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each patient. Secondary outcomes included surgical success, defined as the
percentage of patients with more than 50% reduction of the AHI to fewer than
20 events/h, and OSA cure, defined as a post-MMA AHI of fewer than 5 events/
h. Forty-five studies with individual data from 518 unique patients/interventions
were included. Among patients for whom data were available, 197 of
268 (73.5%) had undergone prior surgery for OSA. Mean (SD) postoperative
changes in the AHI and RDI after MMA were -47.8 (25.0) and -44.4 (33.0),
respectively; mean reductions of AHI and RDI outcomes were 80.1% (1.8%)
and 64.6% (4.0%), respectively; and 512 of 518 patients (98.8%) showed
improvement. Significant improvements were also seen in the mean
(SD) postoperative oxygen saturation nadir 70.1% to 87.0% and Epworth
sleepiness scale score of 13.5 to 3.2. Rates of surgical success and cure were
389 (85.5%) and 175 (38.5%), respectively, among 455 patients with AHI data
and 44 (64.7%) and 13 (19.1%), among 68 patients with RDI data. Preoperative
AHI of fewer than 60 events/h was the factor most strongly associated with the
highest incidence of surgical cure. Nevertheless, patients with a preoperative
AHI of more than 60 events/h experienced substantial net improvements despite
modest surgical cure rates. Maxillomandibular advancement is an effective
treatment for OSA. Most patients with high residual AHI and RDI after other
unsuccessful surgical procedures for OSA are likely to benefit from MMA
(Zaghi et al.
).2016
Camacho et al. performed a meta-analysis to examine outcomes in the
intermediate-term (1 to <4 years), long-term (4 to <8 years), and very long-
term (≥8 years) for maxillomand ibular advancement (MMA) as a treatment for
OSA. The a uthors systematically reviewed the international literature through
July 26, 2018. Out of 445 studies screened, 6 met the criteria (120 patients).
Thirty-one patients showed a reduction in AHI from a mean 48.3 events/h (95%
CI, 42.1–54.5) pre-MMA to 8.4 (95% CI 5.6, 11.2) in the intermediate term.
Fifty-four patients showed a reduction in AHI from a mean 65.8 events/h (95%
CI, 58.8–72.8) pre-MMA to 7.7 (95% CI 5.9, 9.5 in the long term. Thirty-five
showed a reduction in AHI from a mean 53.2 events/h (95% CI 45, 61.4)
12 Advances in the Surgical Treatments for Snoring and Obstructive Sleep Apnea 191
Romano et al. published a long-term follow-up of patients who had
maxillomandibular advancement for the treatment of obstructive sleep apnea
syndrome (retrospective study). A total of 19 patients with severe OSAS were
treated during the period 2007–2016. They were followed up 6 months postop-
eratively (T1) and after a mean follow-up of 6.7 (range 4–10) years (T2, between
November 2017 and February 2018) for the polysomnography variables, and the
Epworth sleeping scale (ESS) and body mass index (BMI) were recorded. All
polysomnographic variables improved significantly from baseline to T1 and
from baseline to T2. The ESS significantly improved from baseline to T2. Nearly
all patients at T1 and over two-thirds at T2 had a 50% reduction of the apnea/
hypopnea index when compared with baseline, and a value lower than 20 of the
same indexes. The BMI did not change significantly from T0 to T2. Their long-
term follow-up has documented the stability of the outcomes of the MMA for the
treatment of OSAS (Romano et al. 2020).
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pre-MMA to 23.1 (95% CI 16.3, 29.9) in the very long term. Improvement in
sleepiness was maintained at all follow-up periods. The lowest oxygen saturation
improvement was maintained in the long term. Authors observed that while
patients treated with MMA maintained improvements in AHI, sleepiness, and
lowest oxygen saturation in the long term; mean AHI increased to moderate
OSA in the long term (Camacho et al.
