Family Practice Issues in Neurology

Fall 1999
Volume 10, Number 2

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Excessive daytime sleepiness, or hypersomnia, accounts for a substantial percentage of patients with sleep complaints. Basic medical evaluation, coupled with analysis of a patient’s sleep pattern and supplemented by sleep laboratory testing, usually is helpful in arriving at a specific diagnosis, and treatment plan. Sleep timing and circadian disorders; obstructive sleep apnea; narcolepsy; and periodic limb movement disorder are the more common causes of excessive daytime sleepiness.

Introduction. Many people have sleep complaints. On any given night, 25% to 30% of the North American population may complain of sleep problems. Insomnia is still the primary complaint. It may be difficult to decide if a patient is, indeed, suffering from sleepiness since patients who are suffering from sleepiness tend to focus on their sleep patterns at night only. Many patients feel they must have insomnia if they are so tired during the day. This is not always the case.

Another important consideration is the patient with a chronic fatigue syndrome. Trying to decide if a patient is fatigued or excessively sleepy can be very difficult. The Multiple Sleep Latency Test (MSLT), is one measure to objectively see if a patient is suffering from excessive sleepiness.

It is important to emphasize certain points in a patient’s sleep pattern on history. The time a patient gets into bed, and the time a patient falls asleep are 2 different time points that need to be specifically defined. When a patient wakes up and when a patient gets out of bed may be different. Arousals at night, cause for them, and their duration need to be systematically asked. Weekend adjustments in sleep patterns, and napping during the day usually complete a sleep pattern history.

To objectify this aspect of a patient’s history, one may want to use a sleep log. Sleep measurements can be obtained to see if a patient is sleepy. One easy to administer sleep questionnaire is the Epworth Sleepiness Scale.1 It is a simple 8-item questionnaire. Scoring is done on a 0 to 24 point scale. Normal is debated, but in general is considered between 5 and 8. It is interesting to note that patients with insomnia usually have scores of 4 and under, perhaps consistent with an element of hyper arousal. Patients with an Epworth Sleepiness Score over 10 usually are, indeed, suffering from significant daytime somnolence. Scores over 20 may point to severe sleepiness or other factors for which the patient wants to impress upon the physician that they are, indeed, sleepy.

Environmental influences on sleep include alcohol use, tobacco use, and the sleep environment. Over-the-counter medications are sometimes paradoxically misused by patients with excessive sleepiness. They may assume that they “have insomnia” and medicate themselves with antihistamines or melatonin in an attempt to improve nocturnal sleep when this may not be the issue at hand. Besides over-the-counter medications, prescription medications can also influence daytime alertness. Medical illnesses and prescription medication use related to the timing of onset of excessive sleepiness is seen if these are contributing factors to hypersomnolence.

Disorders of Sleep Timing. Sleep timing and circadian disorders can be obvious in some patients suffering from excessive sleepiness; for example, patients with jet lag or shift-work syndrome. Irregular sleep pattern syndrome or the syndrome of chaotic sleep patterns in a patient with excessive sleepiness is usually secondary to an underlying psychiatric disorder or intrinsic circadian disorder resulting in disrupted sleep. However, more common disorders of sleep timing may be very insidious in their clinical presentation.2

Insufficient Sleep Syndrome. Insufficient sleep syndrome, as its name implies, is a disorder in which chronic sleep deprivation has occurred in a patient. Duration is usually more than 3 months. Diagnosis is usually made when the patient relates a history of improvement in his or her symptoms while on vacation or during weekends. During these times when sleep recovery is allowed, the patient may have increased duration of sleep episodes for one to 7 days, followed by a resolution of symptoms. College students and “2-job” workers are very prone to this disorder. Other at-risk groups include people with a biological need for 9 or more hours of sleep per day, or those suffering from delayed sleep phase syndrome.

Delayed Sleep Phase Syndrome. Delayed Sleep Phase Syndrome (DSPS) is seen when the intrinsic sleep time of a person is delayed with respect to the desired (clock) sleep time. This results in 2 problems. The patient may have sleep-onset insomnia, and they may also have difficulty in awakening. It is the difficulty in awakening that usually brings the patient to the physician. It is this complaint that can be misinterpreted as excessive daytime somnolence.

In the clinical setting DSPS is primarily seen in high school students. This is because sleep patterns are naturally delayed in adolescents and tend to advance as we get older. In this author’s experience, it appears that girls make their way to sleep disorder clinics more frequently than boys, although published gender distributions favor this disorder occurring more frequently in boys. The key to diagnosis of this disorder is, again, the patient’s behavior while on vacation or when “off cycle” from school. These patients tend to go to bed between 2:00am and 4:00 am, wake up between 10:00 am and 2:00 pm, and feel alert and refreshed until their next, relatively delayed to society, sleep time.

