SELF-ASSESSMENT

AND CME Postreading

Self-Assessment
and CME Test—Preferred
Responses
By D. Joanne Lynn, MD, FAAN; James W. M. Owens Jr, MD, PhD

SLEEP NEUROLOGY
Following are the preferred responses to the questions in the Postreading
Self-Assessment and CME Test in this Continuum issue. The preferred
response is followed by an explanation and a reference with which you
may seek more specific information. You are encouraged to review the
responses and explanations carefully to evaluate your general
understanding of the article topic. The comments and references included
with each question are intended to encourage independent study.

US PARTICIPANTS: Upon
completion of the Postreading Self-Assessment and
CME Test and issue evaluation online at continpub.com/CME, participants
may earn up to 20 AMA PRA Category 1 Credits™ toward SA-CME. US
participants have up to 3 years from the date of publication online to earn
SA-CME credits.

CANADIAN PARTICIPANTS: This

program is an Accredited Self-Assessment
Program (Section 3) as defined by the Maintenance of Certification
Program of the Royal College of Physicians and Surgeons of Canada and
approved by the University of Calgary Office of Continuing Medical
Education and Professional Development. Canadian participants should
visit MAINPORT (www.mainport.org) to record learning and outcomes.
Canadian participants can claim a maximum of 20 hours per issue (credits
are automatically calculated).

ARTICLE 1: NEUROBIOLOGY AND NEUROPROTECTIVE BENEFITS OF SLEEP

1 The preferred response is A (cholinergic). Acetylcholine production is highest

during wakefulness and rapid eye movement (REM) sleep. Dopaminergic effects
include alertness with DA1 stimulation and drowsiness with DA2 stimulation.
Glutamatergic activity is highest during wakefulness as are histaminergic systems.
For more information, refer to pages 852–853 of the Continuum article,
“Neurobiology and Neuroprotective Benefits of Sleep.”

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2 The preferred response is C (locus coeruleus). The wake-promoting effect of
orexinergic (hypocretinergic) neurons is most likely due to their dense
innervation of the noradrenergic locus coeruleus and the histaminergic
tuberomammillary nucleus. The dorsal raphe produces serotonin, a wake-
promoting monoamine, but is not densely innervated by orexinergic
(hypocretinergic) neurons. The cholinergic neurons of the lateral dorsal
tegmental nucleus are most active during wakefulness and rapid eye movement
(REM) sleep with little activity during non-REM sleep. The pedunculopontine
nucleus shows a similar pattern of activity. The wake-promoting neurons of
the parabrachial nucleus are glutamatergic. For more information, refer to
pages 854–855 of the Continuum article, “Neurobiology and Neuroprotective
Benefits of Sleep.”

3 The preferred response is C (parabrachial). The parabrachial nucleus is part of a

potent wake-promoting system, and lesions of this area produce prominent
impairments of consciousness. The lateral dorsal tegmental area, the
tuberomammillary nucleus, and the dorsal raphe nuclei produce wake-promoting
neurotransmitters, but not one of these systems is sufficient for producing
wakefulness, and impairment of just one system does not substantially reduce
wakefulness. The ventral lateral preoptic area is, together with the median
preoptic area, a primary source of sleep-promoting γ-aminobutyric acid–
mediated (GABA-ergic) activity. For more information, refer to page 858 of the
Continuum article, “Neurobiology and Neuroprotective Benefits of Sleep.”

4 The preferred response is A (adenosine). Adenosine is the most studied of

potential somnogens thought to mediate the homeostatic sleep-pressure
process. The other compounds listed, while involved in sleep or, as in the case
of cortisol, produced in a circadian pattern, are not thought to function as
somnogens. For more information, refer to page 861 of the Continuum article,
“Neurobiology and Neuroprotective Benefits of Sleep.”

ARTICLE 2: EVALUATING THE SLEEPY AND SLEEPLESS PATIENT

5 The preferred response is B (macroglossia). Various findings on physical

examination, including cervical and craniofacial abnormalities may indicate an
increased risk of obstructive sleep apnea. Macroglossia is one abnormality that
could lead to airway occlusion. Other findings include retrognathia (not
prognathia), micrognathia, enlarged tonsils or adenoids, obesity, an enlarged
neck circumference, and an increased respiratory rate. For more information,
refer to page 875 of the Continuum article “Evaluating the Sleepy and Sleepless
Patient.”

