Neurologic Aspects of Sleep Medicine

Sleep Stages

The staging of sleep is based on the recordings of the EEG, chin EMG, and EOG made during polysomnography (PSG). The PSG is scored by assigning a sleep stage to each 30-second epoch recorded. The characteristics of the various sleep stages are summarized in Fig. 51-1 .

Sleep Patterns Across the Human Lifespan

Sleep patterns change markedly throughout the human lifespan. The most pronounced changes occur during the first year of life. Newborns enter sleep through REM sleep (called “active sleep” in the newborn), and then sleep alternates between REM and NREM in 50- to 60-minute intervals rather than the 90-minute cycles of adults. During the first year of life, EEG patterns develop to allow distinction between different stages of NREM sleep.

Stage N3 sleep is most prominent in childhood and decreases by almost 40 percent in the second decade of life. It further declines with age and is almost absent by the age of 60, especially in men, perhaps due to a decline in the amplitude of EEG waves from reduced synaptic activity.

REM sleep occupies 50 percent of sleep in the first year of life. By 6 years of age, REM sleep time is reduced to 20 to 25 percent of sleep and is maintained at this percentage into old age. REM sleep markedly declines with organic brain dysfunction.

Arousals and episodes of awakening from sleep increase dramatically with age and may correlate with an underlying sleep disorder, medical condition, or neurologic disease. The percentage of stage N1 sleep also increases with age, signifying more transitions between wake and sleep.

Sleep requirements change with age. A newborn sleeps about 16 hours per day. This falls to about 11 hours in children 3 to 5 years of age. Adolescents between 9 and 10 years of age require approximately 10 hours of sleep. Adults average 7.5 to 8 hours of sleep; although this duration remains steady into healthy old age, the ability to consolidate sleep into a single continuous sleep period declines. Elderly individuals may revert to a biphasic sleep pattern with increased daytime napping.

Clinical Evaluation

Complaints related to sleep and wakefulness are pervasive in the general population. Approximately 30 percent of adults report one or more symptoms of insomnia including difficulty falling asleep, staying asleep, awakening too early, or nonrestorative sleep. It is estimated that 4 to 21 percent experience EDS at least 3 days per week. Only 6 percent of patients with sleep complaints see a physician specifically for a sleep problem, and many others resort to over-the-counter medications or self-remedies.

Sleep disorders are associated with significant morbidity and mortality. Insomnia, for example, is associated with impairment of all aspects of quality of life including physical functioning, bodily pain, social functioning, and mental health. Obstructive sleep apnea (OSA) increases the risk of cardiovascular and cerebrovascular disease as well as causing motor vehicle accidents.

Individuals with sleep disturbances present with any of four main complaints. The first is insomnia, which may be described as difficulty in falling asleep or staying asleep, having an insufficient amount of sleep, or poor quality of sleep. The second is EDS, which may manifest as feelings of lack of energy or tiredness associated with naps, falling asleep at inappropriate times, or difficulty with concentration or memory. The most common cause of EDS is insufficient time for sleep. The third complaint is of abnormal sleep behavior, usually described by a bed partner. The fourth is of an inability to sleep at the desired time. A single sleep disorder may be associated with multiple complaints.

It is important to understand the motivation of patients in seeking treatment. For example, insomnia may impact job performance and cause a concern for loss of employment. A complaint of snoring may present only after a person is forced to sleep in a separate room to prevent disturbing a bed partner. The International Classification of Sleep Disorders (ICSD) has helped unify the approach to sleep complaints by classifying over 60 sleep disorders.

Patients should fill out a sleep questionnaire and a 1- to 2-week sleep diary. The questionnaire should address the patients’ usual sleep hours, nocturnal awakenings, daytime napping, work hours, snoring, daytime functioning, sleep environment, movements in sleep (e.g., leg movements), abnormal behaviors in sleep (e.g., sleepwalking), lifestyle factors (e.g., caffeine intake), weight changes, past medical history, social history, medications, family history of sleep disorders, and other sleep symptoms (e.g., cataplexy or sleep paralysis). A sleep diary should record the time of getting in and out of bed, sleep onset time, awakenings, naps, exercise, sleep medication, and caffeine intake. There are several scales used to assess the degree of daytime sleepiness in a person, such as the Epworth Sleepiness Scale, that can help with diagnosis.

In addition to general medical and neurologic examinations, the physical examination should include the patients’ weight, height, body mass index (BMI), blood pressure, and neck circumference. The upper airway should be inspected for pharyngeal narrowing, tonsillar enlargement, uvula enlargement or edema, a large tongue, low-lying palate, and micrognathia, all of which are risk factors for sleep apnea.

