Sanjeev V. Kothare, Rebecca Quattrucci Scott (Eds.) - Sleep Disorders in Adolescents - A Clinical Casebook-Springer International Publishing (2017)

Sanjeev V.
Kothare
Rebecca Quattrucci Scott Editors
Sleep Disorders
in Adolescents
A Clinical Casebook
123
Sleep Disorders in Adolescents
Sanjeev V. Kothare
Rebecca Quattrucci Scott
Editors
Sleep Disorders
in Adolescents
A Clinical Casebook
Editors
Sanjeev V. Kothare Rebecca Quattrucci Scott
Department of Neurology NYU Comprehensive Epilepsy
Director, Pediatric Sleep Program Center-Sleep Center
NYU Comprehensive Sleep Department of Neurology
Disorders Center NYU Langone Medical Center
Professor, Department of New York, NY, USA
Neurology
NYU Langone Medical Center
and NYU School of Medicine
New York, NY, USA
ISBN 978-3-319-41741-7 ISBN 978-3-319-41742-4 (eBook)

DOI 10.1007/978-3-319-41742-4
Library of Congress Control Number: 2016950520
© Springer International Publishing Switzerland 2017

This work is subject to copyright. All rights are reserved by the Publisher, whether
the whole or part of the material is concerned, specifically the rights of translation,
reprinting, reuse of illustrations, recitation, broadcasting, reproduction on
microfilms or in any other physical way, and transmission or information storage
and retrieval, electronic adaptation, computer software, or by similar or dissimilar
methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks,
etc. in this publication does not imply, even in the absence of a specific statement,
that such names are exempt from the relevant protective laws and regulations and
therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and
information in this book are believed to be true and accurate at the date of
publication. Neither the publisher nor the authors or the editors give a warranty,
express or implied, with respect to the material contained herein or for any errors
or omissions that may have been made.
Printed on acid-free paper
This Springer imprint is published by Springer Nature

The registered company is Springer International Publishing AG Switzerland
Preface
We would like to dedicate this book to all the patients and their
families who taught us even more than our textbooks. We have
penned these experiences in this book to enrich your experience in
similar situations, and we hope that this will enable you to treat
your patients even more effectively. We would also like to
acknowledge all the fellows whom we have trained over the years
and who taught us to introspect on how we manage our patients to
their best satisfaction. Several of these trainees have contributed to
chapters in this book. Finally we would like to acknowledge our
families, for their understanding for being away from them as we
worked on this book.
New York, NY, USA Sanjeev V. Kothare

Rebecca Quattrucci Scott
v
Contents
1 Introduction .................................................................. 1
Sanjeev V. Kothare and Rebecca Quattrucci Scott
2 Delayed Sleep Phase Syndrome .................................. 7
Sasha D. Jaquez, Tushar P. Thakre,
and Jyoti Krishna
3 Restless Legs Syndrome............................................... 27
Mandana Mahmoudi and Sanjeev V. Kothare
4 Obstructive Sleep Apnea in Adolescence ................... 45
Stacey Gunn and Umakanth A. Khatwa
5 Narcolepsy in Adolescence .......................................... 61
Anne Marie Morse and Sanjeev V. Kothare
6 Parasomnias in Adolescents ........................................ 79
Joseph Kaleyias, Rebecca Quattrucci Scott,
and Sanjeev V. Kothare
7 Sleep in Adolescents with Psychiatric Disorders....... 95
Ujjwal Ramtekkar and Anna Ivanenko
8 Medical Disorders ........................................................ 119
Vicky Chiang and Alcibiades J. Rodriguez
9 Brain Tumors................................................................ 133
Danielle M. Graef and Valerie McLaughlin Crabtree
10 Insomnia........................................................................ 155
Mariya Narizhnaya and Matthew R. Ebben
vii
viii Contents
11 Epilepsy and Sleep in Adolescents .............................. 173

Sejal V. Jain and Sanjeev V. Kothare
12 Traumatic Brain Injury ............................................... 187
Kanwaljit Singh and Sanjeev V. Kothare
Index ...................................................................................... 203

Contributors
Vicky Chiang, B.S. Department of Neurology, New York

University Medical School, La Mirada, CA, USA
Valerie McLaughlin Crabtree, Ph.D. Department of Psychology,
St. Jude Children’s Research Hospital, Memphis, TN, USA
Matthew R. Ebben, Ph.D. Department of Neurology, Weill
Cornell Medical College, New York, NY, USA
Danielle M. Graef, Ph.D. Department of Psychology, St. Jude
Children’s Research Hospital, Memphis, TN, USA
Stacey Gunn, M.D. Division of Pulmonary, Critical Care and
Sleep, Beth Israel Deaconess Medical Center, Boston, MA, USA
Anna Ivanenko, M.D., Ph.D. Department of Psychiatry and
Behavioral Sciences, Feinberg School of Medicine, Northwestern
University, Division of Child and Adolescent Psychiatry, Ann and
Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA
Sejal V. Jain, M.D. Division of Neurology and Pediatrics, Banner
University Medical Center, Tucson, AZ, USA
Sasha D. Jaquez, Ph.D. Pulmonary Medicine and Pediatric
Psychiatry/Psychology, Northeast Ohio Medical University and
Akron Children’s Hospital, Akron, OH, USA
Joseph Kaleyias, M.D., Ph.D. Department of Paediatrics,
Colchester University Hospital NHS Foundation Trust, Colchester,
Essex, UK
ix
x Contributors
Umakanth A. Khatwa, M.D. Division of Respiratory Diseases,

Department of Medicine, Boston Children’s Hospital, Boston,
MA, USA
Sanjeev V. Kothare, M.D. Department of Neurology, NYU
Comprehensive Sleep Disorders Center, NYU Langone Medical
Center and NYU School of Medicine, New York, NY, USA
Jyoti Krishna, M.D. Pulmonary Medicine, North East Ohio Medical
University and Akron Children’s Hospital, Akron, OH, USA
Mandana Mahmoudi, M.D. Pulmonary, Critical Care, and Sleep
Medicine, New York University Langone Medical Center, New
York, NY, USA
Anne Marie Morse, M.D. Division of Sleep Medicine—
Neurology, Montefiore Medical Center, Bronx, NY, USA
Mariya Narizhnaya, M.A. Department of Neurology, Weill Cornell
Medical College, New York, NY, USA
Ujjwal Ramtekkar, M.D. Division of Psychiatry, Compass
Health Network, St. Louis, Wentzville, MO, USA
Alcibiades J. Rodriguez, M.D. Department of Neurology, New
York University Medical School, New York, NY, USA
Rebecca Quattrucci Scott, Ph.D. Department of Neurology,
NYU Langone Medical Center, NYU Comprehensive Epilepsy
Center-Sleep Center, New York, NY, USA
Kanwaljit Singh, M.D. Department of Pediatrics (Neurology),
University of Massachusetts Medical School, Worcester, MA, USA
Tushar P. Thakre, M.D., Ph.D. VCU Center for Sleep Medicine,
Virginia Commonwealth University, Richmond, VA, USA
Introduction
1
Sanjeev V. Kothare and Rebecca Quattrucci
Scott
It is a known fact that sleep is vital for physical, cognitive and

emotional health and well-being [1]. Over the past decade a myriad
of studies have linked insufficient or poor quality sleep to a number
of negative outcomes, including obesity [2, 3], diabetes [4, 5], car-
diovascular disease [5], Alzheimer’s disease [6], cognitive impair-
ment [6], lapses in memory and attention [7], impaired performance
[8, 9], sleepiness [8, 9], tiredness [8, 9], and increased depression
and anxiety [10, 11]. The Center for Disease Control recently
stated that insufficient sleep is a public health epidemic [12].
And yet millions of people still do not get enough sleep. This is
especially true among adolescences.
The National Sleep Foundation recommends that teenagers
need 8–10 h of sleep a night for optimal function; however,
research suggests that <15–20 % of adolescents get the recom-
mended amount on school nights [13]. Lifestyle/behavioral/
environmental factors, such as homework, part-time jobs, extra-
curricular and social activities, and excessive screen time, contrib-
ute to the growing sleep debt in this age group [13]. Additionally,
adolescents have a natural biological shift toward later bedtimes
and wake times, adding insult to injury.
S.V. Kothare, M.D. (*) • R. Quattrucci Scott, Ph.D.

Department of Neurology, NYU Langone Medical Center and NYU
School of Medicine, 223 East 34th Street, New York, NY 10016, USA
e-mail: sanjeev.kothare@nyumc.org; rebecca.scott@nyumc.org
© Springer International Publishing Switzerland 2017 1

S.V. Kothare, R. Quattrucci Scott (eds.), Sleep Disorders
in Adolescents, DOI 10.1007/978-3-319-41742-4_1
2 S.V. Kothare and R. Quattrucci Scott
As with adults, inadequate sleep in teenagers has significant and

widespread ramifications across several domains. For example:
Physiological: Sleep deprived teens are at increased risk for obe-
sity, diabetes, and hypertension; have an increased incidence of
headaches, gastrointestinal disturbance, backaches, and muscle
tension; report lower energy and greater fatigue; and are less likely
to engage in health-related behaviors, such as taking responsibility
for their health, adopting a healthy diet, implementing regular
exercise, and practicing stress management [14].
Cognitive/academic performance: Sleep deprivation in teens is
associated with cognitive impairment; difficulties with focus,
memory, and attention; impaired decision-making; decreased
reaction time; impaired academic performance; and decreased cre-
ativity [14, 15].
Psychological/emotional: Sleep deprivation in teens is associated
with increased alcohol and drug use, aggression, irritability, risky
behaviors, anxiety, depression, suicidal thoughts and behaviors,
poor impulse control and social skills, and low motivation [14–17].
In addition to the above biopsychosocial factors contributing to
insufficient sleep in this population, there are a number of treatable
sleep disorders that could also be contributing. This casebook on
adolescent sleep medicine is designed to present a comprehensive
review of common, yet sometimes overlooked, sleep problems in
adolescents. Each chapter addresses a unique, though not uncom-
mon, sleep disorder in teenagers through illustrative cases, rele-
vant literature, and pearls of wisdom for the practicing sleep
specialist or any other practitioner involved in the care of
adolescents.
In Chap. 2, four detailed and distinct cases of Delayed Sleep-
Wake Phase Disorder (DSWPD), a circadian rhythm disorder that
often gives the appearance of sleep-onset insomnia but that is, more
accurately, a delay in the ability to fall asleep at conventional times,
are presented. Among disorders of circadian rhythm, DSWPD is
common in adolescents and young adults, a population that already
has a natural endogenous shift towards later bedtimes. Genetic, envi-
ronmental, social, and behavioral factors that can contribute to the
development and perpetuation of this disorder are discussed at
1 Introduction 3
length. Comprehensive evaluation and treatment plans, including the

use of sleep diaries, actigraphy, light therapy, melatonin, and a
graphic display of phase shifting principles, are also provided.
Chap. 3 depicts three cases of restless legs syndrome (RLS),
an often under-recognized neurologic sensorimotor disorder,
affecting approximately 2 % of male and female adolescents. RLS
is characterized by an urge to move the legs, usually associated
with leg discomfort. The symptoms occur at rest, are relieved by
movement, and are most severe in the evening and at night.
Common mimics of RLS are described in detail, as are non-phar-
macological and pharmacological approaches to management.
In Chap. 4, three cases of adolescent obstructive sleep apnea
(OSA) are reviewed. While OSA has historically been considered
a disorder most common among overweight adult males, adoles-
cent sleep apnea has become increasingly more common with the
rise in obesity rates. Management of these patients is less straight-
forward than management in younger children or older adults, as
there are substantial rates of treatment failure following adenoton-
sillectomy, which remains the first-line treatment approach.
Second-line therapy for residual OSA is continuous positive air-
way pressure therapy (CPAP), which can be poorly tolerated in
this age-group. This chapter provides an in-depth discussion of the
physical exam findings, comorbid medical conditions, and night-
time and daytime features associated with this condition, as well as
factors associated with a high risk of residual OSA in adolescents.
Strategies to troubleshoot commonly encountered problems with
CPAP management are also presented as is drug-induced sleep
endoscopy (DISE), a tool that can help identify common sites of
airway obstruction in this population and guide surgical planning.
Chap. 5 presents four cases of Narcolepsy, a chronic neuro-
logic disorder that causes a dysregulation of the sleep-wake cycle,
each with unique features and points of consideration regarding
associated symptoms, evaluation, diagnosis, and management.
Additionally, this chapter includes tables of common descriptors
of cataplexy, a distinct associated symptom of narcolepsy; ques-
tions that may be useful in identifying these symptoms; sugges-
tions to help patients maintain a safe sleep environment; and a
comprehensive list of medications used to treat this disorder.
Chap. 6 reviews three cases of either non-REM or REM

