, it is not always

tolerable [1]. Maxillomandibular advancement (MMA, sometimes called bimaxillary

advancement) effectively enlarges the airway in both the palate and tongue regions [2],

by moving the upper jaw (maxilla) and lower jaw (mandible) forward. Compared to

other procedures, it provides the greatest improvement [3] and serves as the most

effective surgical treatment for obstructive sleep apnea [3-5]. It can be performed on

patients with moderate to severe obstructive sleep apnea as monotherapy, or

considered when other procedures fail. In some patients with jaw deformity, it can be

the first-line surgical treatment since significant jaw deformity can contribute to OSA

[4].

An extensive review with meta-analysis performed in 2010 investigated all

published cases at the time and concluded that MMA was the most efficacious surgery

for patients with OSA [4]. Since then, studies have been reported with similar positive

findings. Besides improvement in subjective daytime sleepiness and quality of life [6],

objective findings such as the apnea-hypopnea index (AHI) and co-morbidity such as

elevated blood pressure were also improved after the treatment [3,7-9]. Holty and

Guilleminault reported 1% patients had complication after MMA, and further studies

found low complication rates as well [4]. One common limitation of the studies is the

loss of follow-up, being up to 50 % of the patients.

Most of MMA studies investigated on Caucasian subjects. It is known that

ethnicity can play a role in the therapeutic approach. As example, Far-East Asians

have a very different facial presentation than Caucasians [10]. If a specific maxillary

advancement is needed (up to 10mm as found in the meta-analysis report), facial

3
esthetics may not be easy to achieve even with the usage of counterclockwise rotation

approach. Surgeons in Far-East Asia have proposed specific protocols to allow an

appropriate advancement addressing particularly the maxilla, which is commonly

more retruded in Far-East Asians than in Caucasians. Surgical design uses segmental

maxillo-mandibular rotational advancement with elongation of the posterior maxilla

to achieve counterclockwise rotation of the maxillo-mandibular complex (MMC)

pivoted on the nasion (a common approach). If necessary, after determination of the

direction of the rotation after osteotomy of both jaws (based on cephalometric

findings and identification of an edentulous space) or extraction of bilateral premolar

teeth, a segmental osteotomy of the maxilla is performed to foster further

advancement of posterior segment, including posterior nasal spine as previously

reported [1-10]. However, with a clear literature indicating beneficial effects of

positive-airway-pressure therapy on performance and cognition in OSA patients

[11,12], there is absence of data about this surgical aggressive procedure on these

common complaints of patients.

Therefore, the purpose of this study was to observe the long-term outcomes of

MMA, using polysomnography (PSG), as well as questionnaires and neurocognitive

function tests. We also examined the long-term complications of MMA and discussed

about facial esthetic issue for Far-East Asians.

Methods
All patients were evaluated initially at the sleep clinic in a medical center with

complaints related to sleep-disordered breathing. They must undergo assessment of

"ear-nose-throat" (ENT) by an ENT doctor and OSA-related symptoms by sleep

specialists, investigation of the oral-facial structure by a plastic craniofacial surgeon

and orthodontist, and mental evaluation by psychiatrists with sleep medicine specialty.
4
All subjects received the same evaluations and tests before MMA and were followed

at the first and second year after surgery.

MMA patient selection criteria:

To be considered as a potential candidate for MMA, patients must be between

age 18 to 65, with body-mass-index (BMI) below 30 kg/m2, and with AHI at least 10

events/hour. They must present evidence of retruded jaws at clinical evaluation.

Patients were excluded if:

• Patients had cleft lip/palate or other craniofacial syndromes.

• Patients had tumor formation, hypertrophic adenoids and/or tonsils in the pharyngeal

airway, confirmed by nasopharyngoscopic examination.

• Patients received soft-tissue airway surgery within one year or had postsurgical scar

formation with contracture band.

• Patients had oral infection or other infection that would preclude jaw surgery.

• Patients had other conditions or major systemic diseases that would place the

subjects at a higher mortality or morbidity risk for the procedure.