Laboratory Testing

Standardized Definitions

Insomnia is one of the most prevalent health complaints, with 30 to 50 percent of the population reporting transient insomnia. When even more specific diagnostic criteria are utilized, the rates still range between 5 and 20 percent.

Criteria for insomnia differ somewhat between the three main classification systems: International Classification of Diseases, 11th edition (ICD); Diagnostic and Statistical Manual, Treatment Revision, 5th edition (DSM-V-TR); and International Classification of Sleep Disorders, 3rd edition (ICSD-3). The ICSD-3 classifies insomnia based on duration of symptoms whereas the DSM-V focuses on medical or psychologic comorbidities presenting with insomnia symptoms.

For many years, insomnia was thought of as a symptom of another underlying condition. Classification symptoms all distinguish between forms of “primary” (insomnia occurring without any comorbidities) and “secondary” insomnia (insomnia due to another disorder). Clinical practice has traditionally been to treat the “cause” first, with the belief that insomnia would remit after the underlying condition was addressed. A major shift in this line of thought has taken place in recent years, with a significant amount of research negating the view of primary and secondary insomnia. The relationship between sleep and psychiatric disorders appears to be bidirectional, and causative factors can be extremely difficult to separate from the insomnia itself. The symptom of “nonrestorative” sleep has also been called into question as it is typically related to another sleep disorder that impairs sleep quality.

Risk Factors and Common Comorbidities

Insomnia is most commonly seen in women, older adults, populations with lower socioeconomic status, those with divorce or marital separation, and in those with comorbid psychiatric or medical disorders. Insomnia is commonly observed in neurologic disorders, particularly Parkinson disease, Alzheimer disease, epilepsy, stroke, multiple sclerosis, and traumatic brain injury. Patients with medical conditions such as pain disorders and heart disease are all at increased risk of insomnia.

Consequences

Insomnia is a risk factor for the development of anxiety, depression, substance use, and suicidality. It is also associated with poor attention and concentration, increased work absenteeism, higher medical costs, increased rates of motor vehicle accidents, more falls in the elderly, and reduced overall quality of life.

Clinical Assessment and Diagnosis

The history should focus on symptoms, chronology, exacerbating and alleviating factors, social, medical, and psychiatric precipitants and comorbidities, as well as previous therapies and their success. Symptoms of insomnia range from difficulty in falling or staying asleep to early morning awakenings, or a combination of these symptoms.

Understanding a patient’s typical sleep–wake periods (on weekdays and weekends) and what the patient does both during the day (including work schedule, napping, and exercise) and in the hours leading up to bedtime and throughout the night is important. A detailed analysis of the patient’s thoughts and attitudes about sleep and maladaptive behavioral strategies is crucial to design effective treatment. Symptoms of any other sleep disorders that might impact sleep quality should be assessed, such as snoring, restless legs, apnea, pain, and parasomnias. A medication (prescription and over-the-counter) and substance use history (including time of day taken) is important and should include any caffeine, alcohol, or tobacco use. Table 51-1 lists medications and substances commonly associated with insomnia and Table 51-2 summarizes common comorbid medical conditions.

The most common assessment tools for insomnia include a sleep diary and questionnaires such as the Insomnia Severity Index and the Pittsburgh Sleep Quality Index. Overnight PSG may be warranted in cases in which a comorbid additional sleep disorder is considered or when treatment for insomnia has been unsuccessful. Actigraphy can be useful for establishing circadian disturbances that may be contributory as well as for tracking sleep–wake times and treatment response.

Pathophysiology

Insomnia is considered a disorder of hyperarousal, with patients demonstrating higher levels of cortisol, increased basal metabolic rates, and the presence of excessive beta or gamma activity on EEG.

The 3P (predisposing, precipitating, and perpetuating) model describes the development and maintenance of chronic insomnia. This model suggests that individuals may be vulnerable to developing insomnia based on predisposing factors that may be biologic (e.g., a diagnosis of chronic pain), psychologic (e.g., a family history of anxiety), or social (e.g., working shifts). Precipitating factors (e.g., a divorce or cancer diagnosis) may start an acute insomnia episode that is followed by behaviors that perpetuate a chronic insomnia, including worrying about sleep or consequences of poor sleep, spending more time in bed in an attempt to catch up on sleep, napping, and using more caffeine, alcohol, or over-the-counter medications.

Treatment

Treatment for insomnia generally involves nonpharmacologic and pharmacologic approaches. Unless a main, obvious underlying cause is found, treatment should focus on insomnia as a separate diagnosis to any other medical or psychiatric issues that may present simultaneously. Nonpharmacologic treatment is always preferred as a first-line intervention, though for many patients a combination of both behavioral and pharmacologic methods may be most beneficial.