Parasomnias, which are undesirable or unpleasant physical events
or experiences that occur during entry into sleep, within sleep, or
during arousal from deep sleep. They encompass abnormal com-
plex movements, behaviors, emotions, perceptions, dreams, and
autonomic activity emanating from or associated with sleep and
that can result in sleep disruption, adverse health effects, untoward
psychosocial effects, and/or resulting injuries. Characteristic fea-
tures of various manifestations of parasomnias, features to con-
sider for the differential diagnosis between parasomnias and
nocturnal frontal lobe epilepsy, and a schematic regarding evalua-
tion and treatment are also presented.
In Chap. 7, two clinical cases demonstrate the complex rela-
tionship between sleep and emotional regulation in adolescents.
These cases provide a detailed review of clinical features of major
depression and PTSD along with the differential diagnosis as it
pertains to sleep disturbances that are typically seen in youth with
early onset depression and PTSD. Numerous studies have reported
subjective sleep symptoms in adolescents with depressive disor-
ders and anxiety and there have been several studies to identify the
objective markers of depression using sleep measures such as
polysomnography and actigraphy. This chapter also provides a
review of the literature on the phenomenology of sleep disorders in
adolescents with depressive disorder and PTSD and presents
research-based and clinically guided recommendations for the
evaluation and treatment of sleep disorders.
In Chap. 8, three cases exemplify how sleep disorders can com-
monly coexist with medical disorders. As the human body is not
an isolated entity, sleep disturbances affect control and outcome of
different medical disorders and medical disorders play an important
role in sleep quality and quantity. This chapter presents three very
common medical disorders (asthma, hypothyroidism, and migraine)
in children and adolescents that may affect sleep and vice versa.
Chap. 9 consists of comprehensive sleep and cognitive evalua-
tions over a 21-month period of a 12-year-old male who was diag-
nosed with and treated for a brain tumor (craniopharyngioma)
and for related complications that included several endocrinopa-
thies and excessive daytime sleepiness (EDS) with a resulting
diagnosis of narcolepsy without cataplexy. The clinical outcomes
1 Introduction 5
following a pharmacological intervention for his narcolepsy are

presented. Adolescents who have or have been treated for a brain
tumor are vulnerable to sleep concerns, including excessive day-
time sleepiness. This case highlights the importance of objectively
evaluating sleepiness in adolescents with brain tumors (particu-
larly those involving the hypothalamus), the importance of closely
monitoring cognitive and academic performance, and the impor-
tant role of medication management in impacting daytime func-
tioning in this vulnerable population.
Chap. 10 reviews a case of a 19-year-old female college student
who complains of Insomnia, characterized by trouble falling
asleep and frequent awakenings throughout the night, daytime
tiredness, and trouble concentrating in class. She participated in
six weekly cognitive behavioral therapy sessions for insomnia,
which included nightly monitoring through a sleep diary, cognitive
restructuring, sleep restriction, stimulus control, and relaxation
techniques. Each of these approaches is discussed in detail.
Chap. 11 introduces three cases of Epilepsy, a neurological
condition not uncommon in adolescents. Given that sleep disor-
ders are common in patients with epilepsy, there is an increased
likelihood that a sleep specialist may be involved in overall evalu-
ation, management, and care of patients with these comorbid con-
ditions. The most commonly described sleep disorder in patients
with epilepsy is obstructive sleep apnea, though forms of insomnia
and hypersomnia tend to be common as well. This chapter presents
infrequently described but important associations and coexistence
of sleep disorders with common epilepsy syndromes.
Chap. 12 presents three case studies discussing the spectrum of
sleep disorders associated with Traumatic Brain Injury (TBI),
followed by a general discussion of the spectrum of sleep disorders
in TBI, proposed mechanisms, and clinical approach to diagnosis
and management of these disorders. Treatment considerations for
sleep disorders in patients following traumatic brain injury are also
presented in detail. The prevalence, recognition, and awareness of
concussion have been on the rise in recent years in teenagers par-
ticipating in impact sports. What is under-recognized is the extent
of sleep problems seen in this population. Issues around forced bed
rest have also been addressed in this chapter.
References
1. Brand S, Kirov R. Sleep and its importance in adolescence and in common
adolescent somatic and psychiatric conditions. Int J Gen Med. 2011;4:
425–42.
2. Beccuti G, Pannain S. Sleep and obesity. Curr Opin Clin Nutr Metab Care.
2011;14(4):402–12.
3. Gupta N, et al. Is obesity associated with poor quality sleep in adoles-
cents? Am J Hum Biol. 2002;14(6):762–8.
4. Lou P, et al. Relation of sleep quality and sleep duration to type 2 diabetes:
a population-based cross-sectional. BMJ Open. 2012;2, e000956.
5. Buxton O, Marcelli E. Short and long sleep are positively associated with
obesity, diabetes, hypertension, and cardiovascular disease among adults
in the United States. Soc Sci Med. 2010;71(5):1027–36.
6. McEwen B. Sleep deprivation as a neurobiologic and physiologic stressor:
allostasis and allostatic load. Metabolism. 2006;55(2):S20–3.
7. Durmer JS, Dinges DF. Neurocognitive consequences of sleep depriva-
tion. Semin Neurol. 2005;25:117–29.
8. Basner M, et al. Sleep deprivation and neurobehavioral dynamics. Curr
Opin Neurobiol. 2013;23(5):854–63.
9. Belenky G, et al. Patterns of performance degradation and restoration dur-
ing sleep restriction and subsequent recovery: a sleep dose-response study.
J Sleep Res. 2003;12:1–12.
10. Shochat T, et al. Functional consequences of inadequate sleep in adoles-
cents: a systematic review. Sleep Med Rev. 2014;18(1):75–87.
11. Sarchiapone M, et al. Hours of sleep in adolescents and its association
with anxiety, emotional concerns, and suicidal ideation. Sleep Med.
2014;15(2):248–54.
12. National Centers for Disease Control and Prevention. Insufficient sleep is
a public health problem. Updated September/2015. http://www.cdc.gov/
features/dssleep/.
13. National Sleep Foundation. https://sleepfoundation.org/sleep-topics/teens-
and-sleep.
14. Keyes K, et al. The great sleep recession: changes in sleep duration among
US adolescents, 1991–2012. Pediatrics. 2015;135(3):460–8.
15. Wolfson AR, Carskadon MA. Understanding adolescents’ sleep patterns
and school performance: a critical appraisal. Sleep Med Rev. 2003;7(6):
491–506.
16. Smaldone A, et al. Sleepless in America: inadequate sleep and relation-
ships to health and well-being of our nation’s children. Pediatrics.
2007;119 Suppl 1:S29–37.
17. Dahl R, Lewin D. Pathways to adolescent health sleep regulation and
behavior. J Adolesc Health. 2002;31(6):S175–84.
Delayed Sleep Phase
Syndrome 2
Sasha D. Jaquez, Tushar P. Thakre,
and Jyoti Krishna
Abbreviations
AASM American Academy of Sleep Medicine

ADHD Attention-deficit/hyperactivity disorder
CBTmin Core body temperature minimum
CR Circadian rhythm
CRSWD Circadian rhythm sleep-wake disorders
DLMO Dim light melatonin onset
DLMOff Dim light melatonin offset
DSWPD Delayed sleep-wake phase disorder
S.D. Jaquez, Ph.D.

Pulmonary Medicine and Pediatric Psychiatry/Psychology,
Northeast Ohio Medical University and Akron Children’s Hospital,
300 Locust Street, Akron, OH 44302, USA
e-mail: sdjaquez@seton.org
T.P. Thakre, M.D., Ph.D.
VCU Center for Sleep Medicine, Virginia Commonwealth University,
2529 Professional Road, Richmond, VA 23235, USA
e-mail: tushar.thakre@vcuhealth.org
J. Krishna, M.D. ()
Pulmonary Medicine, North East Ohio Medical University
and Akron Children’s Hospital,
215 W. Bowery Street, Akron, OH 44308, USA
e-mail: jkrishna@chmca.org

