Description
This article will primarily focus on FDA-approved neuromodulatory interventions aimed directly at improving sleep/wake disorders. Device therapy is often preferred over the pharmacologic model, given established adverse systemic events with pharmaceutical agents. Rectification or minimization of many clinical conditions or maladies will, in turn, likely enhance the quality and quantity of restorative sleep and may improve, secondarily, overall quality of life.
Within the general field of sleep medicine, there are some 80 formally recognized sleep/wake disorders (01). These fall within such broad categories as:
| • Insomnia
• Sleep-related breathing disorders (obstructive sleep apnea, central sleep apnea, obesity hypoventilation syndrome)
• Circadian rhythm sleep-wake disorders
• Parasomnias
• Sleep-related movement disorders (restless legs syndrome, Willis-Ekbom disease)
• Sleep-related medical and neurologic disorders |
Within the sleep related breathing disorders, there are the obstructive sleep apnea syndromes and the central sleep apnea syndromes.
Each of these will be reviewed as they are the particular disorders targeted with the currently approved device therapies.
Indications
Obstructive sleep apnea. In April 2014, hypoglossal nerve stimulation (HNS) was approved for the management of moderate to severe obstructive sleep apnea as second line therapy. Intake criteria typically include a subset of candidates, greater than 18 years of age, who demonstrate an Apnea-Hypopnea Index (AHI) of 15 minimal to 65 maximal scorable events per hour with at least 15 events per hour occurring in non-REM sleep based on in-laboratory polysomnography. Central and mixed apneas are not to comprise greater than 25% of the total AHI. Further, there is to be documented failure or intolerance to other forms of positive airway pressure applications (eg, CPAP, APAP, ASV, BiPAP). PAP failure is defined as inability to use PAP greater than 4 hours per night for greater than 5 nights per week or unwillingness to use PAP despite compliance attempts. Obesity criteria must be such that the body-mass index is less than or equal to 32 kg/m2. Seriously obese patients lean toward complete concentric collapse (CCC) oropharyngeally, which does not respond satisfactorily to unilateral upper airway stimulation/hypoglossal nerve stimulation. Apnea-hypopnea index predominance of hypopneas exists when summing the apneas and hypopneas (30). In the methodology toward study of upper airway stimulation, other exclusion criteria included neuromuscular disease, hypoglossal nerve palsy, severe restrictive or obstructive pulmonary disease, moderate-to-severe pulmonary arterial hypertension, severe valvular heart disease, advanced heart failure, recent myocardial infarction, severe cardiac arrhythmias, active psychiatric disease, uncontrolled hypertension, or coexisting nonrespiratory sleep disorders that would confound functional sleep assessment (42).
A portion of the diagnostic work-up toward establishing optimal patient selection is drug induced sedation endoscopy. This entails the use of mild sedation in preparation for nasoendoscopy to evaluate the nature of the airway collapse. If the collapse pattern is complete concentric collapse (rather than anteroposterior or laterolateral), the patient is deemed NOT to be an ideal candidate for hypoglossal nerve stimulation.
Baptista and colleagues deem hypoglossal nerve stimulation a personalized, adjustable medical device subject to titration toward effectiveness, with the advantage of the patient playing an active role in their own management (05). The American Thoracic Society states that the nerve stimulation “gently nudges” the tongue moving it forward. Upper airway stimulation is deemed an effective treatment in a select population with high patient satisfaction and low adverse events (03; 24). Early acceptance to hypoglossal nerve stimulation is excellent (92.4% greater than 4 hours on greater than 70% of nights), which supersedes PAP compliance values (24). Van Daele and colleagues conclude that complications with upper airway stimulation, a long term surgical option, were less than with obstructive sleep apnea surgery (43). It was also noted that elderly patients, especially those with a lower body mass index despite associated comorbidities, faired very well with upper airway stimulation.
One reported understanding of the pathogenesis is that, over time, there is a fall in genioglossal electromyography activity (innervated by the hypoglossal nerve [CN XII]), the motor nerve to the tongue. This decrement can result in closure of a vulnerable region of the oropharynx, producing the obstructive apnea. Activation by upper airway stimulation reopens the airway. Beyond the genioglossus muscle as a dilator, the tensor palatini also stiffens the upper airway by having tonic activity throughout inspiration and expiration. Patency of the airway is taxed by retrognathia and/or excessive loading from soft or fatty tissue (32). Of note, factors other than airway closure by hypotonia will influence the frequency of respiratory events and severity of obstructive sleep apnea/hypoxemic burden: arousal threshold, loop gain, and muscle responsiveness hold an important role and may be uninvolved via hypoglossal nerve stimulation (21).