Evaluation Tools:

(1) Polysomnography: Objective standard overnight polysomnographic evaluation

was performed. It involved systematic monitoring of the following variables: 4

electroencephalogram (EEG) leads, 2 electro-oculogram (EOG) leads, chin and

leg electromyogram (EMG) leads, and 1 electrocardiogram (ECG) lead;

respiration was monitored with a nasal cannula pressure transducer, a mouth

thermistor, thoracic and abdominal inductive plethysmography bands, a finger

oxygen saturation (MasimoTM) oximeter with derivation of oximetry and finger

plethysmography signals, a neck microphone, diaphragmatic-intercostal,

5
 abdominal muscle EMGs, and a transcutaneous CO2 electrode; leg EMGs were

also monitored. Subjects were continuously video monitored during the

recording. Recordings were performed following the recommendation of the

American-Academy of Sleep-Medicine-AASM and PSG scoring was done

following also AASM recommendations with hypopnea scored for either a 3%

oxygen saturation drop or an arousal response [13,14]. All subjects received

PSG before MMA and 0.5, 1, and 2 years after MMA.

(2) Subjective questionnaires: All subjects filled questionnaires including Epworth

Sleepiness Scale (ESS) [15], Pittsburgh Sleep Quality Index (PSQI) [16],

Insomnia Severity Index (ISI) [17], the Beck Anxiety Inventory (BAI) [18], the

Beck Depression Index (BDI) [18] and short form of quality of life (SF-36)

[19]. The ESS has 8 questions and a total score over 10 indicates daytime

sleepiness. PSQI is an effective instrument measuring the quality and patterns

of sleep in adults. The ISI evaluates the severity of insomnia and the higher

total score means the severe clinical insomnia. The BAI is a self-report measure

of anxiety and the score of 36 and above is potentially concerning levels of

anxiety. The BDI is a self-reported measure of depression and the score of 17

and above is potentially concerning levels of clinical depression. The SF-36 is a

questionnaire of Short Form-36 quality of life with 8 domains. The higher the

score, the better the result.

(3) Neurocognitive tests:

(a) Continuous performance task (CPT): Computerized CPT is a vigilance or

attention test for research and clinical settings. It measures the subject’s

attention in three domains: inattention, impulsivity and vigilance. It involves the

presentation of target and non-target stimuli. The test runs for 15 minutes and

primarily assesses attention and impulse control. Multiple dependent measures

6
 exist, and commonly used indices include omissions, commissions, and

detectability (D’). The result of CPT score is presented in T-scores. High

T-scores indicate an attention problem, with any T-score >60 considered as

abnormal. The high T score of omissions, commissions, Hit reaction time (RT),

Hit RT standard (Std.) Error, variability, detectability, Hit reaction time

inter-stimulus-interval Change (Hit RT ISI Change) and Hit Std. error

inter-stimulus-interval Change (Hit SE ISI Change) indicate inattention High

commission, Hit RT and Perseveration indicate high impulsivity, and High Hit

reaction-time RT block change (Hit RT block change) and Hit Std. error (SE)

block change indicate poor vigilance [20].

(b) The Wisconsin Card Sorting Test (WCST): Computerized WCST measures

the subject’s executive function by assessing planning ability, organizational

skills, abstract reasoning, concept formation, cognitive set maintenance and

shifting ability, and inhibition. The Total Errors scores is an overall score of

WCST, and higher score indicates worse performance. “Perseverative Response”

and “Perseverative Error T score” are higher in subject with worse performance

of mental flexibility and insight. “Non-Perseverative Error” reflects difficulty to

forming concepts and insight even in flexible answer. “Conceptual-Level

Response score” indicates the insights in correct principle of card combination.

“Learning to learn” depicts the average tendency over successive categories for

efficiency to change [21].