8 S.D. Jaquez et al.
EDS Excessive daytime sleepiness

H Hour
LD Light-dark
PRC Phase response curve
PSG Polysomnography
Case Presentation 1
Hannah is a 17-year-old female presenting to the sleep clinic with

complaints of difficulty initiating sleep and excessive daytime
sleepiness (EDS). Hannah and her mother recall that Hannah has
always been a “bad sleeper” but that the problem has gradually
been worsening, particularly over the past several years. No con-
cerns of frequent leg movements, nightmares, sleep terrors, respi-
ratory pauses, snoring, or nighttime awakenings are reported. She
has previous diagnoses of depression and attention-deficit/hyper-
activity disorder (ADHD). Her ADHD is managed with medica-
tion and her depression is managed with a combination of
medication and cognitive-behavioral therapy. Both are well con-
trolled at the time of the appointment.
Hannah is a junior at a local high school and reports a gradual
decline in grades. She states she falls asleep multiple times a week
at school and often will miss her morning classes due to lack of
alertness after waking. Hannah reports an average bedtime of
10:00 pm with an estimated sleep onset between 2:00 and 3:00 am.
She sets an alarm to wake around 5:30 am for school, but hits the
snooze button repeatedly until around 6:50 am, and reports still
being sleepy and having difficulty getting out of bed. She admits
to occasionally taking naps after school. On weekends, Hannah
states she goes to bed around 2:00–2:30 am, initiates sleep around
3:00 am, and wakes between 11:00 am and 12:00 pm. She reports
some improvement in her symptoms of EDS during the weekend.
However, during longer breaks from school (e.g., winter, summer)
she notes significant improvements in her symptoms of EDS when
she is able to consistently delay her sleep schedule.
Nothing notable is found on her physical exam. Specifically,
there is no tonsillomegaly or obesity. Mood and interactions appear
unremarkable.
2 Delayed Sleep Phase Syndrome 9
Discussion
In the patient above, a thorough sleep history and sleep logs (see
Fig. 2.1) would be needed to properly diagnose her sleep con-
cerns. Lack of snoring and leg symptoms as well as a normal
physical examination make the diagnosis of sleep-related breath-
ing or movement disorder unlikely to explain her presentation.
Nor is she likely to have primary insomnia or hypersomnia disor-
der given her lack of symptoms on longer breaks from her school
when she is able to consistently delay her sleep schedule. Based
on her sleep logs, it is evident that the diagnosis that best fits
Hannah is DSWPD.
The International Classification of Sleep Disorders, Third
Edition (ICSD-3), lists DSWPD (formerly known as Delayed Sleep
Phase Syndrome) under the broad category of Circadian Rhythm
Sleep-Wake Disorders (CRSWD) [1]. In DSWPD, the problem lies
Fig. 2.1 Sample sleep logs. Sleep logs showing sleep-wake routines for
Hannah. Note the feeling of daytime tiredness on school days ceases during
winter break when a liberal sleep schedule is allowed
with an inability to initiate sleep at a socially acceptable time at

night. In affected individuals, the habitual sleep-wake timing is
usually delayed by more than 2 h as compared to the conventional
timing, even when an opportunity to sleep is available. This may
present very commonly as insomnia of sleep onset, given the
appearance of difficulty initiating sleep. Once asleep, an individual
with DSWPD usually does not experience difficulty maintaining
sleep. As a second component, the individual will report problems
waking up at an acceptable time the following day. Typically, this
results in delays getting out of bed and trouble coming to full func-
tional alertness upon awakening. This “sleep inertia” is common if
the affected individuals have to curtail their sleep to meet social
obligations such as going to school on time. However, a key fea-
ture of this disorder, assuming no other medical, psychiatric, or
sleep-related comorbidities, is that the sleep duration, quality, and
subsequent wakeful behavior and function is usually normal if the
person does not have any obligations to wake up at a certain time
the next day. Taken together, if left to select their own sleep and
rise times, the affected person prefers to go to bed and get up sig-
nificantly later than would be expected for the age and societal
norms and report no other sleep-related problems if allowed to
keep their favored schedules. Finally, since it is not uncommon for
similar changes in sleep-wake behaviors to occur from time to
time in normal individuals due to transient social or medical rea-
sons, a firm diagnosis requires that the problem be present for 3
months or longer and that it be substantiated by sleep logs or actig-
raphy typically spanning a period of a fortnight or more (Fig. 2.2).
DSWPD affects 7 to 16 % of adolescents and young adults [1].
Genetic factors such as polymorphisms in the circadian clock gene
hPer3, arylalkylamine N-acetyltransferase, human leukocyte anti-
gen, and Clock have been reported to be associated with DSWPD
[2–5]. Some familial aggregation has also been described [6].
Environmental, social, and behavioral factors also play an impor-
tant role in the development and perpetuation of this disorder.
DSWPD is a chronic disorder which may last into the middle and
geriatric ages although the prevalence appears to decrease with
increasing age [7, 8].
Fig. 2.2 Sample actigraphy chart. An actigraphy is a wrist watch-like device

with an embedded accelerometer which can graph rest-activity cycles as a
surrogate for sleep-wake. In the graphic, the clock hours are on the top
(00:00 denotes midnight) and days of the week are on the vertical axis. Dark
vertical lines in each row denote wrist activity implying wakefulness. This
data is from another patient seen by the authors who exhibited late bedtime
(red line) and rise times (blue line) except on 3 days when the teen did make
it to school on time!
Pitfalls
• DSWPD is a relatively common disorder that is frequently

missed in the primary care setting.
• DSWPD can be difficult to diagnose during the academic
school year given societal obligations to rise early.
Learning Points
• If excessive daytime sleepiness is a chief compliant, sleep logs

are a important diagnostic tool (actigraphy is useful if available).
• An adolescent with DSWPD will not experience difficulties
initiating sleep or excessive daytime sleepiness if allowed to
sleep and wake based on their personal circadian rhythm.
• Once asleep, adolescents with DSWPD generally do not expe-
rience difficulties maintaining sleep.
Case Presentation 2
Andrew is a laconic 15-year-old male who presents with his mother

for an initial sleep clinic visit with complaints of decreasing
academic performance, increased moodiness, behavioral concerns,
and an inability to initiate sleep. He denies symptoms of snoring,
restless legs, cataplexy, hypnagogic hallucinations, or sleep
paralysis.
Past psychiatric evaluation found a lack of motivation and
follow-through on recommended therapy. He was also prescribed
trazodone to assist with sleep initiation, but Andrew’s mother
states it has not been beneficial. His pediatrician also prescribed
methylphenidate on a hunch that he was experiencing EDS. This
drug caused him to lose weight and feel restless, and the medica-
tion was stopped.
When interviewed without his mother, Andrew admits feeling
tired in the morning and experiencing difficulty waking for school.
He also voices fear that his parents think he is “crazy” or on drugs.
Andrew confesses he felt awkward at the psychiatrist’s office
when he heard trazodone can cause his penis “to become painful”
and he chose to not take the medication. His mother is unaware of
this. He denies being sexually active, consuming alcohol or recre-
ational drugs. Andrew states he does drink some caffeine, usually
Mountain Dew, in the morning to help him concentrate at school
and clear his foggy brain. He does not doze in class but occasion-
ally naps on the bus.
When asked about his sleep habits during school breaks,
Andrew confesses that twice a year his family vacations in Hawaii
and that he feels fine. While in Hawaii, he is in bed by 10:00 pm,
he initiates sleep quickly, and is up before his family and ready to
hit the beach. He often teases his family who appear to be experi-
encing jetlag for the whole week they are on vacation.
His physical examination is unremarkable and a urine drug
screen is negative.
A diagnosis of DSWPD is made. The circadian rhythm is
explained to Andrew and his mother. Andrew’s interest in biology
and science, and validation that he is not “crazy” evoke a flurry of
questions. He is eager to try phase advancement with the help of
low-dose melatonin and morning exposure to sunlight. His mother

describes his sister’s bedroom as facing East, and it is agreed to
have him switch rooms with his sister to allow morning sunlight
exposure and use room-darkening shades at night.
Discussion
While several case reports have documented the effectiveness of

phase shifting, there have been no controlled trials in adolescents
[9]. Phase advancement is best used when a targeted sleep
onset time and the current sleep onset time are less than 3 h apart.
Bedtimes and wake-times are gradually moved earlier (by 15 to
30 min a day) until the targeted sleep and wake-times are reached.
The starting bedtime is set at a time that the adolescent is consis-
tently able to initiate sleep quickly. The pace (shifting times earlier
every 1 day, 2 days, 3 days) and time increments (shifting by 5
min, 15 min, 30 min) is case specific and dependent on patient
response to treatment and how quickly the shift in bedtime and
wake-times must be accomplished. The longer the delayed sleep
phase has been sustained, the more gradual the process might need
to be (Table 2.1).
Use of over-the-counter melatonin is also a treatment option in
DSWPD. Melatonin is a hormone secreted by the human pineal
Table 2.1 Sample phase advancement schedule

Bedtime Waketime
Current 12:00 AM 9:00 AM
Night 1 11:45 8:45
PM AM
Night 2 11:30 8:30 AM
PM
Night 3 11:15 8:15
PM AM
Night 4 11:00 8:00
PM AM
*Continue to advance both bed/wake times by 15 min each day to goal
Goal sleep period: 10:30 PM to 7:30 AM
a 3
Advance
2
Phase Shift (h)
1
-1
Delay
-2
-3
-9 -6 -3 0 3 6 9 12 15
Time Relative to Baseline DLMO (h)
14 17 20 23 2 5 8 11
Average Clock Time (h)
b
2
Phase Shift (h)
1
0
-1
-2
-3
-4
6 9 12 15 18 21 0 3 6 9 12 15 18
Circadian Phase
(Melatonin midpoint = 22 h)
Fig. 2.3 (a) Melatonin phase response curve. The three pulse phase response
curve (PRC) to 3 mg of exogenous melatonin generated from subjects free-
running during an ultradian LD cycle. Phase shifts of the DLMO are plotted
against the time of administration of the melatonin pill relative to the base-
line DLMO (top x-axis). The average baseline DLMO is represented by the
upward arrow, the average DLMOff by the downward arrow, and the aver-
age assigned baseline sleep times from before the laboratory sessions are
enclosed by the vertical lines. Each dot represents the phase shift of an indi-
vidual subject, calculated by subtracting the phase shift during the placebo
session (free-run) from the phase shift during the melatonin session. The
curved line illustrates the dual harmonic curve fit. The average clock
time axis (bottom x-axis) corresponds to the average baseline sleep times.
This PRC can be applied to people with different sleep schedules by mov-
ing the average clock time axis until the vertical lines align with the individu-
al’s sleep schedule. Figure and legend reprinted with permission from [12].
gland in a well-defined 24-h cycle. During the daytime, levels of

melatonin are nearly absent and will rise into the evening as one
nears their usual bedtime. During the nighttime, levels of melato-
nin remain relatively constant and will decline as one nears a typi-
cal waketime [10]. The American Academy of Sleep Medicine
(AASM) has recently released an updated clinical practice guide-
line for the treatment of intrinsic CRSWDs, which suggests that
there is some evidence to support the use of strategically timed
melatonin to treat DSWPD in children and adolescents [11].
Several studies have found physiologic doses of oral melatonin
(0.3–0.5 mg) administered in afternoon or early evening hours
(i.e., 5–7 h before typical sleep onset) seem to be most effective
in advancing the sleep phase [9]. However, inappropriately timed
melatonin could worsen a phase delay. Melatonin can also have
hypnotic effects when given in larger doses just before bedtime.
Unfortunately, at this time there is no consensus on the ideal time
to take melatonin to achieve a phase advance [9] but research sug-
gests a predictable physiological response [12] (Fig. 2.3a).
Another treatment modality for phase advancement that should
be considered is bright light therapy which shows a similar phase
response physiology [13] (Fig. 2.3b). By exposing an adolescent
to bright light at an appropriate time, the circadian rhythm may be
shifted earlier, allowing an adolescent to initiate sleep earlier.
However, much like melatonin dosages, there are no currently
established guidelines regarding intensity, duration, and time of
Fig. 2.3 (continued) (b) Light phase response curve The PRC to the bright
light stimulus using melatonin midpoints as the circadian phase marker. Phase
advances (positive values) and delays (negative values) are plotted against the
time of the center of the light exposure relative to the melatonin midpoint on
the pre-stimulus CR (defined to be 22 h), with the core body temperature mini-
mum assumed to occur 2 h later at 0 h. Data points from circadian phases 6–18
are double plotted. The filled circles represent data from salivary melatonin in
subject 1 8K8 from whom blood samples were not acquired. The solid curve
is a dual harmonic function fitted through all of the data points. The horizontal
dashed line represents the anticipated 0.54 h average delay drift of the pace-
maker between the pre- and post-stimulus phase assessments. Figure and
legend reprinted with permission from [13]
light exposure. It should be noted that light exposure at the wrong