The hypoglossal nerve stimulation (HNS) system consists of a surgically implanted neurostimulator connected to a unilateral stimulation lead in addition to 2 respiration-sensing leads. The sensing leads are tunneled subcutaneously in order to monitor changes in thoracic bioimpedance. A software algorithm helps synchronize the mild stimulation to the pattern of nocturnal respiration. The stimulation lead is placed on the main trunk of the XII nerve distal to branches innervating the tongue’s retractor muscles. It is important to stimulate the tongue protruders (ie, dilators), namely, the genioglossus muscle and the geniohyoid muscle (rather than the tongue retractors) and the hyoglossus and the styloglossus muscles. The final lead cuff placement is determined by intraoperative response to the actual upper airway stimulation. This involves depolarization, generation of action potential and, in turn, excitation of the tongue protruders, which renders the opening of the upper airway, thus, overcoming respiratory resistance and the tendency toward apnea and hypopnea and respiratory event-related arousals. This stimulation trial, during the operative procedure, is visualized using fluoroscopy. If suitable, the lead is then definitively connected, deep to the platysma muscle in the neck, to the actual neurostimulator, which is carefully implanted into the ipsilateral infraclavicular subcutaneous pocket (45). Augostini and colleagues provide impressive details concerning the actual implantation technique, including instructive radiographs (04).
Fleury Curado and colleagues noted that even after controlling for mechanical factors that compromise airway patency, a loss of compensatory neuromuscular responses played a pivotal role in the pathogenesis of airway obstruction during sleep (16). The disturbances are under lingual and pharyngeal neuromotor control. Electrical stimulation can be directed at genioglossus (via stimulation of the proximal trunk and medial branch of the CNXII; lingual coactivation synergistically “stiffens” structures). Stimulation of the veli tensor palatini firmed up the soft palate.
Regarding durability, Soose and colleagues ascertained that hypoglossal nerve stimulation therapy can provide significant improvement in important sleep-related quality-of-life outcome measures and that the effect is maintained across at least a 2-year follow-up period (40). Yu and Thaler declared “CNXII nerve stimulation has shown success greater than 80%. A high majority of patients prefer it over CPAP” (46).
A promising feature of hypoglossal nerve stimulation is the longitudinal care model that could be provided through strict patient follow-up and device titration. The possibility to modulate hypoglossal nerve stimulation parameters lends to customized obstructive sleep apnea management – termed “precision medicine” – whereby the personalized component involves the patient themselves playing an active role.
Future directions may include bilateral hypoglossal nerve stimulation, improved stimulation timing schemes, or more precise (ie, concerted spatio-temporal interplay of multiple lingual muscles) muscular activation for improved airway patency (48).
To detail, a device with the CE mark dating March 2019 and an approval in Europe involves bilateral hypoglossal nerve stimulation with minimally invasive implanted components and a simple stimulation algorithm (14). There are no leads (connective wires) in that the neurostimulator is dissociated from its power source. Three components are involved: 1) implantable stimulator (1 hour procedure; general anesthesia), 2) activation chip, and 3) disposable (single use) patch. The symmetric and uniquely exclusionary protrusion of the tongue may allow approval for complete concentric collapse as well. It is MR conditional (14).
Central sleep apnea. Addressing another sleep-related breathing disorder, central sleep apnea, a bioelectric device has been approved as well (approved October 2017). The device is a phrenic nerve stimulator for gain at diaphragmatic faradizing and pacing (17).
Electrophrenic respiration entails the surgical implantation of a transvenous electrical stimulator. It is placed unilaterally along an intact phrenic nerve with resulting physiological contraction of both hemidiaphragms. Ponikowski and colleagues studied this extensively (36). The primary endpoint regarding efficacy studies was the reduction of apnea-hypopnea index (02).
The medical indications toward transvenous phrenic nerve stimulation include moderate to severe central sleep apnea in adult patients. Conditions associated with central sleep apnea could include amyotrophic lateral sclerosis, multiple sclerosis, polio, brainstem infarction, basilar meningitis, and upper cervical spine injury as well as heart failure, opioid ingestion, and high-altitude exposure (28).