Treatment of DSPS can be very difficult because, in essence, treatment is fighting against a patient’s natural biological rhythms. However, sleep hygiene practices, coupled with melatonin at night, are very important. Transient nocturnal sedative-hypnotic use with melatonin is debated but may be indicated in certain patients. Early-morning exercise and bright light also help phase-advance a patient’s sleep timing. Naps should rarely be prescribed or allowed. However, if they are, they should be completed by 2:00 pm at the latest. Naps later in the day tend to phase-delay these patients.

Advanced sleep-phase syndrome. Advanced sleep-phase syndrome (ASPS) is much rarer than delayed sleep phase syndrome. Here, patients tend to fall asleep or develop excessive sleepiness prior to the time until which they would like to stay awake. This may be coupled with the complaint of an early final awakening. As can be seen, this is the inverse situation from DSPS. Diagnosis is usually made in those patients who, when allowed to sleep without any extrinsic constraints, fall asleep between 7:00 pm and 9:00 pm, usually sleep until 2:00 am to 4:00 am, awaken and feel fine and refreshed the entire day. Usually this situation, although rare, can be seen in the elderly. Treatment usually is simple patient education and physician support in maintaining a good sleep hygiene program around these patients’ normal biological rhythms.

Sleep can be delayed by bright light exposure and exercise late at night, after 7:00 pm. Early morning or early day use of melatonin also tends to phase-delay a person’s sleep rhythms. As stated above, late-day naps after 3:00 pm also tend to phase-delay anyone, including those patients suffering from ASPS.

Narcolepsy. An interesting disorder of excessive sleepiness is narcolepsy. It is not that uncommon, occurring in one in every 2000 to 3000 people. It has an equal distribution between men and women, and it is a lifelong disorder with symptom onset usually in early adolescence. It may not be diagnosed until very late in life. It is characterized by recurrent episodes of sleep attacks in association with daytime sleepiness. The clinical diagnosis is made if the sleepiness and sleep attacks occur in association with the symptom of cataplexy.

Cataplexy. Cataplexy is episodic loss of motor control usually precipitated by strong emotional stimuli, such as acute fear or laughter.3 Classical teaching would have clinicians believe that narcolepsy manifests itself as complete loss of motor control with falling. However, the usual clinical presentation is more subtle.3 More focal or regional head dropping, arm dropping, or knee buckling is usually the manifestation of cataplexy.

Hypnagogic hallucinations. Hypnagogic hallucinations are dream imagery seen by the patient usually at sleep onset, but may also be seen at awakening. This probably is a manifestation of abnormal REM sleep during transition into deeper stages of sleep.

Sleep paralysis. Sleep paralysis is the inability to move upon awakening. The patient eventually does begin to move, perhaps in response to sensory stimuli. The hallmark of the diagnosis of sleep paralysis is the terrifying quality that the patient communicates when he or she experiences this symptom.

Automatic Behaviors. Automatic behaviors may occur in any patient with a disorder of excessive sleepiness, but are commonly seen in narcoleptics. Patients with automatic behaviors may do things such as forget to turn off stoves, drive long distances while missing exits, or place things in inappropriate parts of the house. Narcoleptics also may have vivid dreaming upon napping.

Most clinicians are not aware that narcoleptics usually have disturbed nocturnal sleep, and indeed, may also have the complaint of insomnia. When one looks at the total amount of sleep time per day of the narcoleptic, it is very close to that of non-narcoleptic subjects, pointing to the fact that narcolepsy may be considered more of a sleep-timing disorder.3

The differential diagnosis of narcolepsy is very extensive. However, other sleep disorders need to be considered. Obstructive sleep apnea can present with excessive sleepiness. This disorder is described below. It is important to realize that in those with narcolepsy, obstructive sleep apnea is very common, and failure to recognize this comorbidity may thwart therapeutic intervention.

Idiopathic Hypersomnia. Idiopathic hypersomnia is a neurological disorder associated with increased sleep and sleepiness. However, there are none of the associated REM-related symptoms, such as cataplexy, sleep paralysis, or hypnagogic hallucinations. On multiple sleep latency tests, these patients do not demonstrate abnormalities of REM sleep.

Medical and psychiatric differential diagnoses include chronic fatigue syndrome, depression, and hypothyroidism. Neurological disorders can present with narcolepsy. Diseases that cause subcortical or brain stem lesions include tumors, multiple sclerosis, and trauma, which can create symptomatic narcolepsy as opposed to idiopathic narcolepsy. Atonic seizures usually are easily differentiated from cataplexy on clinical grounds. Occasionally, neuromuscular disorders or chronic myopathies can be misinterpreted as fatigue and cataplexy, although this difference is usually clinically apparent.