All subjects that decided to undergo MMA and responded to inclusion and

exclusion criteria were asked to fill all questionnaires and receive neurocognitive

functions tests (CPT and WCST) before, one and two years after MMA to avoid

practice effects. The study was approved by the institutional review board of Chang

7
Gung Memorial Hospital (CGMH #201701056B0).

Treatment:

Once evaluations and diagnosis of OSA were affirmed, the issue of treatment

was considered and discussed with the patients. Positive-Airway-Pressure (PAP)

treatment was always offered as the first line treatment, but some patients failed such

treatment or wanted to consider other options such as MMA.

The surgical design in our study added two parts to MMA. One was the

counterclockwise rotation, and the other was the segmental osteotomy of maxilla

and/or mandible. All the included patients had counterclockwise rotation of MMC.

Further segmental osteotomy was applied to patients with velopharyngeal narrowing

or due to occlusal problems (Figure 1) [22]. Computer aided surgical simulation was

applied in the planning process and generation of surgical splints.

The surgical procedures commonly start with bilateral sagittal splits of mandible,

followed by LeFort I (with segmental osteotmies as indicated) osteotomy of maxilla.

On mandible, the split technique of Hunsuck is applied with the purpose of preserving

medial gonion, the insertion of medial pterygoid muscle, to the proximal segment

after osteotomy [23]. Keeping muscle insertions away from distal segments may

facilitate easy telegnathic advancement of mandible. On maxilla, meticulous

dissection of great palatine neurovascular bundles and preservation of soft tissue

connections between segments ensure the sensory and circulation supply to each parts

of maxilla after large advancement [24]. The maxillomandibular complex is secured

with plates and screws. A trapezoid mortise or triangular genioplasty can be

supplemental procedures to reinforce muscular tensions on genioglossus and

geniohyoid musculatures and keep the tongue forward [25].

Perioperative management includes humidified oxygen, pulse oximeter

monitoring, prophylactic antibiotics, pain medications, antifibrinolytics,

8
corticosteroids, antiemetics, keeping head-up position, and facial ice-packing. Along

with substantial advancement of MMC, extubation of nasotracheal tube is conducted

after every patient emerging from anesthesia. After one to two hours of observation in

the recovery room, the patient is moved to ward for post-operative care. The patient

may proceed to oral cleansing, water drinking and liquid diet. Commonly, the patient

may get off bed in the next morning. Following two to three nights of stay in the ward,

usually, the patient can be discharged. One month after the surgery, most of the

patients can gradually adapt to regular diet.

The patients are requested to come back for follow-up at one week, two weeks,

one month, three months, six months, and every six months thereafter till the

orthodontic treatment completes and stable dentoskeletal occlusion achieved. At

follow-up visits, complications under monitoring include sensory disturbance of the

2nd and 3rd branches of trigeminal nerve, symptom/sign of infection, soft tissue

swelling, undesirable facial esthetics, Eustachian tube malfunction, plates or screws

exposure, skeletal relapse, avascular necrosis of bonny segments, malunion, condylar

disorder, malocclusion, bleeding, facial nerve dysfunction, optic nerve disturbance, or

airway compromise.

Statistical analysis:

Analyses were performed using the SPSS version 18. The data were shown as

means±standard deviation. Student t-tests for repeat measures were used to compare

the findings before, one and two years after treatment for questionnaires and

neurocognitive performance tests. Analysis of variance with post hoc analysis with

Bonferroni correction was performed on the different scales that were obtained at

entry, one and two years after treatment. Only PSG had 0.5 year test after surgery. The

correlations were performed by Pearson’s correlation and Spearman’s correlation tests.

9
All the reported p-values were two-tailed with statistical significance set at <0.05.

Results
A total of 82 patients (19 females) underwent MMA during the time of the data

collection. 53 patients (13 females) received the complete two-year follow-up, and the

mean age± standard-deviation-SD at entry was 35.66±11.66 years.

In average, maxilla (at A point) and mandible (at B point) were advanced

4.3±2.9mm and 13.3±3.8mm respectively. The counterclockwise rotation of

maxillomandibular complex (MMC) was 6.1±3.4. The pharyngeal airway space

increased 6.3±3.5mm and velopharyngeal airway increased 4.2±2.8mm.