Polysomnography reveals elevation of the central apnea index. Further, Cheyne-Stokes respirations may be seen. This reflects the hypersensitivity of the breathing center with increased loop gain. This is associated with heart failure and prolonged circulatory transit time. Ejection fraction is reduced.
The components include a battery-powered pulse generator, system programmer tablet, and programming wand.
Costanzo and colleagues analyzed whether the use of phrenic nerve stimulation to treat central sleep apnea in patients with central sleep apnea and heart failure was associated with changes in heart failure-specific metrics. They concluded, at the 12-month mark of the pilot study, that findings included: (1) significant - and maintained - reductions in the apnea hypopnea index, mixed apnea index, central apnea index and 4% oxygen desaturation index; (2) improvement in REM sleep and sleep efficiency; (3) continued alleviation of symptoms; and (4) low adverse side effects (11). Further, Fox and colleagues documented the beneficial effects of long-term peripheral nerve stimulation, with no new safety concerns sustained at 36 months (18). Also, in the pivotal trial concerning 5-year safety and efficacy outcomes, Costanzo and colleagues established that peripheral nerve stimulation improves central sleep apnea, sleep architecture, and daytime sleepiness (10).
Ding depicts electrographically the impressively favorable response from the effects of peripheral nerve stimulation when comparing therapy off to therapy on (13). An important contribution from Oldenburg and colleagues centers around transvenous phrenic nerve stimulation producing meaningful improvements in–not just apnea hypopnea index–but also in the nocturnal hypoxemic burden (T90), defined as the minutes of sleep with oxygen saturation less than 90% (35). The T90 is reported as a revealing biometric index.
Contraindications
Obstructive sleep apnea. Hypoglossal nerve stimulation is contraindicated in mild (as opposed to moderate-severe) obstructive sleep apnea or in patients with morbid obesity or in patients with, on drug-induced sedation endoscopy, evidence of complete concentric collapse. Other exclusion criteria include, based on data from the STAR (Stimulation Therapy for Apnea Reduction) trials: prior upper airway surgery; markedly enlarged tonsils; uncontrolled nasal obstruction; severe retrognathia (or other craniofacial abnormality issue); greater than 5% central apneic events; pregnancy or plans toward pregnancy; MRI plans; incompletely treated sleep disorder other than obstructive sleep apnea; or major disorder of the pulmonary, cardiac, renal, or nervous systems.
Central sleep apnea. Phrenic nerve stimulation is contraindicated in the setting of a nonfunctional phrenic nerve or nonfunctional diaphragm. Apnea of a central cause must stem from a lesion higher than C2 because the phrenic nerve originates, anatomically, from the anterior horns of cervical spinal cord levels C3-5 (38). Importantly, Nayak and colleagues share that data are lacking regarding device-device interaction (transvenous phrenic nerve stimulation and cardio-vascular implantable electronic device) and that a detailed interaction protocol should be followed to minimize the incidence of interaction; they conclude that there was no evidence of impact on safety or effectiveness during concomitant usage (34).
Outcomes
Obstructive sleep apnea. The bioelectronics approach to moderate to severe obstructive sleep apnea, by upper airway stimulation via hypoglossal nerve stimulation is promising (06). The modality is promoted as safe and effective. The increased tonus of the tongue and other soft tissues prevents collapse during slumber such that airflow and breathing are stabilized, SaO2 levels improve or normalize and sleep continues uninterrupted--without arousals. There is high therapy adherence. Durable long-term results are noted. The apnea-hypopnea index drops substantially (50% to 70%) and snoring remits and bed partners are more content. Daytime performance is enhanced. Proper management of obstructive sleep apnea can lead to a reduction in the risk of otherwise devastating effects on heart and brain health. Treatment can possibly obviate the eventuality of heart failure, hypertension, coronary artery disease, stroke, neurocognitive impairment, diabetes, depression, accidents (occupational or motor vehicle), neuroendocrine disturbances, performance deficits, personality alterations, and reduction in quality of life (08).
Central sleep apnea. Diaphragmatic pacing by phrenic nerve stimulation has resulted in a significant lowering of apnea-hypopnea index along with improved sleep efficiency, percentage REM sleep, remitted arousals, enhanced oxygenation (36), and clinically meaningful improvement in general and mental health (well-being, per patient global assessment) along with enhanced social functioning (25). Fudim and colleagues publish that transvenous phrenic nerve stimulation also improved quality of life, sleep quality, and ventricular function (19). Patient compliance is not at issue because the apparatus is indwelling. There is no mask involved. The improvement and the high therapeutic acceptance was noted in both PAP-treated and PAP-naïve patients; they indicated that they would undergo the implant again, underscoring positive feedback (37). Transvenous phrenic nerve stimulation was perceived as a viable therapy across a broad spectrum of central sleep apnea patients.