). MMA is an effective surgical
option for patients with OSA. However, the nasal changes associated with
significant maxillary advancement are an important concern. In a study of
379 subjects 71 (18.7%) underwent corrective nasal surgery with a median
time to surgery of 10.5 months. Ten patients (2.6%) required a second corrective
nasal operation (Liu et al. ).2017a
2019
192 A. Khan and M. Hunasikatti
(b) Distraction osteogenesis maxillary expansion (DOME)
(c) This surgical technique is recommended for adult individuals who have OSA
who are identified to have narrow nasal floors and high-arched palate without
soft tissue redundancy. Stanley Yung-Chuan Liu, MD, DDS et al., conducted a
prospective cohort of 20 subjects, who underwent DOME (Liu et al.,
2017b).
This technique involves placement of a maxillary expander with mini-implants
to custom fit the narrow palate under local anesthesia, followed by LeFort level
1 osteotomy via small incisions. After wedging the mid-palatal suture, an
expander is turned to ensure separation of the maxilla (1 mm diastema). Patients
then turn the expander daily by 0.25 mm. One month after the surgery, ortho-
dontic treatment is required to close the gap between maxillary incisors. The key
feature of distraction osteogenesis is the incremental traction to the reparative
callus that then initiates adaptive changes in the soft tissues. Authors report that
“separation of mid-palatal suture and subsequent maxillary and nasal floor
expansion was successfully achieved in all subjects.” Authors also noted signif-
icant reductions in outcome measures of ESS: Before 12.3 ± 4.10, After
7.8 ± 4.8; NOSE: Before 11.7 ± 5.3, After 3.85 ± 3.23; AHI: Before
30.9 ± 27.1, After 14.2 ± 9.3; oxygen desaturation index (ODI): Before
23.0 ± 28.4, After 8.7 ± 6.9, and nasal airflow resistance. These results need
to be interpreted with the knowledge that expanders remain in place for 8 months
and longer-term data is not available to observe the rate of relapse (Liu et al.
2017a)
A systemic review by Wai Kin Tsui et al. (published online in 2016) showed
that mandibular distraction osteogenesis (MDO) was effective in resolving OSA
in adults with the retrognathic mandible. From this review, authors concluded
that MMA could enlarge the airways in three dimensions by expanding the
skeletal framework, thus rendering the pharyngeal soft tissues and tongue more
resistant to collapse during inspiration. Out of 534 studies, only 98 were found to
be relevant to the treatment of OSA with MDO. Only 12 articles fulfilled the five
criteria and entered the final round of appraisal. All 12 studies were retrospective
and were on adults with unilateral or bilateral temporomandibular joint (TM J)
ankylosis with associated retrognathic mandible and OSA. All 12 studies used
pre and postintervention polysomnograms (PSGs). Significant improvement was
reported for AHI/RDI in the adult group from 51.7/h (43.0–58.0/h)
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pre-operatively to 2.9/h (2.1–3.4/h) postoperatively. The lowest oxygen satura-
tion improved in adults from 66% to 77% preoperatively to 90.3% to 98.2%
postoperatively. Although this review demonstrates the effectiveness of the
procedure, the evidence-based data on MDO is believed to be weak (Tsui
et al.
2016).
12 Advances in the Surgical Treatments for Snoring and Obstructive Sleep Apnea 193
12.7 Upper Airway Stimulation for Obstructive
Sleep Apnea
A relatively new development in the armamentarium of treatments for OSA is upper
airway stimulation which involves unilateral respiration synchronized stimulation of
the hypoglossal nerve delivered via an implanted neuromodulation technology. The
procedure requires placing a cuff electrode on the distal branches of the hypoglossal
nerve to stimulate the tongue protrusers (genioglossus and transverse/vertical mus-
cles), inserting an implanted pulse generator in the right upper chest, and placing a
respiratory sensing lead between external and internal intercostal muscles of the ribs.
From July 2014 through October 2015, 60 patients were enrolled in a prospective
single-arm study conducted by Heiser, MD et al. The study enrolled subjects with
moderate-to-severe OSA, AHI: 20–65, failure of CPAP therapy, body mass index
(BMI) ≤ 32 kg/m
2
, and absence of complete circumferential collapse on drug-
induced sleep endoscopy. All patients had failed CPAP as first-line therapy,
14 had attempted oral appliance therapy, and 15 had prior upper airway OSA
operations (UPPP, uvulopalatal flap, tongue base reduction, etc.). Patients who
completed the 6-month follow-up achieved an AHI reduction of 61 ± 24% compared
with baseline. Per Sher criteria (AHI < 20 with at least 50% reduction), 68% were
deemed responders. The four patients, who had UPPP and missed the 6 month visit,
a success rate of 63% was observed. The authors reported a statistically significant
reduction in ODI, apnea index, hypopnea index, and minimal SpO
2
nadir from
baseline to 6 months. Patient-reported outcome measures (ESS and FOSQ) com-
pared with baseline and further improved at the 6-month visit. Stimulation-related
morbidity was low. Therapy adherence was high after 6 months. The authors
concluded that this multicenter study further strengthened the evidence that upper
airway stimulation can be “successfully transferred from the previous controlled
setting (STAR TRIAL) into routine clinical practice” (Heiser et al. 2017).