The workup of the patient with narcolepsy includes a basic medical evaluation. Basic laboratory studies should include a complete blood count and thyroid functions. However, it is sleep testing that helps confirm the diagnosis. Nocturnal polysomnography can be helpful, especially in eliminating other causes of excessive sleepiness. However, the key test for diagnosis is the multiple sleep latency test (MSLT). In this test, a patient naps 4 or 5 times intermittently throughout the day. The time to fall asleep, and the stage of sleep are measured in each nap. Normals usually average over 10 minutes in falling asleep, and usually never go into REM sleep. Classically, narcoleptics will average sleep onset under 5 minutes and have 2 sleep onset REM periods.4

Narcolepsy has a very high association with certain HLA markers.3,5 The original DR-2 subtype was not as strongly associated in Caucasians and African-Americans. However, recent subtypes have shown a very high association across these ethnic groups.

It is important to realize that although the association with the HLA subtypes is very high, these subtypes are found in up to one-third of the population. Therefore, there is a high “false positive” rate of HLA findings in patients. An HLA test occasionally can assist a physician in eliminating a diagnosis of narcolepsy.

Treatment of the disorder usually requires 3 approaches. The first is attention to the patient’s sleep hygiene. This includes timed naps and timed caffeine intake. The associated symptoms of cataplexy, sleep paralysis, and hypnagogic hallucinations are treated primarily with tricyclic antidepressants. Clomipramine (Anafranil) and protriptyline (Vivactil) are primary agents recommended by this author. Supplemental agents include beta-blockers or selective serotonin-reuptake inhibitors.

Treatment of excessive sleepiness has historically been centered around the stimulants. This includes methylphenidate, pemoline, and amphetamine. These drugs work by increasing dopamine release diffusely in cortical and subcortical structures. They are very effective in promoting alertness. However, their stimulatory effects “spill over” in creating hypertension, anxiety, and palpitations. Tolerance and addiction can also occur, and aggressive management of these agents is necessary.

More recently, a new agent has been approved for the treatment of narcolepsy - modafinil (Provigil). This is a wakefulness-promoting agent. It stimulates specific subcortical areas of the brain to promote wakefulness.6 There appear to be fewer stimulatory side effects, and fewer effects on cardiovascular functioning. There may also be fewer tolerance and addictive qualities to this new agent. There is great interest in this new agent in possible future applications in other disorders of excessive sleepiness.6

Obstructive Sleep Apnea. Obstructive sleep apnea is an extremely common disorder. It affects 1% to 3% of the adult population of the United States. It is seen commonly in those with increasing age, and is more prevalent in men than women.8

Obstructive sleep apnea is the disorder or periodic pauses in breathing during sleep due to abnormal obstruction of the upper airway. This is due primarily to abnormal motor control of oropharyngeal structures. These periodic pauses result in periodic awakenings, usually due to hypoxia. This results in sleep fragmentation and, subsequently, daytime hypersomnolence. The disorder of upper airway resistant syndrome (UARS) is the disorder of excessive snoring and sleep fragmentation without the overt obstructions in classic obstructive sleep apnea.7

The associated symptoms of obstructive sleep apnea include snoring, morning headaches, morning dry mouth, and observed apneas usually by the bed partner. There are increased movements and disrupted sleep. This is usually observed by the bed partner. The resultant sleep fragmentation causes mental status lapses with decreased memory and, perhaps, irritability. It is not uncommon for obstructive sleep apnea to present as a symptom of a motor vehicle accident.

These patients on examination are classically obese. Examination of the oropharynx can reveal increased tonsillar size or a decreased diameter in the anteroposterior plane. These patients may have associated cardiac arrhythmias, polycythemia, or hypertension. Hypertension may be due to the abnormal adrenergic release that occurs in response to the periodic hypoxia that occurs in sleep. Indeed, obstructive sleep apnea may be one of the few direct treatable causes of hypertension. If the disorder goes untreated for long periods of time, right heart failure can be an end-stage symptom.

Obstructive sleep apnea may exist as a comorbidity in other disorders of excessive sleepiness, and must always be considered or eliminated in those patients complaining of sleepiness. Patients at risk for this disorder, besides those described above, include patients with underlying primary pulmonary disorders, spinal cord injuries, underlying neuromuscular disorders, or patients with upper airway or craniofacial deformities. Hypothyroidism, amyloidosis, and acromegaly are rare causes of obstructive sleep apnea.

The evaluation of the patient with suspected sleep apnea begins with examination with attention to upper airway structures. Evaluation should include chest x-ray, complete blood count, thyroid function tests, electrocardiogram, and any advanced cardiopulmonary testing that may be clinically necessary. The hallmark of the evaluation, for both treatment and diagnosis, is the nocturnal polysomnogram. It is during the nocturnal sleep study performed in a sleep laboratory that the amount and quality of the apnea can be measured. Sleep laboratory testing may also reveal that the obstructive apnea occurs in only specific stages of sleep (usually REM sleep) or in specific sleep positions (usually becoming more severe when the patient is on his or her back).