time could exacerbate a phase delay. In simple cases and sunny
places, light exposure may be as easy as eating breakfast in a
sunny area or early morning sun exposure. In more complicated
cases or cloudy areas, regimented exposure for 20–30 min to
bright light (2500 to 10,000 lux) from specially designed light
boxes in the early morning (e.g., 6:00 to 8:00 am) may be benefi-
cial [9]. There are a number of commercially available bright light
therapy models that can be purchased online.
As with melatonin, knowledge of phase response to light ther-
apy is essential since wrongly timed light can worsen
DSWPD. Thus, bright light should also be avoided in the evening
or late in the day through the use of dark glasses or dimming of
lights. The concept behind strategic avoidance of light is based on
the known melatonin-suppressing effect of light. Exposure to light
in the evening and before the core body temperature minimum
(CBTmin) leads to phase delays [14]. The greater the intensity and
duration of light exposure, the greater the effects on the circadian
rhythm [15, 16]. Thus, a combination of melatonin and bright light
therapy is frequently used for phase advancement (Fig. 2.4).
An alternative treatment option to phase advancement is phase
delay (chronotherapy) which is typically used in more severe cases
of DSWPD, when the shift needed is greater than 3 h (Table 2.2).
Chronotherapy involves delaying bedtime and waketime by
2–3 h every 1–2 days based on the fact that for most people it is
often easier to go to bed and initiate sleep later than it is to initiate
sleep earlier, allowing for larger shifts to occur. Because shifts in
bedtime are larger during chronotherapy, the circadian rhythm can
be reset quickly. As a corollary, this is best done during school
breaks [17]. Research has found that chronotherapy is highly
effective particularly when used in conjunction with bright light
therapy [18, 19].
Pitfalls
• Often an erroneous diagnosis of insomnia or hypersomnia is

made and sedatives or stimulants are prescribed.
• Substance use must always be considered in the differential
diagnosis.
Endogenous Melatonin Level
Exogenous
Bright light
melatonin
Normal sleep time

Delayed sleep time
Clock time
Fig. 2.4 Phase advancement using melatonin and bright light therapy. Normal
sleep time is dependent on the circadian clock. In normal persons, endogenous
melatonin rises in the evening a little before natural sleep onset and falls to
low levels before natural awakening in phase with external time cues such as
sunlight (blue curve). In delayed sleep-wake phase disorder this rhythm is
shifted to a later clock time such that the person goes to sleep and rises later
relative to acceptable social norms (red curve). Therapy with low-dose exog-
enous melatonin early in the evening (blue arrow) and/or bright light in the
morning (red arrow) has been used to shift the circadian phase towards normal
(phase advancement)
Table 2.2 Sample phase delay schedule (chronotherapy)

Bedtime Waketime
Current 4:00 AM 12:00 PM
Day 1 7:00 3:00
AM PM
Day 2 10:00 6:00
AM PM
Day 3 1:00 9:00
PM PM
Day 4 4:00 12:00
PM AM
*Continue to delay both bed/wake times for 3 h nightly to goal
Goal sleep period: 10:00 PM to 6:00 AM
Learning Points
• Westward travel may be transiently favorable for patients with

DSWPD, but DSWPD would “catch up” after a few days.
• Melatonin and bright light therapy are often used in conjunc-
tion to help with phase advancement.
• High levels of motivation and consistency are necessary for
successful phase advancement, and a sleep psychologist may
be beneficial in increasing motivation for behavior change.
• Once a circadian rhythm has been shifted, the shift can be
maintained by the use of judiciously timed evening melatonin
and morning bright light therapy.
Case Presentation 3
Carmen is an 18-year-old female presenting to the sleep clinic

with her mother with complaints of difficulties initiating sleep.
Being an avid member of her high school marching band and
recently being voted drum major, Carmen must be at school by
6:30 am each day. She reports that she goes to bed each night at
10:00 pm, but is unable to fall asleep until around midnight or 1:00
am. Her mother states she has removed all electronics from
Carmen’s room and charges Carmen’s cell phone in her room each
night to ensure she is not texting friends at night. Carmen reports
frustration associated with being unable to sleep at night and feel-
ing tired in the morning. Although Carmen denies actually taking
naps, she states she feels like she could fall asleep at any point
during the day if she tried. When asked if she drinks caffeine,
Carmen laughs and states, “all day long.” She admits to one cup of
coffee while getting ready for school in the morning. Between
band and her next class, Carmen and her friends often hang out at
a local coffee shop where she drinks another cup of coffee. Carmen
also has an after school job at a movie theater, where she often
drinks an additional two or three cups of caffeine while working.
She gets home from work around 9:30 pm. She has a well-defined
bedtime routine and works to keep a consistent bedtime on week
days and weekends.
Despite being a borderline obese teenage girl, Carmen’s physi-

cal exam is unremarkable. Her mother denies concerns of snoring
or sleep-related breathing problems. She denies experiencing any
hypnagogic and hypnopompic hallucinations, or cataplexy. Her
periods are regular. Her urine drug screen is negative.
Discussion
Although Carmen presents with symptoms similar to DSWPD, the

first line of treatment to ascertain any underlying sleep concerns
would be to reduce or eliminate the use of caffeine. As the most
commonly used psychoactive substance, caffeine has important
effects on sleep, especially in children and adolescents [20–25].
Naturally found in coffee, tea, and cocoa, it is also a common
ingredient in various beverages routinely consumed by children.
High caffeine users are more likely to have insufficient sleep on
school nights and perceive that they have a sleep problem and
associated daytime consequences such as sleepiness [26]. This
leads to a circular problem in that daytime sleepiness itself may
trigger increased caffeine use, which can in turn lead to delayed
sleep onset. Similarly, children with DSWPD tend to use caffeine
as a stimulant to counter daytime sleepiness [27].
The consumption of caffeine by children and adolescents has
been increasing over the past few decades [28]. Compared to
adults, children use soft drinks (and more recently energy drinks)
as their primary source of caffeine [29, 30]. Caffeine consumption
in children has significant physiological effects on heart rate and
diastolic blood pressure in a dose-dependent manner [31]. It has
also been linked to anger in adolescents, increased incidence for
mood disorders and substance use [32–34]. With an elimination
half-life as long as 10 h, the effects of caffeine on the body can be
long lasting [35].
Recently, there has been some concern that children may not be
aware about the caffeine content in their drinks. Previous national
polls have asked whether the children consumed caffeinated bev-
erages such as tea, soda, coffee, and energy drinks, but they did not
ask about specific kinds or brands of beverages consumed by the
children [36, 37]. In a recent study, our group found that there is a
significant lack of knowledge about caffeine content of common

drinks among 7th and 8th graders, with nearly 29 % being unaware
that their favorite drink(s) contain(s) caffeine and more than 50 %
unable to correctly identify the drinks with the most caffeine [38].
Our study also explored whether these children were aware that
even light colored sodas contain caffeine. A significant percent of
the subjects were unaware that many of their preferred light col-
ored drinks contain caffeine. Given the adverse effects of caffeine
on sleep and the low level of awareness among children and ado-
lescents of soda caffeine content, an important opportunity exists
for the education of children and their parents to decrease the
potential adverse effects of excessive caffeine consumption on
sleep.
Pitfalls
• Caffeine use can mask sleep-specific concerns, either by caus-

ing delayed sleep onset or by being used as a stimulant during
the daytime.
• Motivated teens may report to school on time and the diagnosis
may be missed.
Learning Points
• Caffeine and other psychostimulants can result in delayed sleep

onset.
• Children may unwittingly consume caffeine due to lack of
knowledge.
Case Presentation 4
Zachary is a 10-year-old male presenting to the sleep clinic with

his mother for trouble initiating sleep. According to his mother,
Zachary is unable to initiate sleep before 2:00 am and has shown
an increase in behavioral concerns over the last few months. Due
to a recent change in financial status, the family is currently living
with her parents and occupying the unfinished basement. She

describes his “bedroom” as a small area separated by hung bed-
sheets from the area of his younger sibling and his parents. His
mother places Zachary in bed when his 2-year-old brother goes to
bed, around 8:30 pm, and she watches TV in her bed until early
morning. Zachary does not have a TV in his “room” but does
have his own tablet, which he admits to using at night. The house
is located next to a local trauma hospital, and his mother
describes the neighborhood as being noisy. His mother endorses
hearing Zachary snoring and possibly some witnessed apneas.
Polysomnography (PSG) is ordered and no significant sleep-
related breathing events are noted. Interestingly, Zachary exhibits
96 % sleep efficiency during the PSG. Surprisingly to his mother,
he slept from 10:45 pm and awoke at 6:30 am when the sleep tech-
nician ended the PSG. Further questioning reveals that Zachary’s
mother watches TV in her room until his father comes home
around 1:45 am. Zachary tells the provider he listens to the TV
from his mother’s room while playing on his tablet and waiting
anxiously for his father to come home safe from work.
Discussion
In Zachary’s case, sleep-related breathing disorders needed to first be

ruled out as a diagnostic consideration through a PSG which provided
very valuable incidental information into Zachary’s sleep problems.
He did not exhibit difficulties with sleep initiation or maintenance as
at home or even as would typically be sometimes expected from a
“first night effect” during PSG. In fact, he slept so well his mother
disagreed with the findings! After much maternal education, sleep
hygiene then became the target of intervention for Zachary to deter-
mine if this would improve his delayed sleep onset.
Pitfalls
• Poor sleep hygiene can mimic DSWPD.