None of the patients had major complications such as massive bleeding, avscular

necrosis of bonny segments, facial nerve palsy, optic nerve disturbance, or airway

compromise after surgery. However, variable degree of sensory disturbance of 2nd (3

patients) and 3rd (79 patients) branches of trigeminal nerve was noted perioperatively.

Gradual recovery was observed during the follow up period. Soft tissue swelling

reached plateau within three days after surgery, and subsided within three months.

Subclinical infection with focal tenderness on right cheek was observed in one patient

at three months after surgery, and symptoms were relieved after oral antibiotic

treatment. One patient complained about off-and-on E-tube dysfunction, which was

improved by otolaryngological treatment. More than half of the patients reported

aesthtic improvement. None of them requested revisional surgery due to aesthetic

concerns. During the follow-up period, the skeletal relapse was limited within 1mm.

All patients completed orthodontic treatment within two years after surgery.

Table 1 presented the results of PSG. There was a clear response and

improvement to MMA, shown by the decrease in AHI (p=0.007), and the

improvement of many respiratory-related items including respiratory disturbance

index (RDI), apnea index (AI), desaturation Index, and mean oxygen saturation (SaO2)
10
while BMI did not change significantly. The AHI decreased from a mean of

34.78±26.01 to 3.61±2.79 and 7.43±6.70 events/hour (p=0.007) at the first and second

year evaluation (Figure 2). Other sleep variables of PSG also showed significant

changes including decreased arousal index (p<0.001), decreased snore index

(p=0.035), decreased systolic pressure (p=0.022) and increased stage N2 sleep.

The objective findings of PSG correlated with subjective scales. Not only the ISI

(p=0.002) was improved after MMA at the first year, but also the subjective sleep

quality and the global score of PSQI was significantly improved at the first and

second year follow-up (p<0.001; p=0.001) (Table 2). The sleep disturbance of PSIQ

was also significantly improved at the second year. Although ESS, BAI and BDI did

not have significant improvement, the total scores of these scales decreased after

MMA. SF-36 did not improve significantly after MMA, but the scores of all subscales

increased at the 1st and the 2nd year follow-up after MMA (Table 3).

The neurocognitive testing (Table 4) indicated improved cognitive performance

at the first and second year after MMA in several aspects. The CPT scores showed

significantly improvement in subscales including Confidence Index, Omission T score,

Hit RT Std. Error T score, Variability T score, Hit RT Std. Error percentile and

variability percentile (p=0.01,<0.001,<0.001,0.005,<0.001,0.024) and all other

subscales of CPT showed non-significant improvement. The WCST scores also

showed better performances at all subscales, and there were significant changes at all

subscales at the second year follow-up (T scores >50).

Discussion
Although we recruited 82 patients receiving MMA, the loss of patients during

the two-year follow-up reached to 35.4%. This study had several limitations. First is

the gender ratio and more males (75.7%) were included. Second, this was not a
11
case-control study, and we did not compare MMA with other treatments such as

CPAP. Although some of our patients tried to use CPAP before surgery, the poor

usage of CPAP and the preference of surgery limited further investigation and

analysis. Last, we only did neurocognitive tests and did not use image studies to prove

the improvement of neurocognitive function after MMA.

In this study, CPT and WCST were used to investigate cognitive performances

including attention and executive function, and the results demonstrated patients’

cognitive function was clearly improved one and two years after MMA. Besides

objective decrease in AHI, subjective sleep was also improved and shown by

questionnaires. Our findings were similar to previous studies and showed that MMA

could be a very effective surgical treatment for OSA [3,4,9]. Our results also showed

that two years after MMA, most patients (64.15%) still maintained the treatment

effect and did not have significant recurrence (AHI=7.43±6.7/hour). Only 17 patients

had AHI greater than 5 at the first- or second-year follow-up after MMA. Most of

them had mild OSA and only two had AHI greater than 15 after MMA. There was no

body weight (BMI) change before and after MMA and thus the treatment effect was

not related to BMI change. Moreover, there was no complication in our patients

undergoing MMA. Although the increase in AHI is not significant after two-year

follow-up, further follow-up is needed for possible relapse. Future research is needed

to clarify the risk factors and underlying causes of relapse after MMA.

