Pearls: Sleep Disorders

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1 Pearls: Sleep Disorders Suzanne Lesage, M.D. 1 ABSTRACT Sleep disorders and sleep complaints are common in the neurology patient. A good history can often be started with just a few well-worded questions to help identify the major sleep disorders. Identifying sleep-related disorders can help the neurologist broaden the differential diagnosis and treat disorders that can contribute significantly to many comorbidities of other neurologic diseases. KEYWORDS: Sleep disorders, restless leg syndrome, periodic limb movement disorder, parasomnia The importance of a good night s sleep cannot be underestimated. Poor or inadequate sleep has been associated with mood disorders, cognitive difficulties, increased sensitivity to pain, and cardiovascular disease. In addition, there has been a growing awareness of the impact of sleep disorders in neurologic diseases, including an increased prevalence of restless leg syndrome (RLS) in multiple sclerosis, a contribution of obstructive sleep apnea to cerebrovascular disease, and a high prevalence of rapid eye movement (REM) sleep behavior disorder (RBD) in a-synucleinopathies (e.g., multiple system atrophy and Lewy body dementia). 1 3 Too often, sleep disorders are overlooked in a neurologic history, yet a basic knowledge of sleep and sleep disorders along with a systematic approach to their evaluation can result in better management of the neurology patient. The key to evaluating sleep disorders is clinical history. Although disorders such as narcolepsy, parasomnias, and RLS can produce profound subjective complaints, they generally have little or no findings on physical examination. Despite the lack of physical signs, many key symptoms, such as cataplexy, are unique, and with a few well-worded questions a correct diagnosis is easily at hand. Like many diagnostic procedures, sleep studies, including overnight polysomnography (PSG) and the multiple sleep latency test (MSLT), are used to confirm a suspected diagnosis based on the history. A common reason for misdiagnosis or a patient s failure to respond to treatment is the result of depending solely on findings from a sleep study, while failing to recall a patient s complaint or not taking an adequate sleep history. GETTING A SLEEP HISTORY In a general sense, sleep disorder patients present with two main complaints: difficulty sleeping at night and daytime sleepiness. Often, the patient suffers from some combination of the two. In addition, individuals will seek medical attention solely on the recommendation of a bed partner whose own sleep is in jeopardy because of unwanted snoring or excessive movements at night. Therefore, the first key is to obtain a history both from the patient as well as a bed partner, if available. General sleep habits Ask about bedtime, including average time it takes to fall asleep (sleep latency), number of awakenings at night, rise time, and average hours of sleep per night. Remember that individuals frequently have different patterns of sleep on the weekend and during vacations when not attempting to conform to work hours. Asking about weekend sleep, or simply asking 90 1 Sleep Disorders Center, Walter Reed Army Medical Center, Washington, District of Columbia. Address for correspondence and reprint requests: Suzanne Lesage, M.D., Sleep Disorders Center, Walter Reed Army Medical Center, 6900 Georgia Avenue, Bldg. 2, 7623, Washington, DC ( Suzanne.lesage@us.army.mil). Neurologic Pearls; Guest Editor, Stephen G. Reich, M.D. Semin Neurol 2010;30: Copyright # 2010 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) DOI: ISSN

2 PEARLS: SLEEP DISORDERS/LESAGE 91 the patient to imagine their sleep schedule if they had no social and work obligations, can reveal naturally early or late risers and short and long sleepers. Sleep habits/sleep environment A few key questions can help get to the core of an individual s poor sleep, including what he or she drinks with an evening meal (caffeine or excess alcohol) and a description of typical bedtime routine. These questions can reveal habits like leaving the television on the entire night while attempting to sleep or working on the computer in bed or right before sleep. Evaluation of daytime sleepiness Napping during the day: Napping can be a sign of daytime sleepiness if an individual has adequate sleep at night; often napping in the afternoon is a natural part of the circadian cycle for individuals with short sleep times overnight. Sleepiness in sedentary activities: Ask patients how often they fall asleep watching television, if they can watch an entire movie, or if they tend to fall asleep during religious services. Sleepiness during activities: Ask about drowsiness during driving, accidents or near accidents due to sleepiness, and sleepiness in daytime activities (for example, sleeping during meetings or on the phone). These evaluations can also be accomplished by having the patients complete an Epworth Sleepiness Scale, an easy and quick survey of eight questions, with each question graded on a scale of0to3onthechanceofdozingindifferent situations. Scores 11 indicate sleepiness and 16 indicate severe sleepiness. 