Tucker Woodson et al. conducted a 5-year outcome from a multicenter, prospec-
tive cohort study of patients with OSA treated with upper airway stimulation (UAS)
via a unilateral hypoglossal nerve implant. From a cohort of 126 patients, 97 com-
pleted the protocol and 71 consented to a polysomnogram. Those having CPAP
failure with moderate to severe OSA, body mass index <32 kg/m (Weaver et al.
2004), and no unfavorable collapse were enrolled in the phase 3 study. Significant
improvements were noted in sleepiness levels, as assessed by the Epworth sleepiness
scale, with scores returning to normal ranges for 33% to 78% of participants.
Similarly, there were positive changes in the quality of life, with scores improving
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from 15% to 67% of their initial values. The rate of positive response in terms of AHI
(apnea-hypopnea index) improvement, defined as AHI less than 20/h and a reduction
of more than 50%, was 75% among the study participants (n = 71). When the last
observation carried forward analysis was used, the responder rate at the 5-year mark
was 63%. Six percent of the patients experienced serious adverse events related to
the device. Results support that in a select group of participants
, upper airway
stimulation therapy can provide improvement in objective and quality-of-life mea-
sures across 5 years (Woodson et al.
2018).
194 A. Khan and M. Hunasikatti
12.7.1 Drug-Induced Sleep Endoscopy (DISE)
Drug-induced sleep endoscopy is an evaluation technique that requires
nasoendoscopic examination of the upper airway under conditions of spontaneous
ventilation and pharmacologic unconscious sedation. Since the recognition of OSA
as a condition that can present with multiple levels of collapse, increased interest has
also developed in using DISE to facilitate the appropriate selection of the best
surgical procedures and maximize the success rate. DISE has been recommended
as a patient selection tool for upper airway stimulation (UAS) due to its ability to
select patients with an increased probability of therapeutic success. DISE is also used
for prescribing mandibular advancement devices and positional therapy. However,
administration techniques vary worldwide partly because it is hard to mimic natural
sleep and there is no best way at present to perform DISE despite many classification
systems.
DISE is typically indicated for children with persistent OSA after tonsillectomy,
those with OSA without tonsillar hypertrophy, children with risk factors
predisposing them to multiple sites of obstruction, or when sleep-state-dependent
laryngomalacia is suspected.
Many different scoring systems have been used to report both adult and pediatric
DISE findings, but none is universally accepted (Wilcox et al. 2017).
12.7.1.1 Scoring Systems for Adults
VOTE (Kezirian
2011): The areas of assessment include the velum, oropharynx,
tongue base, and epiglottis, commonly referred to as VOTE. A grading scale ranging
from 0 to 2 is utilized to evaluate the extent of obstruction: 0 indicating no
obstruction, 1 indicating partial obstruction, and 2 indicating total obstruction.
Furthermore, it is valuable to characterize the pattern of collapse, which can be
classified as lateral, anterior-posterior, or concentric.
NOHL (Vicini 2012): NOHL is focused on four anatomical zones: nose, oro-
pharynx, hypopharynx, and larynx. The severity of obstruction was categorized in
conjunction with the Müller maneuver grading system. Grade 1 is an obstruction
between 0% and 25% airway collapse (no collapse during Müller maneuver). Grade
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2 is an obstruction between 25% and 75% airway collapse. Grade 3 is an obstruction
between 50% and 75% airway collapse. Grade 4 is obstruction greater than 75%
airway collapse (total pharyngeal wall collapse during Müller maneuver).