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POSTREADING TEST—PREFERRED RESPONSES

6 The preferred response is E (multiple sleep latency test). The multiple sleep
latency test is a key diagnostic examination to evaluate for narcolepsy. Patients
are given multiple opportunities to nap during the day during this test, and EEG is
recorded to document mean sleep latency and whether sleep-onset REM
periods occur. For more information, refer to page 881 of the Continuum article
“Evaluating the Sleepy and Sleepless Patient.”

7 The preferred response is B (moderate obstructive sleep apnea). The home

sleep apnea test is indicated for evaluation of adult patients at increased risk of
moderate to severe obstructive sleep apnea. The test has less sensitivity
compared with polysomnography and should not be used for a screening test
but only for patients thought to have a moderate or high risk of obstructive sleep
apnea. The home sleep apnea test is also not helpful for evaluation of patients
with pulmonary or neuromuscular conditions that might cause hypoventilation.
For more information, refer to pages 879–881 of the Continuum article
“Evaluating the Sleepy and Sleepless Patient.”

8 The preferred response is C (obstructive sleep apnea). Obstructive sleep apnea

is variably associated with mild to moderate bilateral morning headaches. The
occurrence of morning headaches is attributed to carbon dioxide retention and
compensatory brain vasodilation. For more information, refer to pages 873–874
of the Continuum article “Evaluating the Sleepy and Sleepless Patient.”

ARTICLE 3: CENTRAL DISORDERS OF HYPERSOMNOLENCE

9 The preferred response is A (cataplexy). Cataplexy is seen only in narcolepsy

type 1 while the other clinical features can be seen in either type of narcolepsy.
For more information, refer to page 891 of the Continuum article, “Central
Disorders of Hypersomnolence.”

10 The preferred response is B (idiopathic hypersomnia). This patient most likely

has idiopathic hypersomnia given his long sleep durations and unrefreshing
sleep with no other associated features. He does not have any of the
associated features of narcolepsy type 1 and, particularly, does not have
cataplexy. His long sleep durations would also be unusual for someone with
narcolepsy type 1. His hypersomnolence is persistent rather than episodic, as
would be seen in Kleine-Levin syndrome. His medical problems would not
explain his persistent excessive sleepiness. Finally, he sleeps more than he
should for his age and, therefore, does not have insufficient sleep syndrome.
For more information, refer to page 893 of the Continuum article, “Central
Disorders of Hypersomnolence.”

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11 The preferred response is A (lithium). This patient has Kleine-Levin syndrome,
and lithium has shown efficacy in reducing the duration, severity, and frequency
of attacks. Methylphenidate has limited effectiveness in mitigating sleepiness
during an attack. Sodium oxybate is used to treat narcolepsy type 1. For more
information, refer to page 904 of the Continuum article, “Central Disorders of
Hypersomnolence.”

12 The preferred response is E (narcolepsy type 1). Scheduled naps and regular
nocturnal sleep can provide significant benefit for patients with narcolepsy
type 1. Naps are not refreshing or generally helpful for patients with idiopathic
hypersomnia and can be counterproductive in patients with chronic insomnia or
insufficient sleep syndrome as they tend to interfere with consolidated
nocturnal sleep. Kleine-Levin syndrome is characterized by dramatic
hypersomnolence, and adding naps to this would not prove helpful. For more
information, refer to pages 900–901 of the Continuum article, “Central Disorders
of Hypersomnolence.”

ARTICLE 4: OBSTRUCTIVE SLEEP APNEA

13 The preferred response is D (insomnia). Sex differences exist in the

presentation and initial symptoms for patients with obstructive sleep apnea
(OSA). Women with OSA are more likely to report nonspecific symptoms of
sleep-disordered breathing such as headache, fatigue, depression, anxiety, and
insomnia and are less likely to present with the classic complaints of snoring,
snorting, gasping, and apneas compared with men with a similar severity of
disease. For more information, refer to page 909 of the Continuum article
“Obstructive Sleep Apnea.”

14 The preferred response is E (scalloping). Scalloping of the tongue suggests that

the tongue is too large for the mouth and is indented by the patient’s teeth. A
large tongue can encroach on the posterior pharyngeal space. Fissuring can be
a normal variant or suggest a nutritional deficiency. Geographic tongue is a
benign condition of smooth red patches with contiguous white borders.
Leukoplakia is a hypertrophic cell response, often in response to an irritant. It
can be a precancerous condition. Oral lichen planus consists of raised white
lines on the tongue that have a lacey appearance also related to chronic
irritation and often self-limited. For more information, refer to page 911 of the
Continuum article “Obstructive Sleep Apnea.”