4 Associated sleep complaints Snoring is very common. Instead of asking about the presence of snoring, ask how loud nightly snoring is (enough to be heard in another room?). Loud habitual snoring has been shown to be a better predictor of sleep apnea then snoring alone. 5 When asking about movements at night, ask about brief repetitive movements, such as periodic limb movements (PLMs), and complex movements including sleepwalking, sleep talking, and flailing movements. A bed partner s input is very useful. Specific disorders are discussed in the following sections. SLEEP DISORDERED BREATHING A brief note for the neurologist: One should have a low threshold for ordering a sleep study to evaluate for sleep disordered breathing. If an individual is obese (body mass index [BMI] 30), snores, and is hypertensive, or if he or she complains of daytime sleepiness, do not hesitate to get a sleep study. Because of the increased prevalence of sleep apnea in many neurologic disorders, there is a high positive predictive value of having significant sleep apnea on a PSG in individuals with these characteristics. Successful treatment can prevent many comorbities, such as headaches, mood disorders, cognitive difficulties, and hypertension. RESTLESS LEG SYNDROME AND PERIODIC LIMB MOVEMENT DISORDER Restless leg syndrome and periodic limb movement disorder (PLMD) represent two disorders. Restless leg syndrome is based on clinical criteria, not on PLMs from a sleep study. Periodic limb movement disorder, on the other hand, is a combination of clinical symptoms a complaint of difficulty sleeping or daytime sleepiness in addition to the presence of >15/hour of PLMs on a PSG in an individual who does not have RLS. 6 Examination One of the interesting features of idiopathic RLS is profound subjective complaints with no abnormalities seen on a general neurologic examination. Despite this, there are numerous reports of secondary RLS associated with polyneuropathy, radiculopathy, and peripheral nerve lesions. Therefore, it is important to do a neurologic examination directed toward these conditions. Findings suggestive of neuropathic processes can help focus a history as well as select a specific treatment. For PLMD, underlying neurologic conditions may even play a greater role in producing PLMs. In addition to previously mentioned disorders, PLMD and, to a lesser extent, RLS are frequently seen in myelopathic processes. Medication History Medications can play a role in aggravating or causing RLS, and this is seen to a much greater degree in PLMD. Remember to ask about over-the-counter medications because many patients use them to help them sleep, with diphenhydramine being the most common ingredient. Just like the known paradoxical reaction of agitation that can occur when some individuals take H1 histamine receptor antagonists, RLS patients also comment that these agents can induce or aggravate RLS symptoms.

3 92 SEMINARS IN NEUROLOGY/VOLUME 30, NUMBER Selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors have been reported to cause or increase RLS and PLMs. A short list includes fluoxetine, mirtazapine, paroxetine, sertraline, and venlafaxine. 7 Dopamine agents help alleviate RLS and reduce PLM, so it follows that agents that are dopamine blockers, like antipsychotics and antiemetics, can increase RLS. Both the phenothiazine derivatives and the novel antipsychotics are associated with PLMs. It is important to get a history that a medication corresponds to symptom onset or progression in patients taking dopamine blockers. Many RLS patients suffer from anxiety and/or depression and benefit from treatment for these conditions. 8 Antidepressants are not an absolute contraindication few reports link tricyclic antidepressants to inducing RLS, and buproprion has shown no increase in PLM or RLS. 7 RESTLESS LEG SYNDROME Idiopathic RLS, when not complicated by other factors, is fairly unique in its constellation of symptoms. Patients complain of a very uncomfortable, annoying sensation associated with a need to move one s legs: I just can t keep them still. This occurs when the patient is resting at night before bed, either sitting or supine, and the ache is relieved when walking. However, for the neurologist seeing patients with concomitant neurologic problems, these complaints present a diagnostic challenge. Many pain-related conditions make it more difficult