12 Advances in the Surgical Treatments for Snoring and Obstructive Sleep Apnea 195
12.7.1.2 Scoring System for Children
Six different scori
ng systems (VOTE, SERS, Chan, Bachar, Fishman, Boudewyns)
have been used to report pediatric DISE findings. Unlike the adult scoring systems,
obstruction at the nasopharynx (including adenoids) and supraglottis are commonly
incorporated into these scales.
VOTE (velum, oropharynx, tongue base, and epiglottis): Although this scoring
system is frequently used, it excludes the evaluation of the nasopharynx and
supraglottis.
SERS (sleep endoscopy rating scale): Bachar provides similar information but
incorporates an overall severity score for upper airway obstruction. There are no
published reproducible results for the rating system.
CHAN: Chan and VOTE scoring system evaluate each obstruction level
individually.
Boudewyns: This classification system includes six sites (adenoids, tonsils,
tongue base, palate, epiglottis, laryngomalacia) characterized as fixed or dynamic.
Fishman: This grading system evaluates five sites (nasal, nasopharynx, lateral
walls, tongue base, and supraglottis.
Kezirian reports insights from drug-i nduced sleep endoscopy in nonresponders to
pharyngeal surgery for OSA. This retrospective cohort study of 33 subjects included
consecutive subjects who were nonresponders to previous palate surgery (and
tonsillectomy, whether performed concurrently or not) to treat OSA, and who
underwent DISE. DISE findings were summarized with three analyses: Analysis-1
was a global dichotomous (yes/no) assessment of obstruction at the level of palate/
velum and hypopharynx, Analysis II for the degree of palatal and hypopharyngeal
obstruction and Analysis III evaluated specific structures with a determination of
which structure at the level of palate and hypopharynx was the primary factor in
airway obstruction and also a dichotomous evaluation of whether each of the
individual structures contributed to airway obstruction structures were grouped as
those at the level of the palate (velum/soft palate, tonsils when present) and hypo-
pharynx (oropharyngeal lateral walls, tongue, and epiglottis). Additional evaluation
of mouth opening was recorded (degree of opening <1 cm between maxillary and
mandibular incisors, mild (1–2 cm), moderate (2 – 3 cm), and severe (>3 cm). Over
half of the subjects had PSG. During DISE, the majority of subjects demonstrated
global obstruction (Analysis I) in the palatal region and almost all subjects demon-
strated hypopharyngeal obstruction, largely severe (>75%) obstruction (Analyses I
and II). Subjects with residual palatal obstruction were older and trended toward
higher BMI than those without. There was a notable diversity of specific structures
that contributed to airway obstruction during DISE (Analysis III). These were not
systematically associated with previous hypopharyngeal procedures overall or with
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specific procedures. Tongue contribution of obstruction was common. Like those
without previous OSA Surgery, a diversity of factors may contribute to residual
upper airway obstructions in surgical non-responders. The author concludes that
“residual upper airway obstruction in OSA surgery non-responders likely occurs due
to multiple mechanisms and evaluation techniques like DISE may enhance the
understanding of these mechanisms.” The authors also observed that
oropharyngeal
lateral wall collapse was associated with poorer outcomes after secondary surgery
and may explain a portion of nonresponders to both primary and secondary surgery
(Kezirian
2011).
196 A. Khan and M. Hunasikatti
12.8 Trachesotomy
Tracheostomy is the only definitive therapy and most invasive of all treatments of
OSA as it bypasses the upper airway. The definitive nature of the tracheostomy
procedure, the appearance following the establishment of tracheotomy, and the
change in the ability to vocalize results in significant quality of life/psychosocial
impact for the individual. However, the procedure does result in a decrease in AHI
and improves ESS when compared to untreated OSA cohorts. As many effective
therapies are available at this time, the tracheostomy procedure should be reserved
only as a last resort for morbidly obese patients with concurrent obesity
hypoventilation syndrome, patients with significant craniofacial anomalies, and
OSA patients who have failed or are intolerant of other nonsurgical and surgical
treatments.