• Intervention entry points may often be missed if the social his-
tory and bedroom environment is not assessed.
Learning Points
• Sleep hygiene interventions are a useful part of all sleep-related

interventions.
• Good sleep hygiene includes: (1) identifying and implementing
a well-defined sleep/wake schedule; (2) keeping a predictable
age-appropriate napping schedule for young children but dis-
couraging naps for older children and teens; (3) promoting
quiet and non-stimulating activities prior to bedtime, which
can include positive parental interactions and predictable orga-
nized routines associated with bedtime such as warm baths and
reading; (4) ensuring a comfortable sleeping environment that
is dark, quiet, and cool, and preferably in an independent bed;
(5) avoiding the use of electronics close to bedtime, reserving
the bed for only sleep and not engaging in other activities like
watching TV, socializing, web-surfing, gaming, or homework;
(6) avoiding large meals and vigorous physical activity (e.g.
basketball practice) 2–3 h before bedtime; (7) avoidance of
substances that are known to disrupt sleep. This can include
(if applicable) chemicals like nicotine and stimulants close to
bedtime; and (8) limiting or avoiding caffeine intake during
the day.
Conclusion
DSWPD involves a persistent and significant phase shift in sleep-

wake preference that often conflicts with societal obligations and
demands including school and work start times. In DSWPD, the
timing of sleep is problematic, not the quality or quantity of sleep.
If allowed to sleep on their preferred schedule, individuals would
not express any concerns related to sleep initiation or maintenance.
DSWPD can occur at any age, but is most commonly seen in ado-
lescents and young adults, perhaps in line with the natural circa-
dian rhythm shift that often accompanies puberty. It is important
for providers to be aware of the symptoms of DSWPD and appro-
priately differentiate it from insomnia, hypersomnia, and second-
ary symptoms associated with other sleep disorders including
sleep-related breathing disorders. A comprehensive sleep history

with sleep logs and actigraphy (if available) are useful for an
appropriate diagnosis of DSWPD. A number of treatment options
exist including phase shifting, melatonin, bright light therapy, and
improvement in sleep hygiene. Successful outcomes hinge on
patient and familial buy-in and motivation.
Disclosure None of the authors has any financial support or conflicts of inter-
est to disclose.
References
1. International classification of sleep disorders. 3rd ed. Darien, IL: American
Academy of Sleep Medicine, 2014.
2. Archer SN, Carpen JD, Gibson M, Lim GH, Johnston JD, Skene DJ, et al.
Polymorphism in the PER3 promoter associates with diurnal preference
and delayed sleep phase disorder. Sleep. 2010;33(5):695–701.
3. Hohjoh H, Takasu M, Shishikura K, Takahashi Y, Honda Y, Tokunaga
K. Significant association of the arylalkylamine N-acetyltransferase
(AA-NAT) gene with delayed sleep phase syndrome. Neurogenetics.
2003;4(3):151–3.
4. Hohjoh H, Takahashi Y, Hatta Y, Tanaka H, Akaza T, Tokunaga K, et al.
Possible association of human leucocyte antigen DR1 with delayed sleep
phase syndrome. Psychiatry Clin Neurosci. 1999;53(4):527–9.
5. Ebisawa T. Circadian rhythms in the CNS and peripheral clock disorders:
human sleep disorders and clock genes. J Pharmacol Sci.
2007;103(2):150–4.
6. Ancoli-Israel S, Schnierow B, Kelsoe J, Fink R. A pedigree of one family
with delayed sleep phase syndrome. Chronobiol Int. 2001;18(5):831–40.
7. Yazaki M, Shirakawa S, Okawa M, Takahashi K. Demography of sleep
disturbances associated with circadian rhythm disorders in Japan.
Psychiatry Clin Neurosci. 1999;53(2):267–8.
8. Paine SJ, Fink J, Gander PH, Warman GR. Identifying advanced and
delayed sleep phase disorders in the general population: a national survey
of New Zealand adults. Chronobiol Int. 2014;31(5):627–36.
9. Circadian rhythm sleep-wake disorders. In: Mindell JA, Owens JA, edi-
tors. A clinical guide to pediatric sleep diagnosis and management of sleep
problems. 3rd ed. Philadelphia: Wolters Kluwer; 2015. p. 189–199.
10. Crowley SJ, Acebo C, Carskadon MA. Sleep, circadian rhythms, and
delayed phase in adolescence. Sleep Med. 2007;8(6):602–12.
11. Auger RR, Burgess HJ, Emens JS, Deriy LV, Thomas SM, Sharkey
KM. Clinical practice guideline for the treatment of intrinsic circadian
rhythm sleep-wake disorders. J Clin Sleep Med. 2015;11(10):1199–236.
12. Burgess HJ, Revell VL, Eastman CI. A three pulse phase response curve
to three milligrams of melatonin in humans. J Physiol. 2008;586(2):
639–47.
13. Khalsa SB, Jewett ME, Cajochen C, Czeisler CA. A phase response curve
to single bright light pulses in human subjects. J Physiol. 2003;
549(3):945–52.
14. St Hilaire MA, Gooley JJ, Khalsa SB, Kronauer RE, Czeisler CA, Lockley
SW. Human phase response curve to a 1 h pulse of bright white light.
J Physiol. 2012;590(13):3035–45.
15. Zeitzer JM, Dijk DJ, Kronauer R, Brown E, Czeisler C. Sensitivity of the
human circadian pacemaker to nocturnal light: melatonin phase resetting
and suppression. J Physiol. 2000;526(3):695–702.
16. Chang AM, Santhi N, St Hilaire M, Gronfier C, Bradstreet DS, Duffy JF,
et al. Human responses to bright light of different durations. J Physiol.
2012;590(13):3102–12.
17. Meltzer LJ, Crabtree VM. Pediatric sleep problems: a clinician’s guide to
behavioral interventions. Washington, DC: American Psychological
Association; 2015.
18. Lack LC, Wright HR. Clinical management of delayed sleep phase disor-
der. Behav Sleep Med. 2007;5(1):57–76.
19. Weitzman ED, Czeizler CA, Coleman RM, Spielman AJ, Zimmerman JC,
Dement W, et al. Delayed sleep phase syndrome. A chronobiological dis-
order with sleep-onset insomnia. Arch Gen Psychiatry. 1981;38(7):
737–46.
20. Nehlig A. Are we dependent upon coffee and caffeine? A review on human
and animal data. Neurosci Biobehav Rev. 1999;23(4):563–76.
21. Kaplan GB, Greenblatt DJ, Ehrenberg BL, Goddard JE, Cotreau MM,
Harmatz JS, et al. Dose-dependent pharmacokinetics and psychomotor
effects of caffeine in humans. J Clin Pharmacol. 1997;37(8):693–703.
22. Gilbert RM. Caffeine consumption. Prog Clin Biol Res. 1984;158:
185–213.
23. Mandel HG. Update on caffeine consumption, disposition and action.
Food Chem Toxicol. 2002;40(9):1231–4.
24. Orbeta RL, Overpeck MD, Ramcharran D, Kogan MD, Ledsky R. High
caffeine intake in adolescents: associations with difficulty sleeping and
feeling tired in the morning. J Adolesc Health. 2006;38(4):451–3.
25. Hughes JR, Hale KL. Behavioral effects of caffeine and other methylxan-
thines on children. Exp Clin Psychopharmacol. 1998;6(1):87–95.
26. Carskadon MA. Patterns of sleep and sleepiness in adolescents.
Pediatrician. 1990;17(1):5–12.
27. Lovato N, Gradisar M, Short M, Dohnt H, Micic G. Delayed sleep phase
disorder in an Australian school-based sample of adolescents. J Clin Sleep
Med. 2013;9(9):939–44.
28. French SA, Lin BH, Guthrie JF. National trends in soft drink consumption
among children and adolescents age 6 to 17 years: prevalence, amounts,
and sources, 1977/1978 to 1994/1998. J Am Diet Assoc. 2003;
103(10):1326–31.
29. Frary CD, Johnson RK, Wang MQ. Food sources and intakes of caffeine
in the diets of persons in the United States. J Am Diet Assoc.
2005;105(1):110–3.
30. Costa BM, Hayley A, Miller P. Young adolescents' perceptions, patterns,
and contexts of energy drink use. A focus group study. Appetite.
2014;80:183–9.
31. Temple JL, Dewey AM, Briatico LN. Effects of acute caffeine administra-
tion on adolescents. Exp Clin Psychopharmacol. 2010;18(6):510–20.
32. Warzak WJ, Evans S, Floress MT, Gross AC, Stoolman S. Caffeine con-
sumption in young children. J Pediatr. 2011;158(3):508–9.
33. Kristjansson AL, Sigfusdottir ID, Frost SS, James JE. Adolescent caffeine
consumption and self-reported violence and conduct disorder. J Youth
Adolesc. 2013;42(7):1053–62.
34. Samaranayake CB, Arroll B, Fernando AT. Sleep disorders, depression,
anxiety and satisfaction with life among young adults: a survey of univer-
sity students in Auckland, New Zealand. N Z Med J. 2014;127(1399):
13–22.
35. Magkos F, Kavouras SA. Caffeine use in sports, pharmacokinetics in man,
and cellular mechanisms of action. Crit Rev Food Sci Nutr. 2005;
45(7–8):535–62.
36. National Sleep Foundation. 2006 Sleep in America poll—teens and sleep.
https://sleepfoundation.org/sites/default/files/2006_summary_of_find-
ings.pdf. Accessed 21 Feb 2016.
37. National Sleep Foundation. 2011 Sleep in America poll. https://teensneed-
sleep.files.wordpress.com/2011/05/national-sleep-foundation-2011-sleep-
in-america-poll-communications-technology-in-the-bedroom.pdf .
Accessed 21 Feb 2016.
38. Thakre TP, Deoras K, Griffin C, Vemana A, Podmore P, Krishna J. Caffeine
awareness in children: insights from a pilot study. J Clin Sleep Med.
2015;11(7):741–6.
Restless Legs Syndrome
3
Mandana Mahmoudi and Sanjeev V. Kothare
Abbreviations
CKD Chronic Kidney Disease

FDA Food and Drug Administration
RLS Restless Legs Syndrome
SSRI Serotonin-Specific Reuptake Inhibitor
Case 1
Stephanie is a 14-year-old young woman who presents to clinic

with her parents due to concerns that she has been increasingly irri-
table during the daytime, and her school performance has been
declining over the past year. Her parents report that Stephanie has
been complaining of leg pains since the age of 9. They saw different
specialists in this regard, and she was told to have “growing pains.”
M. Mahmoudi, M.D.
Pulmonary, Critical Care, and Sleep Medicine, New York University
Langone Medical Center, New York, NY, USA
e-mail: mandana.mahmoudi@nyumc.org
S.V. Kothare, M.D. (*)
Department of Neurology, NYU Langone Medical Center
and NYU School of Medicine, 223 East 34th Street,
New York, NY, USA
e-mail: sanjeev.kothare@nyumc.org