to distinguish RLS from potential mimics and to accurately assess and treat those with overlapping symptoms, such as occurs with RLS and polyneuropathy. Common mimics of RLS include neuropathy (it is not uncommon for pain in many conditions to increase at night), radiculopathy, nocturnal muscle cramps, positional discomfort, and volitional rocking movements of the legs. 9 To help differentiate RLS from other possible diagnoses: The sensations in RLS are numerous and varied, but in general when given a choice between pain and discomfort, patients with idiopathic RLS choose discomfort compared with individuals with other painrelated syndromes (muscle cramps, radiculopathy). However, one has to phrase the question properly by providing a choice of terms: Are the sensations painful or rather uncomfortable? Otherwise, pain is a catchall phrase that patients will rely on to describe all types of sensations. In those that do describe pain, sensations are deep, creepy crawly, and aching, unlike the classic burning or numbness reported for neuropathic pain. The sensations also tend to be in the legs rather than just the feet. Despite these differences, pain remains a symptom for some RLS patients. 10 Because of difficulty with the unclear sensory symptoms, the urge to move while at rest is a more useful symptom. When questioning patients, try to ask how difficult it is to remain still. Individuals with RLS will say that confining situations, like sitting in a cramped space in the evening, are difficult to tolerate. Individuals with neuropathy at night may prop the feet up or remove them from under the covers, but do not often feel an irresistible desire to get up and walk or move, and the movement generally does not relieve the discomfort. RLS sensations never start when a patient is walking, unlike neuropathy or radicular discomfort. For patients who have a known neuropathy, it is useful to see if they can separate the two types of discomfort. The more typical neuropathic symptoms, such as burning or numbness, may be felt during the day; these symptoms are separate from those that give patients the urge to move at night and that are relieved with walking. For complicated patients with multiple pain syndromes, a trial of a dopaminergic medication either a dopamine agonist (pramipexole, ropinirole) or levodopa/carbidopa at night is worthwhile. With a nearly 70 to 80% response rate, a dopaminergic medication can help distinguish RLS from other pain syndromes. 11,12 Other mimics of RLS: Individuals who have volitional rocking or tapping of the legs can be unaware of the movement until someone else comments, and it is not associated with discomfort or an irresistible urge to move. Nocturnal leg cramps are an almost universal experience. Patients describe a cramping or muscular contraction that is relieved with stretching or rubbing. They generally occur out of sleep rather than before sleep onset. They are often more painful than RLS and are associated with a visible muscle contraction. Charlie horse cramp is a familiar term, and when most idiopathic RLS patients are asked, they can easily distinguish between nocturnal leg cramps and RLS. Discomfort from arthritis and radicular pain is relieved with simple positional changes, whereas relief from RLS tends to involve more complex movements, such as walking, kicking, rocking, or stretching. 9 RLS caveats: Some patients have very little sensory symptoms, but instead have involuntary limb movements while rest-

4 PEARLS: SLEEP DISORDERS/LESAGE 93 ing. They describe a buildup and then a brief jerk of the legs at rest. These are PLMs while the patient is awake. Periodic limb movement while awake is a good marker for RLS; however, many sleep studies do not report PLM during wakefulness. 13 Sleep deprivation exacerbates RLS. Ask about basic sleep hygiene, and make sure individuals are getting enough sleep. Iron deficiency is associated with RLS. 14 Because frequent blood donations can be a potential source of iron deficiency, ask patients about their blood donation history. PERIODIC LIMB MOVEMENT DISORDER Periodic limb movement in sleep is a nonspecific finding. Do not overreact to PLM observed during a sleep study. The following may help select individuals that would benefit from treatment: First exclude medications described previously as a cause of PLM. PLM increases with age; >50% of asymptomatic individuals older than the age of 65 years have PLM on sleep studies. 15 Individuals with neuropathy, Parkinson s disease, lumbar stenosis, and cervical stenosis or myelopathy may have PLMs on a sleep study. Unlike RLS, PLMs have conflicting results in regard to daytime consequences, such as excessive daytime sleepiness or decrease in quality of life. Therefore, treatment should be directed toward individuals in whom PLMs are felt to be the primary reason for poor sleep. 