12.8.1 Tracheostomy for Adults
Camacho et al. published a systematic review and meta-analysis on tracheostomy as
a treatment for adult obstructive sleep apnea. They reviewed outcomes for
polysomnography, sleepiness, and mortality in patients undergoing tracheostomy
to treat adult obstructive sleep apnea (OSA). Using retrospective review, they
identified 18 relevant studies that were primarily case series. Post-tracheostomy AI
(apnea index) improved from 73.0 ± 27.1 to 0.2 ± 1.2/h and an AI mean difference
of -83.47. The mean AHI decreased from 92.0 ± 34.8 to 17.3 ± 20.5/h and an AHI
mean difference of -79.82 compared with preoper ative status was observed. Post-
surgically, central apneas developed; however, the central AI demonstrated near
normalization to a mean of 2.1 ± 3.5/h after 14 weeks. ODI decreased from
78.2 ± 25.8/h to 20.8 ± 25.5/h. Four studies demonstrated a statistically significant
improvement in subjective sleepiness post-tracheostomy. Postoperative statistically
significant overall and cardiovascular mortality reductions compared with untreated
historical cohorts weres reported (Camacho et al.
2014).
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12 Advances in the Surgical Treatments for Snoring and Obstructive Sleep Apnea 197
12.8.2 Tracheostomy for Pediatric OSA
In children, tracheostomy is infrequently performed for the treatment of obstructive
sleep apnea (OSA). Typically, patients in need of this procedure have an underlying
syndromic condition that leads to the obstruction of the upper airway.
Rizzi et al. examined a group of 29 children below 18 years old, who received
surgical treatment tracheostomy due to the presence of severe obstructive sleep
apnea (OSA) during the period of January 1, 2010 to December 31, 2015. Of
29 patients, 13 had craniofacial abnormalities, 10 had a neurologic disorder with
hypotonia or neuromuscular dysfunction, and 5 had a diagnosis of laryngomalacia
on a fiberoptic exam. The mean follow-up was 30.6 months. All patients were
admitted to PICU with a mean stay of 23.2 days. Most children who undergo
tracheostomy for OSA will remain dependent at 24 months (Rizzi et al. 2017).
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Chapter 13
Impact of REM Sleep on Sleep Disorders:
Current Perspectives
Ahmed S. BaHammam, Mahadevappa Hunasikatti,
and Seithikurippu R. Pandi-Perumal
Abstract Sleep is a complex process characterized by different stages, including
rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Through-
out the night, the body cycles through these stages, with REM sleep episodes
increasing in duration. REM sleep is associated with active dreaming, while the
body experiences muscle atonia and impaired breathing. Research on REM sleep
continues to unravel its mysteries. The regulation of sleep cycles is influenced by the
circadian rhythm and various brain regions. Cholinergic and glutamatergic activities
in specific areas of the brain contribute to the occurrence of REM sleep. Parameters
such as REM latency and REM density are used to measure REM sleep and have
been linked to sleep deprivation, depression, and respiratory abnormalities.
REM-predominant obstructive sleep apnea (OSA) is a condition where apneas and
hypopneas occur mainly during REM sleep periods. It is more common in younger
individuals, women, and patients with mild or moderate OSA. Treatment with
positive airway pressure therapy has shown improvements in functional outcomes
for patients with REM OSA. REM sleep behavior disorder (RBD) is a parasomnia
characterized by dream-enacting behaviors during REM sleep without muscle
atonia. It can be idiopathic or comorbid with neurodegenerative disorders. RBD
has a higher prevalence in males and can lead to sleep-related injuries. Psychiatric
disorders such as major depressive disorder (MDD) and schizophrenia affect sleep
architecture. MDD is associated with disrupted sleep parameters, including
A. S. BaHammam
The University Sleep Disorders Center, Department of Medicine, College of Medicine, King
Saud University, Riyadh, Saudi Arabia
King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
M. Hunasikatti (
✉)
Division of Respiratory, Sleep and Anesthesiology (DSRA), OHT1, Food and Drug
Administration (FDA), Silver Spring, MD, USA
S. R. Pandi-Perumal
Somnogen Canada Inc., College Street, Toronto, ON, Canada
Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences,
Saveetha University, Chennai, Tamil Nadu, India
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
A. S. BaHammam, M. Hunasikatti (eds.), Sleep Apnea Frontiers, Progress in Sleep
Research,
https://doi.org/10.1007/978-981-99-7901-1_13
201
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