28 M. Mahmoudi and S.V. Kothare
Stephanie states that she has trouble falling asleep at night, as her
legs ache and occasionally cramp when lying in bed. She some-
times gets up and walks around, but that relieves her leg discomfort
only temporarily. Her parents describe her sleep as “restless,” and
she “tosses and turns” at least for an hour until she falls asleep.
Until 1 year ago, she would not awaken during the night, but now
she awakens 3–4 times at night, unless exhausted. Her symptoms
are worse when she is very tired, and occur at least 2–3 times a
week. The only other change is that she started menstruating about
18 months ago, at age 13. She has a normal developmental history,
as well as a normal general and neurologic examination. Her family
history is notable for RLS in her maternal aunt and cousin.
Biochemical investigations reveal a normal thyroid function, vita-
min B12 and folic acid levels, transferrin saturation, and complete
blood count. Her serum ferritin level was 22 ng/ml. Polysomnography
revealed delayed sleep onset due to leg movements, as well as 8
PLMS per hour of sleep, most of which occurred in stage 2 sleep,
with 72% being associated with arousals from sleep. RLS was con-
firmed, likely in the setting of relative iron deficiency, and Stephanie
was started on a trial of oral iron combined with vitamin C to
enhance absorption. At 3-month follow-up, her ferritin level was
97 ng/ml, and her symptoms of leg discomfort, restlessness, and
daytime irritability resolved almost entirely.
Discussion
Stephanie was likely misdiagnosed with growing pains during

childhood. Her symptoms and polysomnographic findings are con-
sistent with RLS, and have likely been worsening over the past year
due to relative iron deficiency in the setting of growth, blood loss
with menses, and an underlying genetic predisposition for RLS.
RLS in adolescents is a common yet frequently undiagnosed neu-
rologic sensorimotor disorder, affecting approximately 2 % of male
and female adolescents, with at least one-third of adolescents
reporting moderate-to-severe symptoms [1]. The clinical course of
early-onset RLS has been described as slowly progressive in about
two-thirds of cases, which is consistent with a gradual increase in
prevalence with age. Even though its prevalence is higher than
non-febrile seizure disorders and diabetes type 1 and 2 in the same
3 Restless Legs Syndrome 29
age range, RLS remains frequently unrecognized, misdiagnosed,

and poorly managed [2–4].
The differential diagnosis of RLS should be entertained in ado-
lescents who have nighttime leg discomfort that cannot be attrib-
uted to vascular, bone, joint, tendon, or muscle disease. Symptoms
vary in severity, with some adolescents experiencing mild, infre-
quent symptoms and others having severe, daily symptoms.
Moderate-to-severe RLS in adolescents can influence their sleep,
daily activities, mood, and vitality [5–9]. RLS in adolescence can
present in a manner similar to that in adulthood with leg paresthe-
sias, motor restlessness, and symptoms at night and at rest with
partial relief by activity. Sleep-onset is frequently delayed due to
leg discomfort and is commonly associated with bedtime behav-
ioral problems. Restlessness during sleep in form of leg and arm
kicking as well as excessive rolling around contributes to sleep
disruption, often resulting in daytime sleepiness, behavioral prob-
lems, and decline in academic functioning [10].
The pathophysiology of RLS remains poorly understood; yet, the
clinical manifestations of RLS are likely mediated by genetic and
environmental influences, including central nervous system dopa-
mine dysfunction and brain iron deficiency [11–15]. RLS can occur
as a primary disorder with no apparent cause other than perhaps a
genetic predisposition. It can also occur as a secondary condition,
often in the setting of iron deficiency, pregnancy, chronic renal failure
or chronic neurologic disorders and is exacerbated by some medica-
tions [16–22]. Patients with early-onset RLS are more likely to have
affected family members, while those with late-onset RLS are more
likely to have secondary etiologies. In the diagnostic process, it is
important to appreciate that any of these etiologies can co-occur [23].
Stephanie’s case is a classic presentation of RLS in the setting of
relative iron deficiency. A strong relation between body iron stores
and the severity of RLS symptoms has been shown, and iron ther-
apy even without the presence of anemia improves RLS symptoms
[24–26]. Goal should be to achieve an optimal iron status, rather
than the usually defined “normal” range. Treatment with oral iron
in adolescents is therefore recommended with a serum ferritin level
below 50 ng/ml [10, 27]. A serum ferritin concentration between 50
and 100 ng/ml is recommended, which generally reflects adequate
body iron stores, unless this value is falsely elevated by an inflam-
matory state. Iron supplements should be taken with vitamin C to
enhance iron absorption. Iron studies should be done every 3 months

to check on treatment progress. Once iron stores have been restored,
serum ferritin levels should be monitored periodically. In adoles-
cents, it may be difficult to reach and maintain a serum ferritin level
above 50 ng/ml due to growth. This particularly affects adolescent
girls due to blood loss with menses. It is important to monitor ado-
lescents during treatment with therapeutic doses of iron to avoid the
rare but serious complication of iron overload, which can occur in
individuals who carry hemochromatosis genes [28].
Pitfalls
• A strong relation between body iron stores and the severity of

the RLS symptoms has been shown, and iron therapy even
without the presence of anemia improves RLS symptoms.
• In the treatment of RLS, the goal should be to achieve an opti-
mal iron status, rather than the usually defined “normal” range.
Learning Points
• Treatment with oral iron is recommended with serum ferritin

levels below 50 ng/ml.
• The target serum ferritin concentration lies between 50 and
100 ng/ml, which generally reflects adequate body iron stores,
unless this value is falsely elevated by an inflammatory state.
Case 2
Mark is a 17 year-old young man who initially presented to the

office 9 months ago due to parental concerns regarding depressed
mood, irritability, emotional instability, and difficulty concentrat-
ing. He underwent a comprehensive medical and psychiatric
evaluation and was diagnosed with major depressive disorder.
His symptoms improved gradually after initiation of fluoxetine
20 mg daily. He returned again accompanied by his mother with
the concern for worsening depression. His teachers noted increased
daytime sleepiness and inattentiveness, resulting in worsening
school performance. Mark states that he goes to bed around 10 pm,

however, for the past couple of months he has difficulty falling
asleep for up to 2 h due to an itching sensation in his legs at night.
He rubs his legs against bedclothes, reducing his leg discomfort
partially. He does not experience leg discomfort during the day-
time. In the mornings, he does not feel rested and struggles not to
fall asleep in class. He does not have a past medical history or fam-
ily history of psychiatric or neurological illnesses. He denies
tobacco use, alcohol, or caffeine intake. His detailed general and
neurological physical examination, as well as biochemical investi-
gations, including ferritin and folic acid levels, resulted normal.
He does not take any medications besides fluoxetine. In view of his
above symptoms and investigations, RLS related to fluoxetine was
considered to be the probable cause. The decision was made to
taper off fluoxetine and to introduce bupropion instead. Four days
later, his symptoms of RLS started to diminish and, after 3 weeks,
his clinical symptoms disappeared entirely. On 6-months follow-
up, the patient did not manifest clinically significant RLS.
Discussion
The diagnosis of RLS is based on the presence of clinical diagnos-

tic criteria. Mark’s presentation meets the essential criteria for the
diagnosis of RLS, namely (a) desire to move the limbs, often asso-
ciated with paresthesia or dysesthesia; (b) symptoms are present or
worsen only during rest and are partially or temporarily relieved
with activity; (c) motor restlessness; and (d) nocturnal worsening
of symptoms [29].
Physicians have to rely to a great extent on patients’ descriptions
of timing, frequency and severity of symptoms, as well as informa-
tion from their medical history, family history, social history, and
current medications. While language development can be a limit-
ing factor in the assessment of children, adolescents are generally
able to provide relevant information on their symptoms and history
to distinguish RLS from other etiologies [4]. Common RLS mim-
ics in adolescents include positional discomfort, nocturnal cramps,
nocturnal myoclonus, volitional movements, foot tapping, leg
rocking, or arthritis. Various other conditions can appear like RLS
though many of those mostly affect adults (Table 3.1) [30, 31].
Table 3.1 Common Mimics of RLS [31, 62]
32
Urge to Sensory Sleep Circadian

Disorder Description Move Symptoms Disruption Pattern
Sleep-related disorders
• Periodic limb Involuntary leg movements while asleep, at regular intervals No No Maybe Yes
movements before one enters REM sleep. People who suffer from PLMS
of sleep can be unaware of their limb movements, as they do not always
wake from them. Sleep disturbance and daytime sleepiness
may be present. Diagnosis made by polysomnography. Positive
response to dopaminergic therapy
• Nocturnal Involuntary myoclonic twitch occurring once or twice while No No No Yes
myoclonus falling asleep. May cause sudden awakening for a moment
Neurological disorders
• Neuroleptic-induced Appears like severe RLS but affects the entire body, often seen Yes Yes Yes Yes
akathisia as entire body rocking. Less circadian pattern and less relief
from movement. Associated with dopamine antagonists
• Hypotensive Feeling of restlessness, brought on by sitting still, which may Yes No No No
akathisia be localized in legs; should not occur while lying down but
might be relieved by movement; occurs in patients with
orthostatic hypotension
• Volitional Occurs in subjects who fidget, especially when bored or Yes No No No
movements, foot anxious, but usually not associated with sensory symptoms,
tapping, leg rocking discomfort, or conscious urge to move. Symptoms do not
bother the subject, usually lack a circadian pattern, and do not
M. Mahmoudi and S.V. Kothare
cause sleep disturbances

Disorder Description Move Symptoms Disruption Pattern 3
• Painful legs and Predominant involvement of feet. Movement is truly Yes No No No
moving toes involuntary, no circadian pattern. Usually a continuous slow
writhing
• Isolated leg Fast (>3 Hz) rhythmic plantar flexion/dorsiflexion movements Yes No No No
stereotype oscillating around ankle, but sometimes involving other parts
of the leg. Usually a tremor phenotype, but not considered a
true tremor. It is easily suppressed and is almost always seen
only while sitting. The condition is common, not considered
pathologic, and may be an alerting activity
Restless Legs Syndrome
• Orthostatic tremor Fine leg tremor manifest by a sense of poor balance while Yes No No No
standing, but not while walking. Therefore, patients cannot
stand still but need to walk. Unlike RLS, there are no symptoms
while sitting or lying down and no circadian pattern
• Nocturnal cramps Leg cramps that come on at night and are relieved with No No No Yes
stretching or walking. Experienced as an unusually painful
muscular contraction, often involving the calf muscles. Unlike
RLS, sensations are sudden onset, short duration, usually
palpable contractions
• Arthritis, lower Discomfort centered mostly in joints, increased with movement No No No No
limb pain
• Positional Often comes on with prolonged sitting or lying in the same No No No No
discomfort position, but usually relieved by a simple change in position
(continued)
33
Table 3.1 (continued)
34

Disorder Description Move Symptoms Disruption Pattern
Vascular disorders
• Vascular Muscle pain often in form of ache, cramp, numbness or sense No Maybe No No
claudication of fatigue, classically in the calf muscle, which occurs during
exercise, such as walking, and is relieved by rest, often best in
a lying position
• Varicose veins May have discomfort in legs, some relief with massage or No No No No
inactivity
Pain disorders
• Myelopathy, Sensory symptoms and pain in the legs, frequently one-sided, No Yes Maybe No
radiculopathy often radicular, with atrophic changes of musculature
• Peripheral Sensory symptoms often in form of numbness, burning, and No Yes Maybe No
neuropathy pain. Complete and persistent relief is not obtained during
sustained movement
• Isolated leg pain Undiagnosed leg pain or ache in the muscle may be seen No No Maybe No
without other explanation. The examination and evaluation is
normal. Often worse at night and may improve with movement
but there is no true urge to move
• Fibromyalgia Multiple, alternating, varied complaints in muscle groups and No No Yes No
joints; sometimes leg accentuated but mostly whole body
affected. Frequent sleep disturbances, but no circadian pattern,
no relief from movement
M. Mahmoudi and S.V. Kothare
RLS may be a primary or a secondary condition. Secondary