15 The preferred response is D (respiratory arousals on EEG). The apnea-

hypopnea index assesses obstructive sleep apnea severity by measuring
the number of apneas and hypopneas divided by hours of sleep in a sleep
study. The respiratory disturbance index includes respiratory event-related

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POSTREADING TEST—PREFERRED RESPONSES

arousals as captured on EEG in addition to apneas and hypopneas. For more

information, refer to pages 915–916 of the Continuum article “Obstructive Sleep
Apnea.”

16 The preferred response is E (uvulopalatopharyngoplasty). When more

conservative measures such as weight loss, oral appliance therapy, and
continuous positive airway pressure are not helpful, various surgical approaches
to the management of obstructive sleep apnea (OSA) may be tried.
Uvulopalatopharyngoplasty to open the upper airway is the most commonly
performed surgical procedure for OSA and is variably effective. For more
information, refer to pages 919–920 of the Continuum article “Obstructive Sleep
Apnea.”

ARTICLE 5: RAPID EYE MOVEMENT SLEEP BEHAVIOR DISORDER AND

OTHER RAPID EYE MOVEMENT PARASOMNIAS

17 The preferred response is D (dementia with Lewy bodies). Rapid eye

movement (REM) sleep behavior disorder (RBD) is a syndrome that represents
the prodrome of one of several neurodegenerative disorders of α-synuclein
pathology in the majority of cases. This group of disorders includes Parkinson
disease, dementia with Lewy bodies, and multiple system atrophy. Amyotrophic
lateral sclerosis is also associated with an increased prevalence of RBD but at a
lower rate compared with the α-synuclein disorders. For more information,
refer to page 941 of the Continuum article “Rapid Eye Movement Sleep Behavior
Disorder and Other Rapid Eye Movement Parasomnias.”

18 The preferred response is C (consolidation of emotionally laden memories).

One function of rapid eye movement (REM) sleep is the consolidation of
emotionally laden memories with strengthening of the synaptic connections
between a memory trace and the amygdala. This provides salience to
experiences that promote behavioral vigilance and skills for survival and social
interactions. The other choices listed are functions of non-REM sleep. For more
information, refer to page 932 of the Continuum article “Rapid Eye Movement
Sleep Behavior Disorder and Other Rapid Eye Movement Parasomnias.”

19 The preferred response is E (melatonin). Exogenous melatonin, which binds to

M1 and M2 receptors, has been shown to be efficacious for the treatment of
rapid eye movement sleep behavior disorder by decreasing both dream
enactment and sleep-related injury. Side effects are generally tolerable and
include abdominal discomfort, vivid dreams, and sleep fragmentation.
Clonazepam is another first-line pharmacologic treatment but is often not
tolerated due to side effects of sedation, imbalance, and cognitive
disturbances, especially in older adults or those with concomitant α-synuclein

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 pathology. For more information, refer to page 938 of the Continuum article
“Rapid Eye Movement Sleep Behavior Disorder and Other Rapid Eye Movement
Parasomnias.”

20 The preferred response is E (non–tremor-predominant presentation).

Approximately 20% to 40% of patients with Parkinson disease have rapid eye
movement (REM) sleep behavior disorder (RBD). The presence of RBD predicts
a non–tremor-predominant presentation. It is also associated with an atypical,
more aggressive clinical course with more severe bradykinesia, motor
fluctuations, autonomic instability, hallucinations, and cognitive decline. For
more information, refer to pages 941–942 of the Continuum article “Rapid Eye
Movement Sleep Behavior Disorder and Other Rapid Eye Movement
Parasomnias.”

ARTICLE 6: PARASOMNIAS OCCURRING IN NON–RAPID EYE MOVEMENT

SLEEP

21 The preferred response is C (nocturnal panic attacks). This patient’s episodes

are most consistent with nocturnal panic attacks. In particular, the fact that
she has prominent autonomic activation together with preservation of
responsiveness during the event with full wakefulness before returning to sleep
is highly suggestive of this diagnosis. Her history of generalized anxiety disorder
is supportive. Sleep terrors would have the autonomic component without
responsivity or full wakefulness. Nightmares would be associated with vivid
dream mentation. Rapid eye movement (REM) sleep behavior disorder is
characterized by vocalization, flailing of the arms, and kicking. For more
information, refer to page 954 of the Continuum article “Parasomnias Occurring
in Non–Rapid Eye Movement Sleep.”

