Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea
Associate Professor, University of Arizona College of Medicine – Tucson
Dr Saif Mashaqi first obtained his medical degree from the University of Jordan and then moved to the United States where he completed his Internal Medicine Residency and Pulmonary Diseases Fellowship at Marshall University School of Medicine in Huntington, West Virginia. During the fellowship, he had the opportunity to study sleep medicine as an elective module, which sparked his interest in Sleep Medicine. After completing residency and fellowship at Marshall University, he moved to the Cleveland Clinic in Cleveland, Ohio, where he completed sleep medicine and critical care fellowships in 2012. In 2019, he moved to the University of Arizona to pursue sleep medicine research in which his research interests are on upper airway stimulation and gut microbiomes’ impact on obstructive sleep apnea.
How common is Obstructive Sleep Apnea (OSA) and how effectively is it diagnosed?
Jonathan: You mentioned that you have become acquainted with the experiences of patients who have Obstructive Sleep Apnea. Could you perhaps say a few words about how common this condition is? It might be as high as 22% in the male population and as high as 17% in the female population. Also, the impacts are fairly severe, is that right?
Saif: Absolutely. Obstructive Sleep Apnea is a common disease and one of the challenges we face is that there are many undiagnosed cases. We are trying to do as many screenings for Obstructive Sleep Apnea as possible. We now think that the number is increasing to approximately 40-50% in terms of the prevalence of this disease. We estimate that there is an increasing number of undiagnosed cases of Obstructive Sleep Apnea, which is one of the challenging areas in sleep medicine when we try to find a good screening tool for the disease because there are many undiagnosed cases out there. Simultaneously, we know the correlation between Obstructive Sleep Apnea and its impact on other chronic diseases like cardiovascular, cerebrovascular, metabolic and neoplastic diseases, which means that we need to do a better job regarding screening.
How do hypoglossal nerve stimulation and CPAP (Continuous Positive Airway Pressure) compare as treatments for Obstructive Sleep Apnea?
Jonathan: The impact of the disease is potentially enormous and perhaps some very large fraction of people are not aware that they have it. The nerve stimulation in this scenario typically relates to the hypoglossal nerve. During my clinical days, I learned to test hypoglossal function by getting patients to wiggle their tongues and after reading around its anatomy, I found out that it is a rather intricate and beautiful piece of biological machinery, right?
Saif: Yes, it is actually a fascinating modality of treatment, and I would like to mention that the gold standard for treating Obstructive Sleep Apnea is CPAP. However, we have been facing over many years that CPAP has been a problem for many patients as they have been struggling with having the face mask over their nose and mouth. Patients have been complaining about using this method, so that urges us to look for alternative options of treatment. From there, new upper airway stimulation and neuromodulation came as a promising alternative way to treat patients. So the whole idea in upper airway stimulation -neuromodulation and hypoglossal nerve stimulation- actually depends on the function of the hypoglossal nerve. The hypoglossal nerve, as we know it, is a pure motor nerve that innervates the tongue and it divides into many branches that supply muscles in the tongue, hypopharynx and palate. If you look at the anatomy of the upper airway in the soft palate and hard palate, the way the hypoglossal nerve innervates this muscle is actually fascinating in a way that the end results are to keep the hypopharynx open and maintain the patency of the hypopharynx. That is actually the idea of using neuromodulation in order to stimulate this nerve and simultaneously stimulate the muscles that will subsequently keep the upper airway open and maintain the patency of the hypopharynx.
What is Obstructive Sleep Apnea and how do CPAP and neurostimulation treat it?
As you see in Figure 1, close to the big red arrows there’s the main trunk of the hypoglossal nerve in yellow. This is divided into several branches that supply two groups of muscles that work in two opposite functions. One group of muscles protrudes the tongue and the other group causes retrusion of the tongue. The goal, in order to help patients with Obstructive Sleep Apnea, is to cause protrusion of the tongue. If you cause a minimal protrusion of the tongue during sleep, it helps these patients by opening the airway.
So just going back a little bit to the pathophysiology of Obstructive Sleep Apnea, what happens in patients with OSA is that their hypopharynx is narrowed and there is a complete collapse during sleep. When you have a complete collapse that’s actually when you have apnea. So we can help these patients by keeping this space open during sleep. That’s what the CPAP does. With the CPAP we provide a continuous column of air that will provide an air stent during sleep and keeps that space open.