RLS is thought to be due to an underlying medical condition or in
association with the use of certain drugs. The strongest evidence
for drug-induced RLS has been shown in fluoxetine, escitalopram,
levodopa, carbidopa, pergolide, levothyroxine, mianserin, mir-
tazapine, olanzapine, and tramadol [32]. Involvement of the dopa-
minergic system in RLS is supported by the great response of RLS
to dopamine agonists [33]. Antidepressants, particularly sero-
tonin-specific reuptake inhibitors (SSRI), such as fluoxetine inhibit
the dopamine system and can evoke dopamine-dependent side
effects and exacerbate RLS [34, 35]. In Mark’s case, RLS was
induced by fluoxetine and resolved with removal of the agent. The
antidepressant bupropion was particularly beneficial in this case,
as it also inhibits dopamine reuptake and has shown to be effective
in RLS without dopamine-like side effects, such as rebound or
tolerance [36, 37].
RLS can influence sleep and daytime functioning. It is therefore
important to avoid drugs that may provoke RLS although potential
offending medications such as antidepressants should be withdrawn
only after considering the patient’s overall status and in consulta-
tion with other health providers.
Pitfalls
• RLS is frequently overlooked as a side effect of certain

medications.
• Common mimics in adolescents are positional discomfort, noc-
turnal cramps, nocturnal myoclonus, volitional movements,
foot tapping, leg rocking, or arthritis.
Learning Points
• Knowledge of medication side effects and interactions is criti-

cal to physicians and their patients.
• Evaluation for possible medication side effects is important on
every patient encounter.
Case 3
Christopher is a 15-year-old young man who was diagnosed with

stage II chronic kidney disease (CKD) in the setting of reflux
nephropathy 2 years ago. He presents to the office with his parents
with the complaints of difficulty sleeping and fatigue, and the con-
cern that his renal function may be causing his symptoms. In the
course of the conversation, he discloses leg pain and a tingling sen-
sation in the evenings when lying in bed. His symptoms improve
temporarily with movement. Following further inquiry, Christopher
realizes that he has been having these symptoms for at least 1 year,
but they have been increasingly bothersome for the past couple of
weeks. He denies tobacco use, alcohol, or caffeine intake. He takes
nephro vitamins on a daily basis. His detailed general and neuro-
logical physical examination has been normal. Results of his bio-
chemical investigations showed further decline in his renal function
to stage III CKD, but normal complete blood count, serum ferritin,
transferrin saturation, thyroid function, vitamin B12, and folic acid
levels. His clinical picture raised concern for RLS related to
CKD. As agreed with Christopher and his parents, the decision was
made to initiate a treatment trial with Gabapentin 100 mg at bed-
time. On 2-weeks follow-up, Christopher reports notably reduced
leg pain and tingling, as well as improved sleep and daytime energy.
Discussion
Sleep disorders are common in adolescents with CKD and fre-

quently occur even before the need for renal replacement therapy.
RLS is one of the most common sleep disorders in patients with
CKD and has been reported to affect up to one-third of adolescents
[38, 39]. The severity of CKD correlates with the severity of RLS
symptoms: mild renal dysfunction has minimum or no impact on
the development of RLS, while those with end-stage renal disease
experience the most severe symptoms [40–42].
The exact etiology of RLS in patients with CKD is unknown.
The importance of uremia as a cause of RLS has been shown on the
one hand through improved symptoms in dialysis patients after suc-
cessful renal transplantation, and on the other hand, by recurrence
of symptoms in those with progressive renal dysfunction [43].

Additional risk factors include iron deficiency, anemia, periph-
eral neuropathy associated with uremia, and alterations in dopami-
nergic and opioid neuronal pathways within the central nervous
system [44].
Non-pharmacologic therapies are the initial step in the treatment
of RLS in adolescents. These focus on correction of contributing fac-
tors, such as appropriate bedtime habits, use of local comfort aids for
leg discomfort, intake of a healthy and well-balanced diet, avoidance
of caffeinated products, elimination of unnecessary medications,
moderate regular exercise, including over the counter products and
herbal products [45–49].
The decision to initiate pharmacologic therapy should be indi-
vidualized, with the goals of therapy to reduce RLS symptoms,
sleep disturbance, functional limitations, and to improve quality of
life. Pharmacological therapies are usually reserved for cases of
moderate to severe RLS with significant functional limitations and
should be combined with non-pharmacological measures to achieve
optimal results. Even though there are no FDA approved medica-
tions for the treatment of RLS in adolescents, the medical literature
supports the careful use of certain medications [50–53]. Treatment
should be initiated at the lowest dose possible, with slow symptom-
based up-titration, while monitoring for adverse effects [31].
The first step usually consists of micronutrient supplementa-
tion, in particular iron and folic acid [54, 55]; however, ferritin
levels are generally higher in individuals with impaired renal func-
tion due to their chronic inflammatory state [56]. It is therefore
difficult to show a relation between ferritin levels and the presence
of RLS in the CKD population, even though two-thirds of these
patients have been shown to be iron deficient [39]. Even though
Christopher’s ferritin levels were normal, iron therapy may have a
beneficial effect, as clinical experience has shown response to iron
replacement therapy in individuals with RLS in the setting of CKD.
Other pharmacologic agents that can be considered in the treat-
ment of RLS include dopaminergic agents (e.g., carbidopa-
levodopa), dopamine agonists (e.g., ropinirole, pramipexole),
benzodiazepines (e.g., clonazepam), anticonvulsants (e.g., gaba-
pentin), and others including clonidine [57–60]. Special attention
is recommended when initiating pharmacologic therapies in
adolescents with renal dysfunction. For example, Gabapentin’s

renal excretion is proportional to the individual’s renal function;
dose adjustment is recommended based on creatinine clearance,
and supplemental dosing is needed after hemodialysis. Pramipexole
is also cleared predominantly via renal excretion; utmost caution is
recommended when used in individuals with renal impairment,
and dose adjustment may be necessary. In contrast, ropinirole is
extensively metabolized through the liver; dose adjustments are
not required for individuals with CKD, neither are post-dialysis
supplemental doses needed [33, 61–65]. Some of these agents will
be removed with dialysis, which may result in worsening of RLS
symptoms and will require post-dialysis supplemental dosing
(Table 3.2).
It is important to routinely monitor adolescents with CKD for
potential sleep problems, as the presence of a sleep disorder con-
tributes to morbidity in the adolescent population, such as depres-
sion, behavioral problems, inattention, poor school performance,
and reduced quality of life [66–69]. Referral to a sleep specialist
should be considered if sleep problems arise, since early recogni-
tion and adequate treatment of sleep disturbances will likely have a
positive impact on the development of adolescents with CKD [70].
Pitfalls
• Sleep disorders are common in adolescents with CKD and fre-

quently occur even before the need for renal replacement
therapy.
• RLS is one of the most common sleep disorders in patients with
CKD and has been reported to affect up to one-third of
adolescents.
Learning Points
• The presence of a sleep disorder is an important contributing

factor to morbidity in the general adolescent population, as it
has been associated with depression, behavioral problems, inat-
tention, poor school performance, and reduced quality of life.
Table 3.2 Commonly used medications for treatment of RLS [31, 33, 62, 63]
Post-dialysis
Mechanism Dose Adjustment supplemental
Drug of action Dosage Metabolism Excretion in CKD Dialyzable dosing Adverse effects
Clonidine Central α2 0.05–0.3 mg Extensively hepatic to Urine (40–60 % as Yes No No Hypotension,
adrenergic inactive metabolites; unchanged drug) bradycardia, dry mouth
receptor agonist enterohepatic
recirculation
Clonazepam GABA-A 0.01 mg/kg Extensively hepatic Urine (<2 % as No (cautious use in No No Daytime sedation,
receptor agonist via glucuronide and unchanged drug); CKD, metabolites cognitive difficulties,
sulfate conjugation excreted metabolites may accumulate) antegrade amnesia
Levodopa/ Metabolic 25/100 mg Peripheral tissue and Urine No (contraindicated No No Hallucinations,
Carbidopa precursor of (up to 3 tabs/ CNS in uncompensated confusion, orthostatic
dopamine day) renal disease) hypotension
Pramipexole Nonergot 0.125– Negligible (<10 %) Urine (90 % as No (cautious use) No No Headaches,
dopamine 0.75 mg unchanged drug) hypotension,
receptor agonist insomnia, daytime
somnolence
Ropinirole Nonergot 0.5–4 mg Extensively hepatic Urine (<10 % as No No No Headaches,
dopamine via CYP1A2 to unchanged drug, hypotension,
receptor agonist inactive metabolites 60 % as metabolites) insomnia, daytime
somnolence
Gabapentin May potentiate 100–500 mg Not metabolized Urine (as unchanged Yes Yes Yes Drowsiness,
neuronal GABA drug); proportional irritability, worsening
synthesis to renal function behaviors
• Routine monitoring of adolescents with CKD for potential

sleep problems is recommended, with referral to a sleep spe-
cialist if problems arise, since early recognition and adequate
treatment of sleep disturbances will hopefully have a positive
impact on the development of adolescents with CKD.
Disclosure None of the authors have any financial support or conflicts of

interest to disclose.
No off label use of drugs or products have been discussed in the
manuscript.
References
1. Piccietti D, Allen RP, Walters AS, Davidson JE, Myers A, Ferini-Strambi
L. Restless legs syndrome: prevalence and impact in children and adoles-
cents—the Perds REST study. Pediatrics. 2007;120(2):253–66.
2. Winkelmann J, Wetter TC, Collado-Seidel V, Gasser T, Dichgans M,
Yassouridis A, Trenkwalder C. Clinical characteristics and frequency of
the hereditary restless legs syndrome in a population of 300 patients.
Sleep. 2000;23(5):597–602.
3. Allen RP, Walters AS, Monteplaisir J, Hening W, Myers A, Bell TJ,
Ferini-Strambi L. Restless legs syndrome prevalence and impact: REST
general population study. Arch Intern Med. 2005;165(11):1286–92.
4. Picchietti DL, Stevens HE. Early manifestations of restless legs syndrome
in childhood and adolescence. Sleep Med. 2008;9(7):770–81.
5. Abetz L, Allen R, Follet A, Washburn T, Earley C, Kirsch J, Knight H.
Evaluating the quality of life of patients with restless legs syndrome. Clin
Ther. 2004;26(6):925–35.
6. Abetz L, Allen R, Washburn T, Early C. The impact of restless legs syndrome
(RLS) on sleep and cognitive function. Eur J Neurol. 2004;9 Suppl 2:50.
7. Hornyak M, Kopasz M, Berger M, Riemann D, Voderholzer U. Impact of
sleep- related complaints on depressive symptoms in patients with restless
legs syndrome. J Clin Psychiatry. 2005;66(9):1139–45.
8. Hornyak M, Feige B, Voderholzer U, Philipsen A, Riemann D. Polysom-
nography findings in patients with restless legs syndrome and in healthy
controls: a comparative observational study. Sleep. 2007;30(7):861–5.
9. Walters AS, Silvestri R, Zucconi M, Chandrashekariah R, Konofal
E. Review of the possible relationship and hypothetical links between
attention deficit hyperactivity disorder (ADHD) and the simple sleep
related movement disorders, parasomnias, hypersomnias, and circadian
rhythm disorders. J Clin Sleep Med. 2008;4(6):591–600.
10. Garcia-Borreguero D, Stillman P, Benes H, Buschmann H, Chaudhuri KR,
Gonzalez Rodríguez VM, Högl B, Kohnen R, Monti GC, Stiasny-Kolster
K, Trenkwalder C, Williams AM, Zucconi M. Algorithms for the diagnosis
and treatment of restless legs syndrome in primary care. BMC Neurol.