22 The preferred response is A (clonazepam). While no randomized controlled

trials have been performed, clonazepam has long been used to decrease the
frequency of non–rapid eye movement (REM) parasomnias. Haloperidol,
sodium oxybate, and zolpidem have been implicated in precipitating
sleepwalking episodes. Trazodone is not indicated for the treatment of
non-REM parasomnias. For more information, refer to page 955 of the
Continuum article “Parasomnias Occurring in Non–Rapid Eye Movement Sleep.”

23 The preferred response is D (seizure). This patient’s nocturnal event is most

likely to be a seizure given that it is brief, stereotyped, and reliably associated
with enuresis and a brief arousal and occurs at any point during the night. The
symptomatology of the event is also very suggestive of a motor seizure,
although significant motor behavior can occur with rhythmic movement
disorder, rapid eye movement (REM) sleep behavior disorder, and sleep

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POSTREADING TEST—PREFERRED RESPONSES

terrors. A confusional arousal would be motorically quiet. For more information,

refer to page 953 of the Continuum article “Parasomnias Occurring in
Non–Rapid Eye Movement Sleep.”

ARTICLE 7: RESTLESS LEGS SYNDROME AND OTHER COMMON

SLEEP-RELATED MOVEMENT DISORDERS

24 The preferred response is C (stop metoclopramide). Before initiating

symptomatic therapy, it would be prudent to first eliminate potential
exacerbating factors including, in this case, metoclopramide. For more
information, refer to page 970 of the Continuum article, “Restless Legs
Syndrome and Other Common Sleep-Related Movement Disorders.”

25 The preferred response is C (IV iron). Given this patient’s clinically significant
restless legs syndrome, as well as worsening hypertension and relatively low
serum ferritin level and transferrin saturation, IV iron would be the best
treatment at this point. IV iron is recommended over oral iron supplementation
when the serum ferritin level is less than 100 ng/mL. While pramipexole,
clonazepam, and particularly gabapentin are symptomatic treatments that may
prove helpful, intervention with iron would be the preferred option, balancing
efficacy and potential side effects. For more information, refer to page 973 of
the Continuum article, “Restless Legs Syndrome and Other Common
Sleep-Related Movement Disorders.”

26 The preferred response is A (obstructive sleep apnea). While this patient has
restless legs syndrome and periodic limb movements, his primary sleep
disorder is obstructive sleep apnea given his apnea-hypopnea index.
Obstructive sleep apnea can be associated with periodic limb movements as
can restless legs syndrome, although neither invariably so. For more
information, refer to page 967 of the Continuum article, “Restless Legs
Syndrome and Other Common Sleep-Related Movement Disorders.”

27 The preferred response is A (clonazepam). This patient has sleep-related

rhythmic movement disorder, and the most commonly used treatment for this
condition, when treatment is indicated, is clonazepam. For more information,
refer to pages 983–984 of the Continuum article, “Restless Legs Syndrome and
Other Common Sleep-Related Movement Disorders.”

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ARTICLE 8: CIRCADIAN RHYTHM SLEEP-WAKE DISORDERS

28 The preferred response is E (tasimelteon). This man’s sleep problem is

consistent with non–24-hour sleep-wake disorder. Melatonin is a useful
treatment but is not specifically US Food and Drug Administration (FDA)
approved for this indication. Tasimelteon is a melatonin receptor agonist that is
approved for use in the treatment of circadian rhythm sleep-wake disorders.
Caffeine has not been demonstrated to help with entraining non–24-hour
sleep-wake disorder. Lemborexant is an orexin (hypocretin) receptor
antagonist for the treatment of insomnia. Modafinil helps with alertness. For
more information, refer to pages 996–997 of the Continuum article “Circadian
Rhythm Sleep-Wake Disorders.”

29 The preferred response is E (shift work disorder). Exposure to rotating shift

work has been associated with an increased risk of breast cancer with the
resultant declaration of shift work as a potential carcinogen by the World
Health Organization in 2007. Individuals vary significantly in their susceptibility
to sleep loss with shift work, but the risk of cardiometabolic disease with shift
work is also increased. For more information, refer to page 997 of the
Continuum article “Circadian Rhythm Sleep-Wake Disorders.”

30 The preferred response is D (suprachiasmatic). The suprachiasmatic nucleus of

the anterior hypothalamus is the principal generator of circadian rhythms in the
mammalian brain. Efferent pathways from the suprachiasmatic nucleus
regulate numerous physiologic circadian rhythms affecting many aspects of
physiology including core body temperature and endocrine, autonomic, and
behavioral functions. For more information, refer to page 998 of the
Continuum article “Circadian Rhythm Sleep-Wake Disorders.”