16,17 PLM is known to be part of an arousal response to sleep disordered breathing events. American Academy of Sleep Medicine (AASM) guidelines for scoring limb movements as PLMs exclude limb movements associated with a sleep-disordered breathing event, such as obstructive apneas. However, individuals may have more subtle patterns of inspiratory flow limitation associated with a limb movement that do not meet criteria for an apnea, and, depending on the scoring criteria used by a laboratory, these patterns may still be counted as PLMs. There is established evidence for sleep apnea causing sleep disturbance and daytime sleepiness, so it is better to treat the sleep apnea in patients with both apnea and PLM, and then reassess symptoms after successful treatment of sleep apnea. 18 PLM can be seen when patients are first titrated on continuous positive airway pressure (CPAP). In patients with an elevated number of PLMs associated with arousals or sleep fragmentation on a sleep study, it is helpful to take a thorough history for subtle RLS (e.g., only happens on long car rides or in airplanes) or a family history of RLS. Some individuals with PLMD may, in fact, go on to develop RLS. Individuals with a family history of RLS may represent a spectrum of RLS with the onset of the motor symptoms (PLM) as a prodromal symptom or as the only manifestation of the disorder. 19 NARCOLEPSY WITH CATAPLEXY Narcolepsy has no defining physical examination findings; instead, a good history is essential for diagnosis. An evaluation for narcolepsy is most often undertaken in young adults who present with significant excessive daytime sleepiness who are otherwise meeting their sleep needs (i.e., 7 or more hours of sleep per night), or in adults of normal weight without snoring with excessive daytime sleepiness. The neurologist also has to be aware of other neurologic conditions that have been noted to produce secondary narcolepsy (including some with low hypocretin-1 levels), such as in individuals with multiple sclerosis, tumors with hypothalamic involvement, myotonic dystrophy, traumatic brain injury, paraneoplastic syndrome (anti-ma2), and Niemann-Pick disease, to list a few. Although excessive daytime sleepiness can prompt an evaluation for narcolepsy, cataplexy is pathognomonic for the disease and can be used, along with excessive sleepiness, to make a diagnosis. Cataplexy is episodic, triggered weakness with bilateral loss of muscle tone. It is common to ask about falling or weakness in the knees after laughter; however, weakness frequently is more subtle and can affect only the head and neck. It is just as useful to ask about one s head falling forward, jaw dropping, slurred speech, or ptosis. Cataplexy triggers are positive emotions, with laughter being the most common trigger. Many patients also relate triggers to be excitement, startle response, or anticipatory anxiety. Some examples of triggers from patients include the excitement when a fish bites a fishing line, the moment before striking a tennis ball, or right before hitting a nail with a hammer. Greater emotions or withdrawal from anticataplexy medication can produce profound cataplexy that involves many muscle groups, lasts longer, or leads to a flurry of brief attacks. The episodic nature of the weakness can lead to misdiagnosis as seizures or transient ischemic attacks (TIAs). Distinguishing features of cataplexy include the brevity of the events (seconds instead of minutes), no loss of consciousness or awareness, and the fact that cataplexy involves bilateral weakness. Individuals with other causes of excessive daytime sleepiness will complain of weakness when sleepy or

5 94 SEMINARS IN NEUROLOGY/VOLUME 30, NUMBER brief sleep attacks where they doze briefly and lose muscle tone. Sleepiness can exacerbate cataplexy, but the preceding emotional triggers and clear awareness during the event can distinguish cataplexy from sleep attacks. Unlike cataplexy, other REM intrusion-related symptoms, including sleep paralysis and hypnagogic hallucinations, can occur as an isolated symptom or part of other medical conditions. Sleep paralysis is common and is exacerbated by sleep deprivation. Sleep paralysis is sometimes confused with sleep drunkenness or sleep inertia. Sleep inertia occurs as individuals attempt to wake up before meeting their sleep needs. However, unlike sleep paralysis, where individuals are awake or even anxious, sleep inertia individuals are sleepy and have difficulty gaining full alertness. Patients with definite cataplexy and excessive daytime sleepiness meet criteria for the diagnosis of narcolepsy; however, PSG and an MSLT, which consists of five 20-minute naps during the day is recommended to both evaluate for other disorders, such as sleep apnea, and help confirm the diagnosis. NARCOLEPSY WITHOUT CATAPLEXY A diagnosis of narcolepsy without cataplexy is made on the basis of an MSLT result of at least two REM onsets and a mean sleep latency of less than 8 minutes. Individuals without cataplexy are a more heterogeneous group of patients. Unlike the >90% of narcolepsy with cataplexy that have low cerebrospinal fluid (CSF) hypocretin-1 levels, low hypocretin-1 levels are seen in only 10 to 20% of individuals without cataplexy. 