Ethnicity is a noteworthy factor. MMA can be more complex in Far-East Asians

due to the ethnic facial presentation. More efforts must be paid to address not only the

upper-airway problem but also a valid esthetic presentation. We have previously

reported our surgical technique that could avoid to impact the facial balance and have

a sufficient airway widening at the same time.22

Most previous studies evaluated the impact of CPAP on cognition of Caucasian

12
patients with OSA [26-29], and the results highlighted the detrimental effects of OSA

on neurocognitive symptoms, including memory, psychomotor speed, executive

functioning, attention, processing, reasoning, and psychomotor speed. Improvement

in neurocognitive functions was demonstrated also on the Caucasian groups with the

usage of CPAP. The efficacy of dental devices has also been explored and compared

to the results of CPAP. A randomized controlled trial evaluating effectiveness of oral

appliance therapy versus CPAP with overnight in-laboratory polysomnograms

reported that both therapies improved neurobehavioral domains and quality of life

scores [30]. However, the effect of CPAP was greater and able to provide more

complete resolution of OSA. Investigation with the combined use of

neuropsychometric testing and imaging has also been performed. Castronovo et al.,

published the first study using functional magnetic resonance imaging to compare

brain activation in OSA patients versus healthy controls during a cognitive test of

working memory (n-back task). After three months of CPAP treatment, no difference

was found in n-back task testing [31-33]. However, other cognitive testing showed

improvement in the OSA group with greater activation in the left frontal cortex, medial

precuneus, and hippocampus, and decreased activations in the caudal pons. This was

interpreted as a compensatory over-recruitment, as decreased activation in prefrontal

and hippocampal structures were observed after treatment [31].

The computerized CPT is a vigilance and sustained attention test for research and

clinical settings. The WCST test has been widely utilized to measure executive

function by assessing planning ability, organizational skills, abstract reasoning,

concept formation, cognitive set maintenance and shifting ability, and inhibition.

Before surgery, our patients presented impairments at many subscales, which can be

related to the daytime sleepiness and the direct impact of desaturation during sleep.

OSA has been known to inflict detrimental effects shown by tests of sustained
13
attention, visuospatial learning, executive function, motor performance and

constructional abilities [34] and it has also been confirmed by a recent meta-analysis

[35]. Our study results showed similar findings in Far-East Asians before MMA, and

also found noticeable improvement one or two years after MMA. Although no brain

imaging was performed in this study, the recurrence rate of MMA was low and there

were no compliance issue. Therefore it can be speculated that long-term

neurocognitive effects are the same as CPAP.

After MMA, both PSQI and ISI have improved and it was comparable to the

findings of PSG. BDI, BAI and SF-36 were performed in this study to evaluate mood

and quality of life. The score of these questionnaires were improved after surgery, but

non-significantly. The ESS didn’t have significant improvement as well. Although

there was no study investigating BDI and BAI change after MMA, most previous

studies investigating daytime sleepiness and quality of life showed improvement after

MMA. Our patient population can be different from those in previous studies not only

in ethnic. They were relatively younger and thinner than “typical” OSA patients.

Besides, all our subjects did not have depression or anxiety disorder before and it

could also partially explain these findings. Depression or anxiety can be comorbid

with OSA, and other demographic variables can correlate with daytime sleepiness,

quality of life and the treatment effect of MMA in OSA patients. Further investigation

and comparison of different groups of patients can help us evaluate the impact of

MMA and confounding factors of the treatment.

Our results were consistent with the improvements noted in previous studies.

Although PAP treatment is considered the "gold standard," its compliance can be a

drawback. Our results indicated that MMA is a clinically effective treatment for

Far-East Asian patients with moderate to severe OSA with long-term treatment effect,

as evidenced by the significant reduction in AHI and the significant improvement in

14
neurocognitive testing.