ARTICLE 9: INSOMNIA

31 The preferred response is B (cognitive-behavioral therapy). Cognitive-

behavioral therapy is considered the gold standard in the treatment of
insomnia, although the other items can be considered in the right clinical
context. For more information, refer to page 1007 of the Continuum article,
“Insomnia.”

32 The preferred response is C (hypnotherapy). Unlike other integrative

approaches, hypnotherapy can be associated with headache, drowsiness,
false memories, and strong emotions due to stressful situations from previous
events. For more information, refer to pages 1010–1011 of the Continuum article,
“Insomnia.”

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POSTREADING TEST—PREFERRED RESPONSES

33 The preferred response is A (autonomous sensory meridian response).

Autonomous sensory meridian response aims at producing a tinglinglike
sensation across the scalp and back of the neck in response to specific
auditory and visual stimuli. Healing touch, Qigong, and Reiki are energy healing
modalities, whereas tactile therapy is, like autonomous sensory meridian
response, a sleep aid strategy aimed at producing a state of relaxation (in the
case of tactile therapy, using physical touch with various objects). For more
information, refer to page 1012 of the Continuum article, “Insomnia.”

ARTICLE 10: SLEEP IN PATIENTS WITH NEUROLOGIC DISEASE

34 The preferred response is D (suprachiasmatic nuclei). The suprachiasmatic

nuclei are the primary pacemakers of the circadian rhythms. Degenerative loss
of neuronal populations including those that express arginine vasopressin or
vasoactive intestinal peptide in Alzheimer disease is associated with irregular
sleep rhythms and “sundowning” behaviors. For more information, refer to
pages 1020–1021 of the Continuum article “Sleep in Patients with Neurologic
Disease.”

35 The preferred response is C (hyposmia). The majority of patients with rapid eye
movement (REM) sleep behavior disorder will eventually develop an
α-synucleinopathy such as Parkinson disease or dementia with Lewy bodies. The
presence of hyposmia is a concomitant factor that is associated with an increased
risk of conversion from idiopathic REM sleep behavior disorder to Parkinson
disease. This reflects the fact that the process of α-synuclein degeneration begins
in the gut and olfactory bulb and then spreads more rostrally and centrally in the
nervous system through the vagus and limbic circuits, respectively. Other risk
factors include older age, family history of Parkinson disease, and orthostatic
hypotension. For more information, refer to pages 1021–1022 of the Continuum
article “Sleep in Patients with Neurologic Disease.”

36 The preferred response is C (Huntington disease). Sleep provides a quiescent

period for most abnormal movements associated with movement disorders.
However, the choreoathetosis of Huntington disease typically persists during
sleep. The other movement disorder that typically persists throughout sleep is
palatal myoclonus. For more information, refer to page 1023 of the Continuum
article “Sleep in Patients with Neurologic Disease.”

ARTICLE 11: SLEEP-WAKE DISORDERS IN CHILDHOOD

37 The preferred response is D (paradoxical reaction). This patient experienced a

paradoxical reaction to the hypnotic medication associated with a low dose.

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 Insufficient dosing can contribute to a tendency for paradoxical reactions. For
more information, refer to pages 1040–1041 of the Continuum article,
“Sleep-Wake Disorders in Childhood.”

38 The preferred response is E (restless sleep disorder). The best diagnosis would
be restless sleep disorder, given her description as an active sleeper without
evidence of restless legs syndrome or obstructive sleep apnea. Her occasional
parasomnias are likely indicators of fragmented sleep rather than primary
problems. She obtains sufficient sleep for her age and, therefore, does not
meet the criteria for insufficient sleep or hypersomnia. For more information,
refer to page 1048 of the Continuum article, “Sleep-Wake Disorders in
Childhood.”

39 The preferred response is B (clonazepam). Of the medications listed, only

clonazepam would be reasonable to consider for the treatment of frequent or
dangerous parasomnias. Sodium oxybate, fluoxetine, and baclofen are used in
the treatment of narcolepsy whereas gabapentin is used to treat restless legs
syndrome. For more information, refer to page 1052 of the Continuum article,
“Sleep-Wake Disorders in Childhood.”

40 The preferred response is A (beta-blocker in the morning). A beta-blocker

administered in the morning can suppress abnormal melatonin secretion during
the daytime and reduce daytime sleep attacks. For more information, refer to
page 1059 of the Continuum article, “Sleep-Wake Disorders in Childhood.”

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