20 The diagnostic dilemma for diagnosing narcolepsy without cataplexy is relying on results from a test that has notable limitations. Misleading results with the MSLT primarily arise when not done under set recommendations and standards. Sleep apnea, sleep deprivation, delayed sleep phase syndrome, shift work, and REM suppressant medication rebound are just some of the conditions that can give false-positive results. 21 It is worthwhile to review the sleep study for the following before making a diagnosis that is lifelong. The MSLT should be preceded by an overnight PSG. A prior night s sleep study is beneficial for the following reasons: to observe and document other sleep disorders (sleep apnea, PLM); to look for early nocturnal REM onset; to assure an adequate sleep time for the next day s MSLT, allowing the individual to sleep at least 7 to 8 hours to assure that sleep loss does not alter results. Patients should have adequate sleep at least 1 week before the study. Although sleep times vary, if a person is being evaluated for daytime sleepiness, adequate sleep means individuals should, on average, get 7 to 9 hours per night. Of note, narcolepsy can be associated with fragmented sleep, although this tends to happen later. Most patients report falling asleep easily but with multiple awakenings over the night. Therefore, it is helpful to at least document that individuals are allowing the time to get enough sleep at night or over a 24-hour period, including naps. Sleep logs, or for more accuracy actigraphy, can be used to document sleep times. Individuals also need to be sleeping regularly at night for a daytime MSLT. Shift workers and other circadian rhythm abnormalities can result in REM onsets during nap testing. Stimulants and stimulant-like medications, along with REM suppressant agents, need to be discontinued for 2 weeks before the test. In practice, the most difficult agents are REM suppressant agents because this includes the majority of antidepressants. These agents can either suppress REM or are associated with REM rebound on naps during withdrawal. Thus, the 2-week period allows an individual to withdraw the medication as well as recover from REM rebound. 21 PARASOMNIAS Parasomnias, broadly categorized, are nonvolitional complex behaviors that occur during sleep or during arousals from sleep. Typically, the parasomnias are subdivided into non-rem (NREM)- and REM-related events; however, several behaviors can arise out of any stage of sleep. Non-REM-related events include sleepwalking, sleep terrors, and confusional arousals. The REM-related parasomnias include RBD and nightmare disorders, with other common behaviors including sleeprelated groaning and rhythmic movement disorder. For the neurologist, parasomnias are an important part of their diagnostic repertoire, as they need to be able to distinguish parasomnias from nocturnal seizures and identify RBD as a key symptom in a-synucleinopathies. Examination Because of the high prevalence (30 to 60%) of a-synucleinopathies with RBD, a neurologic examination, including cognitive screen for dementia, signs of parkinsonism, cerebellar signs, autonomic dysfunction, and olfactory dysfunction, is an important tool. 22 Because RBD has been shown to manifest before any other neurologic symptoms, ongoing periodic evaluations should be done, but one should do so acknowledging that a significant percentage of chronic RBD remains idiopathic so as not to unnecessarily alarm patients. Medication history Medications can induce all types of behaviors that can appear to be both REM and NREM