Acknowledgements: The conception and design of this study was by Professor

Guilleminault before his passing. Part of the article was also written by him. Although

he could not be the corresponding author, we would like to thank and honor him. He

was the most important and fundamental person for this research. Without his

inspiration and vision, it could not be completed.

This study was supported by Chang Gung Memorial Hospital grant #:

CRRPG5C0311~3 to CH Lin, and CRRPG5C0171~3 to YS Huang. None of the

authors has financial interest relevant to this article to disclose. None of the authors

has conflict of interest to disclose.

Author contributions:
• Conception or design of the work: Christian Guilleminault, Yu-Shu Huang

• Data collection: Yu-Shu Huang, Cheng-Hui Lin, Wei-Chih Chin

• Data analysis: Yen-Hao Chen

• Drafting the article: Yu-Shu Huang, Christian Guilleminault, Cheng-Hui Lin

• Edit manuscript: Kasey K. Li

• Critical revision of the article: Cheng-Hui Lin, Yu-Shu Huang, Kasey K. Li

• Final approval of the version to be published: Yu-Shu Huang

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Figure Captions:

Figure 1. Surgical design of segmental maxillomandibular rotational advancement

(SMMRA).22 SMMRA uses intrusion of the anterior segment (1) and elongation of
the posterior segmented maxilla (2) to achieve counterclockwise rotation (3) of the
maxillomandibular complex (MMC), pivoted on Nasion (N). (a) Cephalometric
simulation illustrated the tooth to be extracted (x) and the related bony segment to be
removed (slashed area). The direction of rotation after osteotomy on both jaws was
demonstrated (curved dash arrows). (b) The segmental osteotomy of the maxilla uses
an extraction (x) or edentulous space to facilitate further advancement of posterior
segment, including posterior nasal spine. (c) The counterclockwise rotation of
maxillomandibular complex reinforces the mandibular advancement to a distance
more than could be achieved in ordinary orthognathic surgery performed for the
correction of Class II malocclusion. N= nasion; B= B point; A= A point; PNS=
posterior nasal spine.

Figure 2. The change of AHI after MMA surgery. AHI: apnea-hypopnea index; MMA:
maxillamandibular advancement.

19
Table 1. Demography data and PSG data of subjects received MMA surgery
(total N=82) Pre OP Post OP Post OP Post OP 2 years p value
1
Male=63 (N=53) 0.5 year 1 year (N=53)4
(76.8%) (N=53)2 (N=53)3
Age (mean+SD) 35.66±11.66 - - -
Sex (male)% 40(75.7%) 40(75.7%) 40(75.7%) 40(75.7%)
BMI 24.80±3.29 24.28±2.73 24.67±3.12 23.90±4.67 0.216
AHI ( events/hr) 0.007*
34.78±26.01 2.63±5.91 3.61±2.79 7.43±6.70
(1>2,3,4)
RDI(events/hr) 0.007*
43.68±22.30 11.98±11.53 15.24±9.75 15.61±9.58
(1>2,3,4)
AI(events/hr) 0.001*
15.98±19.63 1.05±3.20 1.36±2.11 2.89±4.57
(1>2,3,4)
Desaturation 0.044*
29.40±27.70 3.51±7.60 4.51±4.54 6.61±7.10
Index(events/hr) (1>2,3,4)
Sleep Efficiency 0.625
75.08±12.96 80.88±11.60 79.12±16.17 73.51±21.53
%
PLMS Index <0.001*
0.40±1.33 3.04±5.84 16.74±6.97 2.01±4.57
(events/hr) (1,2,4<3)
Stage N1 (%) 0.058
41.08±16.47 19.01±8.52 23.71±10.17 25.51±17.15
(1>2,3)
Stage N2% 0.037*
36.39±11.59 54.37±13.22 51.91±14.38 50.78±17.20
(1<2,3)
Stage N3% 7.37±7.18 10.25±9.30 7.64±9.23 7.46±7.65 0.310
TST (minutes) 278.73±49.59 304.36±40.60 301.45±55.61 281.68±70.92 0.819
REM % 15.14±4.01 16.36±5.23 16.74±6.97 16.22±6.11 0.666
Arousal <0.001*
42.53±17.15 19.68±9.98 20.02±7.46 19.28±8.43
Index(events/hr) (1>2,3,4)
Snore 327.08±239.2 0.035*
65.76±83.79 114.9±100.67 146.37±117.94
Index(events/hr) 5 (1>2,3)
Mean heart rate 69.70±9.75 61.00±7.66 63.18±8.07 64.98±9.33 0.051
Systolic 0.022*
129.20±13.89 118.40±17.60 121.20±18.62 119.60±18.97
pressure (1>2)
Diastolic 0.155
78.60±15.20 72.70±11.78 79.50±10.37 74.80±11.49
pressure
Mean SaO2 (%) 93.91±3.59 95.91±1.38 96.18±1.72 95.64±1.69 0.028*
20(1<2,3,4)
Repeat measure : *p<0.05 ;
PSG: polysomnography; MMA: maxillamandibular advancement; OP: operation; BMI:
body-mass index; AHI: apnea-hypopnea index; RDI: respiratory disturbance index; AI: apnea
index; REM: rapid eye movement; TST: Total Sleep Time; PLMS: Periodic Limb Movement
Syndrome; Mean SaO2: mean oxygen saturation; hr: hour; SD: standard deviation.

