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Sleep Disorders

We divide sleep up into different states. There is REM sleep, or rapid eye movement sleep, non-REM sleep. Non-REM sleep is everything apart from REM sleep and non-REM sleep is divided into progressively deeper stages that are reflected by the slowing in the electroencephalogram. We stage sleep with an EEG like a monogram and electrooculogram. The things that are useful to point out here are simply that when you go from awake to drowsy you start to regularize a little bit and slow down. This is sort of what happens towards the end of the lecture as the lights stay down. If you haven’t had enough coffee. Then as you go into a more convincing stage II sleep, things slow further and then delta sleep, what’s called delta sleep or acute non-REM sleep, things slow even more. REM sleep looks remarkable like the waking EEG and there are many features of REM sleep physiologically that are actually very similar to waking sleep apnea, narcolepsy, insomnia, daytime sleepiness.

There are some physiological changes associated with sleep changes. This is muscle sympathetic nerve activity reported in the perineal nerve. This is blood pressure and as you can see, as the subject goes from awake to non-REM sleep the sympathetic activity declines progressively. Blood pressure declines and then in REM you can see this enormous increase in sympathetic activity with wide swings in blood pressure. This is in a normal subject sleep apnea, narcolepsy, insomnia, daytime sleepiness.

Sleep is a very organized behavior. There is a specific pattern of sleep across the night. As you drift off you go into stage I sleep and stage II and then you may spend some period of time in stage III or IV, go back to stage II sleep and then in roughly 90 minutes into that you go into your first episode of REM sleep. That episode is brief. Sometimes as short as five minutes then you go back into non-REM, have some more delta sleep and

Insufficient sleep. Individual sleep need varies. There is no right amount of sleep to get although most people in our society are sleep deprived and should you evaluate the patients with complaints of daytime sleepiness you have to factor that in. Having insufficient sleep doesn’t rule out another sleep disorder in fact insufficient sleep may worsen sleep apnea. So if a patient comes to you and tells you he gets five hours of sleep a night but he is exhausted during the daytime doesn’t necessarily have just insufficient sleep. They may have a coexisting sleep disorder, in fact that sleep disorder may be part of why they have insufficient sleep. By that I mean, patients who have constructed their sleep schedule for a reason - if they are waking up due to sleep apnea or if there is something uncomfortable about their sleep, it may end up shortening their sleep cycle.

Obstructive sleep apnea. The prevalence is high, as we will talk about in a second, and it depends highly on the definition. This may be a minimal prevalence. The prevalence actually in some populations is so high as to make you really question as to whether or not this is a disease or if this is a natural occurrence, a natural aspect of physiology in humans. We have collapsible airways. It’s one of the prices we pay for being able to speak. The consequence of that is that when we go to sleep our airways may collapse. Recognize that one-third of patients with sleep apnea have at least or less than 120% of the ideal body weight. I describe most of my patients as being typical Americans. They are in the range of 120% of their ideal body weight. As the population prevalence of obesity goes up, obesity no longer becomes a discriminant but not every patient with sleep apnea is obese. Think about the tetra of symptoms: excessive snoring, daytime sleepiness, systemic hypertension and obesity. If you have those things you

Concentrate your exam on the upper airway. There is one study that suggests an neck circumference of 17 inches in males is highly correlated with sleep disorder breathing. In particular look for nasal obstruction. Look for an overbite. A lot of the thin patients with sleep apnea have an overbite and physicians don’t tend to note that on an exam but that is a common aspect of upper airway narrowing.

Consequences of sleep apnea: neuropsychological, consequences of sleep deprivation, cardiovascular consequences, and other consequences of hypoxia. Neuropsychological consequences that we consider problems with attention, deficits of working memory. Patients will often complain that

Effective therapies are available for the majority of patients. Many patients with mild sleep apnea do benefit from therapy. There is what I would call an expected dissociation between symptoms and projected measurements in severity, and compliance continues to be an ongoing battle. Effective therapies are available. For sleep apnea we start with the appliances, sleep apnea dental appliances. Surgical therapies are done, I think too frequently, and pharmacologic therapy I think is coming along as an intervention that we use increasingly. Nasal CPAP I still consider the first line of therapy for the vast majority of patients. Many do go to mandibular positioning devices as described which are best used in patients with mild or moderate disease. I think surgery should generally be used to make another therapy, CPAP, more effective or as I call it salvage therapy. Patients who fail either CPAP or dental appliances. Even when you have treated someone with these other treatments, treating the symptoms may be necessary so increasingly there is interest in using stimulant medications in patients with sleep apnea to manage the symptoms, particularly in daytime sleepiness.