Adverse effects
Obstructive sleep apnea. Adverse events of hypoglossal nerve stimulation drug-induced sedation endoscopy include, short-term, the surgical risks of wound infections, hematomas, and nerve palsy as well as transitory subjective tongue weakness. Hardware removal is an option. Longer-term risks include discomfort with ongoing electrical stimulation (note: the parameters are modifiable per patient preference), soft tissue abrasions (manageable with use of a plastic dental guard), and dry mouth. Drug-induced sedation endoscopy carries the inherent risks of hypoventilation, oxygen desaturation, and prolonged recovery due to sedation from either administration of midazolam or propofol. Battery life is 11 years, depending on duty cycle and other stimulation settings. It was stressed in regard to, surgically, accessing and rendering stimulation only to the tongue protruders, not to the tongue retractors. A topographical map, established from cadavers, of the hypoglossal nerve terminal motor points was created and could thus provide a valid framework for the optimization of the neurostimulation techniques (07).
Central sleep apnea. Phrenic nerve stimulator implantation involves the usual risks of surgery, namely infection or hemorrhage. The purported advantage over positive airway pressure applications is based on the physiology. With stimulation of the diaphragm, there is negative intrathoracic pressure, which is more natural than would be the case with positive airway pressure. Airflow is augmented such that the cyclical periodic breathing is overcome, and blood gas alterations are avoided. This, in turn, minimizes the harsh hemodynamic effects in known cardiac patients (38).
Special considerations
Obstructive sleep apnea. To summarize, obstructive sleep apnea is characterized by, commonly, nocturnal breathing interruptions (apneas and hypopneas), snoring, gasping, or choking with associated arousals. This leads to nonrestorative sleep and consequent daytime fatigue or sleepiness and dysfunction. Positive airway pressure is often prescribed for patients with obstructive sleep apnea. The device is cumbersome. Compliance rates are only approximately 40%. Weight loss is always within the formula for remission. Surgical approaches are not popular; these could include adenotonsillectomy, uvulopalatopharyngoplasty, radiofrequency ablation for resection of the tongue base, maxillomandibular advancement, and transoral robotic surgery.
Strohl and colleagues advocate toward a center-based approach for stimulation therapy, whereby there is a case management plan and a system of designated leadership rolls (41). They are also quoted as stating: “Economic considerations are important. In the United States, the acknowledged willingness-to-pay threshold is $50,000 - $100,000/QALY. Modeling on this threshold, the relative costs and benefits suggest that upper airway stimulation could be a cost-effective therapy in this healthcare system.”
Selective upper airway stimulation is established as leading toward significant reductions of apnea hypopnea index, oxygen desaturation index, and Epworth sleepiness score, including in older patients. That is, advanced age seems not to be a limiting factor for treatment outcomes of selective upper airway stimulation (50).
In February 2021, the FDA approved and authorized a neurostimulator device that electrically excites the genioglossus musculature to enhance tonus (44). The mouthpiece is to be worn daily for 20 minutes for 6 weeks, then once per week for 20 minutes thereafter, as maintenance. Snoring is overcome for those with mild obstructive sleep apnea defined as less than 15 on the apnea hypopnea index. The daytime intervention bears nighttime results, with reduced partial airway collapse and reduced audible snoring; this improves relationships. The unique modality is simple and comfortable, overall.