21
Table 2. The subjective questionnaire results of PSQI , ISI, BAI , BDI and ESS
(N=53) Pre OP1 Post OP Post OP p value
1 year2 2 year3
<0.001
PSQI-Subjective sleep quality 1.95±0.79 1.05±0.65 1.27±0.78 *
(1>2,3)
0.052
PSQI-Sleep latency 1.00±0.87 0.86±0.77 0.69±0.65
(1>3)
PSQI-Sleep duration 1.13±0.81 1.00±0.60 1.05±0.85 0.817
PSQI-Habitual sleep efficiency 1.07±1.31 0.54±0.84 0.87±0.81 0.141
0.010*
PSQI-Sleep disturbances 1.39±0.77 1.13±0.46 0.94±0.43
(1>3)
PSQI-Use of sleeping 0.678
0.33±0.87 0.43±1.03 0.50±0.83
medication
PSQI-Daytime dysfunction 1.26±0.92 1.05±0.90 1.23±0.72 0.498
0.001*
PSQI global score 8.71±3.71 5.86±2.41 6.55±3.20
(1>2,3)
0.002*
ISI total 12.79±6.12 8.78±7.00 10.73±6.26
(1,3>2)
BAI 6.09±7.81 4.57±6.02 4.55±7.69 0.672
BDI 11.88±10.04 9.70±10.13 12.87±12.08 0.123
ESS 10.78±5.00 9.47±5.21 10.24±5.14 0.137
Repeated measure : *p<0.05 ;
MMA: maxillamandibular advancement; OP: operation; PSQI: Pittsburgh Sleep Quality
Index; ISI: The Insomnia Severity Index; BAI: Beck Anxiety Inventory;
BDI: Beck Depression Inventory; ESS: Epworth Sleepiness scale;

22
Table 3. The SF-36 quality of life results before and after MMA
(N=53) Pre OP1 Post OP Post OP p value
1 year2 2 year3
SF-36_PF 89.38±21.05 89.38±19.65 89.56±24.54 0.717
SF-36_RP 68.75±43.30 76.56±42.30 81.25±40.31 0.417
SF-36_BP 91.71±18.64 93.28±11.82 93.13±12.57 0.805
SF-36_GH 58.13±29.83 68.44±22.19 66.25±27.05 0.259
SF-36_VT 54.38±28.04 61.88±30.98 62.19±29.10 0.315
SF-36_SF 70.31±28.46 78.91±32.18 80.47±31.61 0.218
SF-36_RE 66.67±47.14 81.25±40.31 83.33±36.51 0.256
SF-36_MH 61.75±23.50 66.75±25.50 64.25±19.24 0.644
Repeated measure: *p<0.05; SF-36: is a questionnaire of Short Form-36 quality of
life; MMA: maxillamandibular advancement; OP: operation; PF: Physical
Functioning; RP: Role Physical; BP: Bodily Pain; GH: General Health; VT: Vitality;
SF: Social Functioning; RE: Role Emotional; MH: Mental Health.