Treatment of the disorder begins with attention to sleep hygiene. Sedative-hypnotic use, alcohol use, and tobacco use by the patient need special attention. Sleep position can occasionally be altered in certain cooperative patients. Weight loss should be encouraged as needed, but this mode of therapy usually meets with clinical frustration.

The primary therapies of obstructive sleep apnea are “mechanical” therapies. Interventions to alleviate or prevent the obstruction are employed. The major therapy includes continuous positive airway pressure (CPAP) or bi-level positive airway pressure (B-PAP™). The pressures for these treatments can be determined as part of the nocturnal sleep laboratory evaluation.

Other therapies include dental devices, which are highly effective in mild to moderate cases, and occasionally indicated in severe cases. These devices position upper airway structures to prevent the obstruction from occurring at night. Various upper airway surgeries may be indicated to open upper airway passages, as well as to eliminate snoring. Upper airway surgery is especially effective in the treatment of UARS. In severe cases of obstructive sleep apnea, classic upper airway surgery may not be directly helpful. However, upper airway surgeries may make CPAP-intolerant patients tolerant or responsive to the therapy.8

Periodic Limb Movement Disorder. Periodic limb movement disorder (PLMD) is characterized by repetitive episodes of stereotype limb movements that fragment sleep. These movements usually occur in the legs, and reproduce the triple flexion response of the foot (“Babinski response”). PLMD used to be referred to as sleep myoclonus or nocturnal myoclonus.

PLMD usually results in excessive sleepiness and hypersomnolence, but occasionally the patient may complain of insomnia. PLMD is to be differentiated from restless leg syndrome (RLS), which is a disorder of sleep initiation. The RLS patient, by definition, must have a complaint of intense uncomfortable feelings of the legs that disrupt sleep onset and may respond to movement of the legs. This need to move the legs disrupts sleep onset. The PLMD patient, by contrast, may be totally unaware of the problem, and it is the PLMD bed partner that may bring this issue to the attention of the physician. Approximately 80% of patients with RLS may also have periodic limb movements, but only 40% of PLMD patients may have restless legs.9

The diagnosis of PLMD is made on the sleep polysomnogram. These studies routinely measure the amount of leg movements per hour of sleep (referred to as the periodic limb movement index, or PLMI). The amount of leg movements associated with arousals per hour of sleep (the periodic limb movement arousal index, or PLMAI) is also routinely measured. If age-specific values in the PLMAI are exceeded, laboratory confirmation of the diagnosis is made. PLMD may be caused by underlying neuropathies or myelopathies; chronic disrupted sleep from other untreated sleep disorders; or iron, magnesium or B12 deficiencies. These disorders should be pursued when clinically indicated. Tremors, akathisia, muscle cramps, myoclonus, or spasticity may mimic PLMD. Periodic limb movements can be exacerbated by tricyclic antidepressants, carbamazepine, or drug withdrawal states.

Treatment of PLMD centers on treating any underlying disorder that may be the primary cause. The pharmacologic treatment falls on 3 classes of agents. These include the benzodiazepines (primarily clonazepam), the opioids (codeine and propoxyphene), or dopamine agonists. Dopamine agonists have emerged as the drugs of choice for this disorder. Tolerance may develop to any of these agents, requiring dose escalation. Ultimately, in more difficult cases, cycling of these agents due to tolerance may be necessary. Polypharmacy with different classes of agents may also be necessary.10

Parasomnias. Parasomnias are disorders of arousal or disorders that occur during sleep transitions. Collectively, they are very common. This group of sleep disorders includes nightmares, sleep terrors, sleep-related panic disorders, sleep talking, and sleep walking. They are mentioned here for completeness sake because these disorders are unlikely to be associated with hypersomnolence.2

Excessive sleepiness in a patient with a parasomnia may need more specific evaluation, and the symptom of excessive sleepiness should not automatically be labeled as a symptom of the parasomnia. Untreated sleep-related seizures are one parasomnia that, indeed, can present as daytime hypersomnolence.

Conclusion. Unlike insomnia, where primary therapy may occasionally be empiric and based on symptom management, excessive daytime sleepiness and hypersomnolence usually require a more specific treatment approach. Luckily, those patients with excessive daytime sleepiness can be evaluated so that a specific medical diagnosis can be objectively obtained. Appropriate history and sleep laboratory utilization are necessary in making specific diagnoses in patients with complaints of excessive sleepiness.

Patients with hypersomnolence need individualized attention to their sleep patterns and sleep environment. Medical management otherwise will never reach its full effect in promoting a patient’s daytime alertness and, ultimately, a patient’s quality of life.
 

Address comments and questions to:
Ronald E. Kramer, MD
CNI Sleep Disorders Center
701 E Hampden Avenue,
Suite 530
Englewood, CO 80113

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