6 PEARLS: SLEEP DISORDERS/LESAGE 95 parasomnias. Selective serotonin reuptake inhibitors, antipsychotics, and atypical benzodiazepines (zolpidem) can produce sleepwalking, sleep talking, and nighttime eating disorders. It can be difficult to distinguish between a medication-induced behavior and a true parasomnia. Social history Ask about alcohol use, sleep deprivation, change in environment, and social stressors that can produce or aggravate many parasomnias, primarily the NREM parasomnias. Sleep disorders Don t forget to ask other sleep-related questions, especially about snoring and witnessed apneas. Arousals from sleep apneas can produce some behaviors that can sound like parasomnias and can aggravate underlying parasomnias. NON-RAPID EYE MOVEMENT PARASOMNIAS Below are some features that can differentiate between NREM and REM parasomnias. Non-REM parasomnias, like sleepwalking and sleep terrors, occur in the first third of the night (first 2 hours after sleep onset). This is the part of the sleep period that produces the greatest portion of slow-wave sleep. Individuals tend to be amnesic for the event when awakened. Another helpful characteristic of NREM parasomnia is onset in childhood. Adults that present with NREM parasomnias should be asked about childhood sleep behaviors because most adults (80%) report childhood symptoms. 23 Ask about a family history. Several studies have demonstrated an increased prevalence in family members. The same association is not seen in REM-related disorders. 24 To help differentiate NREM parasomnias from nocturnal seizures, it is helpful to remember that behaviors like sleepwalking, sleep terrors, and sleep talking are common. They have a much higher prevalence than nocturnal seizures and have fairly classic behaviors. However, many of the confusional arousals can be brief with less complex movements and can be similar to behaviors seen with frontal or temporal complex seizures. A single-night routine PSG is not useful for NREM parasomnias. The events are sporadic, and most individuals lack any other finding on the PSG unless additional symptoms (snoring) suggest sleep-disordered breathing. For individuals with behaviors at night that are atypical and suggestive of possible seizure, prolonged monitoring is needed. This can be accomplished with either a PSG that is set up with a full seizure montage and continuous video recording or prolonged epilepsy monitoring. Because the events are sporadic, epilepsy monitoring units that allow monitoring for more than one night are useful. RAPID EYE MOVEMENT PARASOMNIAS Age of onset is older than for NREM parasomnias, typically seen more in men after the age of 50 years. In individuals younger than 50 years, one should look for disorders associated with RBD, such as narcolepsy or medication-induced behaviors. 25 The first REM period is 90 minutes after sleep onset, so REM behaviors occur later in the sleep period. REM periods get longer as sleep progresses, so many REM parasomnias happen in the early morning hours. Individuals typically recall a dream when awakened. The behaviors in REM behavior disorder are more likely to be aggressive with flailing, punching, and screaming or yelling. It is not atypical for the dreams of RBD to be violent in nature and involve aggressive behaviors or running away. Because of the violent quality, patients may be reluctant to talk about the dreams. It is helpful to alleviate these patients anxiety by explaining that RBD dreams can be violent without denoting any underlying psychological meaning. Unlike NREM parasomnias, PSG is useful and necessary for the diagnosis of RBD. A sleep study can demonstrate increased muscle tone and increased phasic movements during REM even in the absence of any events. It is also common to see excessive PLMs as a part of RBD. 26 Medications (SSRIs are the best documented) have been shown to increase REM electromyographic (EMG) tone. This fact needs to be kept in mind when interpreting both the behaviors and the PSG findings. 27 Nightmare disorder is a type of REM parasomnia. It is common in post-traumatic stress disorder (PTSD). Difficulty arises in distinguishing between nightmare disorders and RBD. Because some treatments (antipsychotics, antidepressants) that help PTSD nightmares may worsen RBD, it is helpful to try and distinguish the two. The dreams in nightmare disorder tend to be recurrent and related to traumatic events, unlike RBD where dreams can be more random and include events that the patient never previously experienced.

7 96 SEMINARS IN NEUROLOGY/VOLUME 30, NUMBER Dreams in both disorders can be anxiety provoking and associated with fear; however, fear, anxiety, and emotional recall related to the dreams are often greater in nightmare disorder. Although individuals can have some movements (punching/kicking) associated with the nightmares, it is not as common as that seen in RBD. Sleep terrors, although most commonly seen in childhood, can also be seen in adults and can produce violent behaviors, such as screaming and running, but like the childhood syndrome, the individual is amnestic about the event. Sleep disorders are common in neurologic patients. Asking a few key questions about sleep, snoring, and movements can open the door to evaluating and treating sleeping problems that can ultimately benefit the patient, not only by treating the sleep disorder, but also by possibly improving the patient s other neurologic symptoms. REFERENCES 1. 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