Central sleep apnea. To summarize, central sleep apnea is a devastating health problem found predominantly in males. It is uniquely associated with heart failure. Contributing factors can include opioid exposure or brainstem insults. Central sleep apnea, pathogenetically, involves the interruption of an otherwise properly controlled brainstem respiratory drive. The respiratory control system operates via a negative feedback loop with tightly regulated oxygen and carbon dioxide levels during human activity, aging, and disease. Respirations will cease if PaCO2 levels fall below the “apnea threshold.” This is the problem for patients with heart failure. They have hyperventilation, circulatory delay, and cerebrovascular reactivity, which destabilize normal breathing, leading to Hunter-Cheyne-Stokes respirations, a crescendo-decrescendo pattern of respiration identifiable in polysomnography. With Cheyne-Stokes respirations (CSR), given the impaired respiratory drive system, there is onset of alternating hyperventilation and hypoventilation. The overshoot or inaccuracy of the breathing pattern begets apnea, hypoxia, re-oxygenation, and arousal of the patient. This creates deleterious consequences including: sympathetic/autonomically excitatory nervous system activation, oxidative stress, adrenohumoral damage, systemic inflammation, and vascular endothelial dysfunction. These repetitive injurious phenomena may elicit tachycardia, vasoconstriction, sodium retention, or renin-angiotensin-aldosterone activation with increased pre- and post-load on the already compromised heart, inducing electrical, contractile, and structural cardiac remodeling with myocardial ischemia with coronary arrhythmogenesis.
Patients with heart failure and Cheyne-Stokes respirations or central sleep apnea present with insomnia and fatigue along with excessive daytime sleepiness. They tend to report frequent awakenings, poor quality sleep, shortness of breath, paroxysmal nocturnal dyspnea and nocturia. Holfinger and colleagues beckon that cardiology services recognize that treatment of sleep apnea is an important but easily overlooked aspect of care in the heart failure patient (22). Patients may have lowered left ventricular ejection fraction as well as waking hypocarbia (PaCO2 less than 38 mm Hg), elevated beta-natriuretic peptide levels, and elevated overnight urinary catecholamine levels. Nocturnal cardiac arrhythmias are noted on polysomnography. In patients with congestive heart failure, continuous positive airway pressure adherence is problematic and automatic servo-ventilation is not indicated based on an already failing heart and lowered left ventricular ejection.
Regarding restless legs syndrome/Willis-Ekbom disease – a commonly recognized malady in sleep medicine – there are forms of neurotechnology aimed at treating the condition, which is known to fractionate sleep architecture given recurrent arousals. The devices are generally aimed at the stimulation, externally, of sensory nerves in order to diminish the urge of restless legs syndrome or for chronic pain in general. Vibrations are induced that gradually ramp down and stop. The later versions, approved by the FDA as level 2 medical devices, deliver approximately 3 times the power of a standard transcutaneous electrical nerve stimulator device. Diminishing pain improves sleep. In June 2020 the FDA granted breakthrough device designation for NTX100 neuromodulation therapy designed for the treatment of adults with primary moderate-severe restless legs syndrome. This approach could obviate the need to prescribe dopaminergic agents that are known to be fraught with high-risk side effects such as “augmentation.” This wearable is touted to target specific peripheral nerve fibers in a manner that is comfortable to wear to sleep. Because restless legs syndrome is regarded as the second most common sleep disorder, this nonpharmacologic approach could impact a large population still suffering from refractory symptoms of painful sensations of tingling combined with the urge to move limbs for transient relief.
Another form of neurostimulation is the time-honored vagus nerve stimulator. This device is approved for treatment of medically refractory epilepsy and also regarding management of recalcitrant depression. Lessening of seizure burden and risk of same, with associated assuaging of fret, improves sleep hygiene. A novel subtype of vagus nerve stimulator, aimed at improving sleep, is that of transcutaneous auricular vagus nerve stimulator. Zhao, in exploring the amplitudes of low frequency fluctuations of this form (transcutaneous auricular vagus nerve stimulator) of neuromodulation, surmised that it was effective for primary insomnia (49).
As is commonly known, insomnia is a pervasive problem. It has a large negative impact on function, health, and quality of life, resulting in a major public health burden. It is the “springboard” toward serious neuropsychiatric maladies including depression, anxiety, suicide, and substance abuse. Typically, in broad terms, within the field of sleep medicine there are 2 arms toward clinically addressing insomnia. There is, traditionally, psychopharmacotherapy and there is cognitive behavioral therapy for insomnia. Neither modality is deemed near ideal. The medicines, for instance, are fraught with unfavorable side effects; habituation, tolerance, psychological issues, and expense. So comes forth repetitive transcranial magnetic neurostimulation. This is a controversial physical method but is certainly gaining ground for the above reasons and suspected efficacy as well. Further evidence-based research for refinement is indicated.