All patients should start with behavioral therapies, limiting sedating drugs and alcohol, weight loss and avoiding sleep deprivation. But I will tell you that in my practice I don’t have great success with weight reduction therapy to begin with, but there is substantial evidence in sleep apnea that weight gain is as much a consequence of the disease as it is a cause of the disease and only about one-third of the patients with sleep apnea who lose substantial weight actually have their sleep apnea resolved. So if you have a narrowed upper airway and you have sleep apnea - many of these people have sleep apnea dating from their childhood when you really go back - you change your lifestyle. You aren’t as active. You don't climb the extra flight of stairs, you aren’t going to take the walk in the evening because you are tired all the time. And the consequence of that is that you gain weight. Then the obesity probably exacerbates the sleep apnea and leads to worsening symptoms of sleepiness. Mandibular positioning devices: published reports suggest that these therapies are effective in about 60% of patients. I would say that is optimistic. My experience hasn’t been nearly that good but that’s what in the literature. There are adjustable appliances which now seem to be the preferred therapy. There are a variety of over-the-counter devices that are much cheaper but probably less effective. The problem with the adjustable appliances is that they are more expensive. Construction and fitting are tedious and the long term consequences are still uncertain. By that I mean these devices work by pulling the lower jaw forward while the patient sleeps. The long term effects in terms of creating TMJ problems or occlusion problems really isn’t known at this point.

The advantages of these mandibular positioning devices are: patient acceptance is good and they are portable. The disadvantages are that reimbursement is still questionable in many locations. They are considered dental devices rather than medical devices so medical insurance often won’t cover them. It often takes four to five months for the device to be fitted and adjusted so from the time of diagnosis to the initiation of therapy is often unacceptably long. And you may end up going through this and end up with a device that doesn’t work. Then finally, as I said, long term consequences are unclear. This is what one of these devices looks like. It hooks on upper and lower teeth and uses the upper jaw and maxilla to push the mandible forward during sleep.

CPAP: still the gold standard of therapy. You can’t predict compliance. That’s been shown repeatedly in a variety of areas from hypertension to asthma in sleep apnea. Average use is about five hours a night but most patients with proper adjustment and management will use the device. And a compliance pattern may be established early so you want to get relatively aggressive with the patient to make to sure that they use the device. This is an older machine but the current machines are actually smaller and lighter. As I get on a plane these days it’s not uncommon to see someone carrying a CPAP device. But this is still what the masks tend to look like. It’s not the most aesthetic device in the world. Nobody loves CPAP but they wear it because they like what it does for them. This slide just reports compliance. This is average use, this is over a month. The percentage of patients

The other devices are similar to CPAP but the expiratory pressure is below the inspiratory pressure and the thought was with these devices that they would improve compliance. One study that has been done suggests that it doesn’t improve compliance, (BIPAP) doesn’t improve compliance, but the study really was flawed and subsequent studies have been similarly flawed. By-pak we are actually using more frequently now because as you

Surgical therapies are more effective for snoring than for sleep apnea. I consider it salvage therapy for patients who fail or refuse CPAP and the success of natural or facial surgery is not yet established. The laser assisted uvulaplasty went through a big big vogue, at least in our area a couple of years ago. I think it was termed a laugh because it was so easy for the ENT surgeons to make money on this thing. This is an office procedure in

Uvulopalatopharyngoplasty is the standard ENT operation for sleep apnea. It is described as something like a facelift in the throat. They go in and take out a larger amount of tissue. There are no predictors of success to this procedure. Effectiveness diminishes with time and something to remember is it may reduce subsequent effectiveness of CPAP. So if you are going to send someone for a UPPP recognize that it may preclude

There is a lot of interest in pharmacological therapy for sleep apnea. There is no current treatment that is documented as effective. Protriptyline, fluoxetine - Prozac - has been used in the past but probably aren’t that effective and their side effects limit use. But there is a great potential I think now for the use of other agents for the treatment of sleep apnea.

The causes of daytime sleepiness: depression, sometimes it’s helpful to ask about sleep initiation problems because that helps to distinguish, early morning waking is a characteristic of depression. Frequently there are complaints of disrupted sleep. On a sleep study you can suspect a depression from the REM. Often patient complain of fatigue or tiredness rather than sleepiness. Periodic movement sleep syndrome is a condition in which patients make rhythmic, repetitive muscle movements in their lower extremities. It’s not a cramp. It’s a kicking movement. It looks like an extensor reflex, like a Babinski, actually if you videotape. It is frequently associated with restless legs which is a symptom of a discomfort in the leg, often relieved by moving at sleep onset. Periodic movements may cause difficulties in sleep continuity. Patients wake up at night and can’t get back to sleep, or it may cause daytime sleepiness. The patient or bed partner can be unaware of the leg movements. And this is the thing I want to stress: it’s associated with renal failure. Everybody on dialysis has periodic movements. Pregnancy, iron deficiency - this association may be the same thing. The big point here is that the SSRI’s, the serotonin re-uptake inhibitor drugs - Prozac, Wellbutrin, Zoloft - cause periodic movements, and patients will develop daytime sleepiness and not know what the cause is and frequently the psychiatrist doesn’t know what causes it. There are a variety of