With neuromodulation, we stimulate the hypoglossal nerve, which stimulates the protrusion of the tongue by stimulating the genioglossus muscle. So the genioglossus muscle when stimulated will cause protrusion of the tongue which opens the airway. We are focusing mainly on the green area in Figure 1. Stimulating the protrusion fibers of the tongue will cause protrusion of the tongue and it will result in the opening of the airway.
How is the Inspire® device programmed after surgery?
After the device is implanted by the ENT surgeon the next phase is that the patient will be seen by the sleep physician in the clinic. After we check that all the wounds are healthy and there is no problem, we come to the next phase which is the activation of the device. We activate the device with a tablet that we use in the clinic and we turn the device on. Once we do that, we start gradually delivering a very minimal stimulus and we ask the patient to let us know when they start feeling something in the tongue. We start with the lowest amount of volt, so we start with 0.1V, then 0.2V until they start feeling something. When they start feeling something that is gonna be our start point. For example, if they start feeling something at 0.3V that is going to be our start point and from there we increase the intensity of the stimulus until we see the tongue protruded at least by 1/3 beyond the incisors and that is going to be our upper limit. That is going to be the range they will leave the clinic with.
All this procedure is done with the patient being alert, awake and we need to make sure that they don’t have any pain! Of course, they will feel something abnormal and that is expected because even when they start using the CPAP they will take some time to get acclimated to it.
After we have programmed the device and before they leave the clinic, we will give them a remote and instruct them how to use it. With that, they will be able to turn the device on and off and it also allows them to program the device. For example, if they wake up in the middle of the night to drink water or to go to the bathroom they will be able to pause it and it will give them a pause for 10 or 15 minutes. Also, the device will shut down automatically when they wake up in the morning because otherwise if they forget it, they will be protruding the tongue when they go to work, which is not fun. So the device automatically shuts by itself when the patients wake up in the morning and that’s based on programming the device according to your total sleep time.
When they go home, we ask the patients to gradually increase the energy delivered, every 3 days over 2 months until they get to the maximum amount of energy they can tolerate so that they get acclimated. We want them to be able to tolerate the maximum amount of energy that can be delivered through the Inspire® device without any problems. Now of course throughout this course some of them call us and say that they are experiencing pain or discomfort. In that case, we ask them to go back to the previous level of energy and try increasing it again after a few days.
When they get to the maximum level of energy they can tolerate, we do a sleep study and then we finalize the level of energy they can tolerate and set them up with that level of energy.
Can all patients undergo hypoglossal nerve stimulation?
The patient has to go through a long list of inclusion and exclusion criteria for the hypoglossal nerve stimulation surgery. One of the most important things is the severity of sleep apnea, for example, patients who have mild sleep apnea are not good candidates for this procedure, it’s only for patients who have moderate and severe sleep apnea.
Another exclusion criterion unfortunately is patients who are obese, so those with a BMI of more than 32. We know that patients who are obese tend to have more severe obstructive sleep apnea, but unfortunately, they don’t qualify for the Inspire® device or upper airway stimulation. They found that patients with a BMI of more than 32 tend not to respond to upper airway stimulation or neuromodulation and the reason why is because they tend to have more of a complete concentric collapse.
What does that mean? Let’s say that the patient meets the inclusion criteria, i.e. they have moderate or severe sleep apnea and they are thin, let’s say that their BMI is 29. The next step is to send them to the ENT and look at the pattern of their upper airway collapse. The ENT will do an endoscopy, something called a DISE exam -Drug-Induced Sedation Endoscopy- so they simply mimic a state of sleep by infusing the patient with midazolam or propofol and they do an endoscopy to look at how the upper airway collapses when they have sleep apnea. There are two types of collapse, if the collapse comes from all sides we call it complete concentric collapse, in that case, the upper airway stimulation tends to fail. If the collapse comes from the anterior-posterior axis or what we call the palatal axis, the patient tends actually to do well with the hypoglossal nerve stimulator, but the decision is made by the ENT.
So patients with severe obesity usually have complete concentric collapse, which is why they tend not to do well with the hypoglossal nerve stimulator.