Repetitive transcranial magnetic neurostimulation is thought to – by induction of electrical currents – activate neural elements in the cortex and subcortical white matter. Pulse sequences may range from 1 Hz to 20 Hz. Reportedly, therapeutic utility has been recognized in parkinsonism, dystonia, schizophrenia, depression, and others. The theory is that the impulses inhibit the hyperarousal state of the cerebral cortex, affecting metabolic activity and sleep-related hormones and neurotransmitters, thus promoting hippocampal neurogenesis. Song and colleagues targeted, with low frequency repetitive transcranial magnetic neurostimulation, the right posterior parietal cortex and noted significant positive effects on the treatment of primary insomnia (39). Huang and associates corroborated, with low frequency 1 Hz repetitive transcranial magnetic neurostimulation, and found it effective for both insomnia symptoms and for generalized anxiety disorder (23). Feng and colleagues deduced that the application of bilateral low frequency repetitive transcranial magnetic neurostimulation over the dorsolateral prefrontal cortex significantly improved primary insomnia by supposedly increasing the levels of brain-derived neurotropic factor and of gamma-aminobutyric acid along with the reduction of cortical excitability (15). Nardone and associates espoused that both low frequency and high frequency repetitive transcranial magnetic neurostimulation, when applied over either the primary motor cortex or the supplementary motor cortex, rendered transient beneficial effects in patients with restless legs syndrome (33). Jiang and colleagues explored the network meta-analysis for sleep efficiency and graded certain modalities in the order of: orexin receptor antagonists, GABAergics > CBT-I > acupuncture > repetitive transcranial magnetic neurostimulation (26). Stage 3 sleep and REM sleep cycling were improved, as were the indices of the hypothalamic pituitary axis, as purported by Jiang and associates (27). A robust placebo response was noted.
In another modus of neurostimulation, Zabrecky and colleagues investigated the efficacy of vibroacoustic stimulation and found that it improves sleep in patients with insomnia (47). The target was delta waves. They utilized the Theracoustic Vibracoustic Wellness System, which is claimed to lower brainwaves to deeply meditative states. Music developed from electroencephalographic patterns, similarly, was found to render substantial improvement in sleep patterns amongst patients suffering from insomnia.
Within the greater realm of neurostimulation there is deep brain stimulation, which has been utilized, medically, in a broad sphere of conditions.
For example, deep brain stimulation has been utilized in parkinsonism (ventral subthalamic nucleus implantation) with – in the sphere of nonmotor benefits – enhanced mood, improved sleep, and lessened apathy. It has been employed, successfully, in certain psychiatric disorders such as obsessive-compulsive disorder, PTSD (basolateral nucleus of amygdala), and depression with, expectantly, consequent improvement in sleep quality. There are neuroethical considerations with deep brain stimulation in that it has been recognized as changing disposition, emotionality, and behavioral states that play a central role in the conceptions of personality, identity, autonomy, authenticity, agency, and/or self.
There is debate in the field regarding whether nighttime brain stimulation improves slow oscillations of NREM sleep and, thus, improves memory consolidation (20; 31). Ketz and colleagues suggest that augmentation of slow-wave oscillations with closed-loop transcranial alternating current stimulation enhances the consolidation of recent experiences into long-term memory (29). Bueno-López and colleagues failed to reproduce this and, thus, refuted the supposition (09).
Clinical vignette
A 58-year-old man with a past medical history of viral pericarditis with tamponade and, as sequelae, ischemic cardiomyopathy with lowered ejection fraction underwent surgery for a high cervical cord and extramedullary schwannoma. The resection resulted in postoperative complications of Brown-Sequard syndrome and partial paralysis of the diaphragm.
The patient developed nocturnal stereotypic gasping and choking, with associated air hunger and anxiety with arousal. He had extreme daytime sleepiness and grumpiness. Data revealed retromicrognathia, a body mass index of 41 kg/m2, and neck girth of 19 inches, Mallampati score of 4 with ECG manifestation of atrial fibrillation and ABGs showing non-hypercapnic and hypoxemic patterns. Polysomnography revealed shortened sleep latency, lowered sleep efficiency, elevated apnea index (55.5 events per hour) and oxygen desaturation (SpO2 72%) with Cheyne Stokes respiration pattern and no REM sleep nor N3 slow-wave sleep.
Both obstructive sleep apnea and central sleep apnea were noted per polysomnography scored reports, hypnogram, and annotations.
The patient was a valid candidate for hypoglossal nerve stimulation or upper airway stimulation. He was not a valid candidate for phrenic nerve stimulation or diaphragmatic pacing because he had a nonfunctional phrenic nerve and diaphragm as residual factors stemming from his tumor mass and its extirpation.