I want to talk some about narcolepsy because there are some exciting things happening here. Daytime sleepiness, cataplexy, sleep paralysis at sleep onset. The sense of being paralyzed at sleep onset. It is often, patients describe, as the inability to move. Or hypnopompic hallucinations, which is beginning to dream actually at onset. Often these are characteristic, kind of frightening images. One really common one is the sensation of something sitting on your chest. These are the text _ symptoms of narcolepsy. You don’t have to have this tetra to have narcolepsy. In fact the only thing you really need is daytime sleepiness, which is why this is a very difficult disease to diagnose now. If you have these other things, it’s extremely likely that

Right now our therapy for narcolepsy is still somewhat limited. It is complicated by the use potential of the major therapies and all have other problems. Amphetamines have problems with over-stimulation, the duration of action often. There are short acting drugs which feeds into the abuse of the drugs. Ritalin has problems with absorption and again with duration of action. The slow-release form of Ritalin is much more erratically absorbed than the conventional preparations. And pemoline, Cylert, is associated with hepatic toxicity which you have to monitor for and occasionally it makes you stop the drug. It’s probably a less effective agent anyway. There is a new drug out now, medimanole, which has weight-promoting properties and seems to be probably the standard, will become the standard therapy for narcolepsy. It’s sites mechanism of action are distinct from the sympathomimetics and interestingly enough, just before the identification of this, the genetic locus of narcolepsy was found, our group in Boston identified with the locus of action of histaminergic cells in the brain activates the histaminergical arousal system.

I’m going to talk very briefly about insomnia. When you approach patients with insomnia you want to distinguish transient and intermittent insomnia, from persistent insomnia. Transient insomnia that is occurring in association with acute stress is quite appropriately treated with pharmacotherapy. Intermittent insomnia may be appropriately treated with pharmacotherapy. Persistent insomnia is much less appropriately treated with pharmacotherapy. These are the patients who tell you they never sleep. These are the ones you shouldn’t be giving the sedatives or hypnotics to.

Treatment of idiopathic insomnia has been … there’s a huge literature about how to approach these patients. Things that are useful to take home as a practicing physician are: you want to clean up their sleep hygiene. You know, the patient who exercises just before going to bed is not going to be able to go to sleep. So if they are going to exercise they need to do it in the morning. The patient who is complaining about difficulty in sleep onset and initiating sleep and walks into your office at 3 o’clock in the afternoon with a big one from Dunkin Donuts has got a problem with caffeine ingestion. So patients like this need to clean up their sleep hygiene before you really do anything else with them. So you want to cut out caffeine intake and really go through their diet with them. You want to make sure they are not exercising too late in the day. You want to make sure that they are not doing things that are 

Circadian disturbances, shift work and what’s called delayed sleep phase syndrome. Delayed sleep syndrome is what I want to concentrate on. It’s a disorder for adolescents. Adolescents manifest it primarily. They find themselves going to bed later and later and getting up later and later. In particular what you want pay attention to is the fact that the adolescent tells you that the adolescent is allowed to find his own cycle. Go to bed 3 get up at noon, he’s not sleeping the rest of the time. Can function fine. If you try to put him on a forced normal light/dark cycle they find that they can’t

Nasal CPAP remains the standard therapy for patients with moderate to severe OSA

Compliance is enhanced by careful follow-up and reinforcement Average use varies but in most series is approximately 5 hrs/night

There may be a bimodal pattern of use with some patients using the device for the full night and others using it for only a few hours/night

Usage pattern may be established early but some patients become compliant only after several weeks of adaptation

CPAP improves but does not abolish all symptoms of sleepiness - blood pressure frequently decreases with CPAP Surgical treatments of sleep apnea tend to be better for snoring than for the obstructions

Laser uvulectomy (LAUP) is not an operation for sleep disordered breathing - there is no evidence of effectiveness

Pharyngeal surgery (UPPP) is occasionally effective but true "cures" occur in fewer than 30% of cases; difficult to predict who will respond; may make later CPAP therapy less effective; improvement tends to wain with time

Maxillofacial surgery is of unproven effectiveness; staged procedures; only one center reports high success rates; few patients are willing to undergo facial reconstruction Mandibular positioning devices (dental appliances) now are an alternative to CPAP for some patients

Successful in approximately 60% of patients

Long-term side effects remain unclear (TMJ problems; occlusion difficulties)

Prevent obstructions more effectively than desaturations

Process of construction and advancement to a therapeutic position may take months and reimbursement may be a problem

6. Effective pharmacological therapies exist for narcolepsy and for periodic movements in sleep syndrome

Stimulant medication will ameliorate the symptoms of sleepiness experienced by narcoleptic patients

Although current stimulants have unpleasant side effects and are limited in their duration of action, newer agents will likely provide greater relief

Modafinil is a new longer-acting agent that acts through different pathways (as yet undefined) to improve alertness