23
Table 4 The result of neurocognitive test before and after MMA
(N=53) Pre OP Post OP Post OP p value
1 year 2 year
CPT test Mean +SD Mean +SD Mean +SD
0.010*
CPT Clinical, Confidence Index 47.49+14.54 41.74+16.01 40.65+17.05
(1<2,3)
<0.001*
CPT # Omission T score 47.10+14.04 43.67+4.99 44.36+5.68
(1<2,3)
CPT # Commissions T score 44.59+12.61 41.79+7.55 43.75+8.98 0.234
CPT Hit RT T score 52.75+13.98 50.96+11.56 49.89+15.16 0.248
<0.001*
CPT Hit RT Std. Error T score 52.80+12.86 44.06+12.22 44.19+13.48
(1<2,3)
0.005*
CPT Variability T score 47.73+11.22 42.00+9.26 41.73+2.29
(1<2,3)
CPT Detectability T score 47.04+10.57 38.42+5.08 38.42+5.08 0.411
CPT Response Style T score 51.42+12.56 51.20+15.13 51.93+11.01 0.079
CPT Perseverations T score 54.23+12.69 38.16+14.61 45.21+1.21 0.640
<0.001*
CPT Hit RT Std. Error percentile 55.53+33.57 32.79+28.90 33.15+31.45
(1<2,3)
0.024*
CPT Variability percentile 43.63+31.62 27.58+25.46 25.78+2i.00
(1<2,3)
WCST test
Total Errors T scores 44.35+11.88 48.15+10.84 50.00+12.50 0.001*
% Error T scores 44.65+11.74 48.40+11.01 50.36+12.76 0.001*
Perseverative Response T scores 44.15+10.88 47.75+12.44 50.71+13.80 0.001*
% Perseverative Response T
44.05+11.12 48.35+12.50 50.36+13.05 <0.001*
scores
Perseverative Errors T scores 44.00+11.24 48.05+12.13 50.79+13.58 <0.001*
% Perseverative Errors T scores 44.25+11.58 48.90+12.43 50.93+13.12 <0.001*
% Conceptual Level Response T
44.65+11.68 48.65+10.89 50.71+12.34 <0.001*
scores
% Errors percentiles 38.80+30.29 49.10+27.77 54.79+29.99 <0.001*
Perseverative Response
36.55+28.54 49.40+30.10 53.93+32.10 0.001*
percentiles
% Conceptual Level Response
38.60+30.33 49.25+28.16 55.71+29.28 <0.001*
percentiles
Repeated measure : *p<0.05 ;

24
MMA: maxillamandibular advancement; OP: operation; CPT: Continuous Performance Test;
WCST: Wisconsin Card Sorting Test; SD: standard deviation; RT: reaction time; Std.:
standard.

25
This two-year study evaluated maxillomandibular advancement in Asian
patients.
Significant improvements in variables of PSG were found.
Subjective sleep and neurocognitive function testing were also improved.
MMA is effective for Asian sleep apnea patients.
Author contributions:
• Conception or design of the work: Christian Guilleminault, Yu-Shu Huang

• Data collection: Yu-Shu Huang, Cheng-Hui Lin, Wei-Chih Chin

• Data analysis: Yen-Hao Chen

• Drafting the article: Yu-Shu Huang, Christian Guilleminault, Cheng-Hui Lin

• Edit manuscript: Kasey K. Li

• Critical revision of the article: Cheng-Hui Lin, Yu-Shu Huang, Kasey K. Li

• Final approval of the version to be published: Yu-Shu Huang