2011;11:28.
11. Beard JL, Connor JR. Iron stores and neural functioning. Annu Rev Nutr.
2003;23:41–58.
12. Allen R. Dopamine and iron in the pathophysiology of restless legs syn-
drome (RLS). Sleep Med. 2004;5(4):385–91.
13. Winkelmann J, Polo O, Provini F, Nevsimalova S, Kemlink D, Sonka K, Högl
B, Poewe W, Stiasny-Kolster K, Oertel W, de Weerd A, Strambi LF, Zucconi
M, Pramstaller PP, Arnulf I, Trenkwalder C, Klein C, Hadjigeorgiou GM,
Happe S, Rye D, Montagna P. Genetics of restless legs syndrome (RLS): state-
of-the-art and future directions. Mov Disord. 2007;22 Suppl 18:S449–58.
14. Walters AS, Ondo WG, Zhu W, Le W. Does the endogenous opiate system
play a role in the restless legs syndrome? A pilot post-mortem study.
J Neurol Sci. 2009;279(1–2):62–5.
15. Picchietti MA, Picchietti DL. Advances in pediatric restless legs syndrome:
iron, genetics, diagnosis and treatment. Sleep Med. 2010;11:643–51.
16. Winkelman JW, Chertow GM, Lazarus JM. Restless legs syndrome in
end-stage renal disease. Am J Kidney Dis. 1996;28:372–8.
17. Rutkove SB, Matheson JK, Logigian EL. Restless legs syndrome in
patients with polyneuropathy. Muscle Nerve. 1996;19:670–2.
18. Sun ER, Chen CA, Ho G, Earley CJ, Allen RP. Iron and the restless legs
syndrome. Sleep. 1998;21:371–7.
19. Kavanagh D, Siddiqui S, Geddes CC. Restless legs syndrome in patients
on dialysis. Am J Kidney Dis. 2004;43:763–71.
20. Manconi M, Govoni V, De Vito A, Economou NT, Cesnik E, Casetta I,
Mollica G, Ferini-Strambi L, Granieri E. Restless legs syndrome and preg-
nancy. Neurology. 2004;63(6):1065–9.
21. Gemignani F, Brindani F, Negrotti A, Vitetta F, Alfieri S, Marbini A. Restless
legs syndrome and polyneuropathy. Mov Disord. 2006;21:1254–7.
22. Gemignani F, Brindani F, Vitetta F, Marbini A, Calzetti S. Restless legs
syndrome in diabetic neuropathy: a frequent manifestation of small fiber
neuropathy. J Peripher Nerv Syst. 2007;12:50–3.
23. Hening WA, Allen RP, Washburn M, Lesage SR, Earley CJ. The four diag-
nostic criteria for restless legs syndrome are unable to exclude confound-
ing conditions (“mimics”). Sleep Med. 2009;10(9):976–81.
24. Connor JR, Boyer PJ, Menzies SL, Dellinger B, Allen RP, Ondo WG,
Earley CJ. Neuropathological examination suggests impaired brain iron
acquisition in restless legs syndrome. Neurology. 2003;61(3):304–9.
25. Earley CJ, Barker PB, Horska A, Allen RP. MRI-determined regional
brain iron concentrations in early-and late-onset restless legs syndrome.
Sleep Med. 2006;7(5):458–61.
26. Godau J, Klose U, Di Santo A, Schweitzer K, Berg D. Multiregional brain
iron deficiency in restless legs syndrome. Mov Disord. 2008;23(8):1184–7.
27. Wang J, O’Reilly B, Venkataraman R, Mysliwiec V, Mysliwiec A. Efficacy
of oral iron in patients with restless legs syndrome and a low-normal fer-
ritin: a randomized, double-blind, placebo-controlled study. Sleep Med.
2009;10(9):973–5.
28. Barton JC, Wooten VD, Acton RT. Hemochromatosis and iron therapy of
restless legs syndrome. Sleep Med. 2001;2(3):249–51.
29. Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS,
Winkelman JW, Zucconi M, Ferri R, Trenkwalder C, Lee HB, International
Restless Legs Syndrome Study Group. Restless legs syndrome/Willis-
Ekbom disease diagnostic criteria: updated International Restless Legs
Syndrome Study Group (IRLSSG) consensus criteria—history, rationale,
description, and significance. Sleep Med. 2014;15(8):860–73.
30. Chervin RD, Archbold KH, Dillon JE, Pituch KJ, Panahi P, Dahl RE,
Guilleminault C. Associations between symptoms of inattention, hyperac-
tivity, restless legs, and periodic leg movements. Sleep. 2002;25:213–8.
31. Khatwa U, Kothare SV. Restless legs syndrome and periodic limb movements
disorder in the pediatric population. Curr Opin Pulm Med. 2010;16(6):559–67.
32. Hoque R, Chesson Jr AL. Pharmacologically induced/exacerbated restless
legs syndrome, periodic limb movements of sleep, and REM behavior dis-
order/REM sleep without atonia: literature review, qualitative scoring, and
comparative analysis. J Clin Sleep Med. 2010;6(1):79–83.
33. Garcia-Borreguero D, Kohnen R, Silber MH, Winkelman JW, Earley CJ,
Högl B, Manconi M, Montplaisir J, Inoue Y, Allen RP. The long-term
treatment of restless legs syndrome/Willis-Ekbom disease: evidence-
based guidelines and clinical consensus best practice guidance: a report
from the International Restless Legs Syndrome Study Group. Sleep Med.
2013;14:675–84.
34. Vendrame M, Zarowski M, Loddenkemper T, Steinborn B, Kothare
SV. Selective serotonin reuptake inhibitors and periodic limb movements
of sleep. Pediatr Neurol. 2011;45(3):175–7.
35. Rottach KG, Schaner BM, Kirch MH, Zivotofsky AZ, Teufel LM, Gallwitz
T, Messer T. Restless legs syndrome as side effect of second generation
antidepressants. J Psychiatr Res. 2008;43(1):70–5.
36. Nofzinger EA, Fasiczka A, Berman S, Thase ME. Bupropion SR reduces peri-
odic limb movements associated with arousals from sleep in depressed patients
with periodic limb movement disorder. J Clin Psychiatry. 2000;61(11):858.
37. Bayard M, Bailey B, Acharya D, Ambreen F, Duggal S, Kaur T, Rahman
ZU, Roller K, Tudiver F. Bupropion and restless legs syndrome: a random-
ized controlled trial. J Am Board Fam Med. 2011;24(4):422–8.
38. Davis ID, Baron J, O'riordan MA, Rosen CL. Sleep disturbances in pedi-
atric dialysis patients. Pediatr Nephrol. 2005;20(1):69–75.
39. Sinha R, Davis ID, Matsuda-Abedini M. Sleep disturbances in children
and adolescents with non-dialysis-dependent chronic kidney disease. Arch
Pediatr Adolesc Med. 2009;163(9):850–5.
40. Merlino G, Lorenzut S, Gigli GL, Romano G, Montanaro D, Moro A,
Valente M. A case–control study on restless legs syndrome in nondialyzed
patients with chronic renal failure. Mov Disord. 2010;25(8):1019–25.
41. Araujo SM, de Bruin VM, Nepomuceno LA, Maximo ML, Daher Ede F,
Correia Ferrer DP, de Bruin PF. Restless legs syndrome in end-stage renal
disease: clinical characteristics and associated comorbidities. Sleep Med.
2010;11(8):785–90.
42. Aritake-Okada S, Nakao T, Komada Y, Asaoka S, Sakuta K, Esaki S,

Nomura T, Nakashima K, Matsuura M, Inoue Y. Prevalence and clinical
characteristics of restless legs syndrome in chronic kidney disease patients.
Sleep Med. 2011;12(10):1031–3.
43. Winkelmann J, Stautner A, Samtleben W, Trenkwalder C. Long-term
course of restless legs syndrome in dialysis patients after kidney transplan-
tation. Mov Disord. 2002;17(5):1072–6.
44. Trenkwalder C, Paulus W. Restless legs syndrome: pathophysiology, clin-
ical presentation and management. Nat Rev Neurol. 2010;6(6):337–46.
45. Bega D, Malkani R. Alternative treatment of restless legs syndrome: an
overview of the evidence for mind-body interventions, lifestyle interven-
tions, and neutraceuticals. Sleep Med. 2016;17:99–105.
46. Aukerman MM, Aukerman D, Bayard M, Tudiver F, Thorp L, Bailey
B. Exercise and restless legs syndrome: a randomized controlled trial.
J Am Board Fam Med. 2006;19(5):487–93.
47. Lettieri CJ, Eliasson AH. Pneumatic compression devices are an effective
therapy for restless legs syndrome: a prospective, randomized, double-
blinded, sham-controlled trial. Chest. 2009;135(1):74–80.
48. Mitchell UH. Nondrug-related aspect of treating Ekbom disease, formerly
known as restless legs syndrome. Neuropsychiatr Dis Treat. 2011;7:251–7.
49. Silber MH, Becker PM, Earley C, Garcia-Borreguero D, Ondo WG,
Medical Advisory Board of the Willis-Ekbom Disease Foundation. Willis-
Ekbom Disease Foundation revised consensus statement on the manage-
ment of restless legs syndrome. Mayo Clin Proc. 2013;88(9):977.
50. Walters AS, Mandelbaum DE, Lewin DS, Kugler S, England SJ, Miller
M. Dopaminergic therapy in children with restless legs/periodic limb
movements in sleep and ADHD. Dopaminergic Therapy Study Group.
Pediatr Neurol. 2000;22(3):182–6.
51. Guilleminault C, Palombini L, Pelayo R, Chervin RD. Sleepwalking and
sleep terrors in prepubertal children: what triggers them? Pediatrics.
2003;111(1):e17–25.
52. Simakajornboon N, Kheirandish-Gozal L, Gozal D. Diagnosis and man-
agement of restless legs syndrome in children. Sleep Med Rev.
2009;13:149–56.
53. Erichsen D, Ferri R, Gozal D. Ropinirole in restless legs syndrome and
periodic limb movement disorder. Ther Clin Risk Manag. 2010;6:173–82.
54. Kotagal S, Silber MH. Childhood-onset restless legs syndrome. Ann
Neurol. 2004;56(6):803–7.
55. Picchietti MA, Picchietti DL. Restless legs syndrome and periodic limb
movement disorder in children and adolescents. Semin Pediatr Neurol.
2008;15(2):91–9.
56. Kalantar-Zadeh K, Kalantar-Zadeh K, Lee GH. The fascinating but decep-
tive ferritin: to measure it or not to measure it in chronic kidney disease?
Clin J Am Soc Nephrol. 2006;1 Suppl 1:S9–18.
57. Scholz H, Trenkwalder C, Kohnen R, Riemann D, Kriston L, Hornyak
M. Dopamine agonists for restless legs syndrome. Cochrane Database
Syst Rev. 2011;3, CD006009.
58. Aurora RN, Kristo DA, Bista SR, Rowley JA, Zak RS, Casey KR, Lamm
CI, Tracy SL, Rosenberg RS, American Academy of Sleep Medicine. The
treatment of restless legs syndrome and periodic limb movement disorder
in adults—an update for 2012: practice parameters with an evidence-
based systematic review and meta-analyses: an American Academy of
Sleep Medicine Clinical Practice Guideline. Sleep. 2012;35(8):1039.
59. Montagna P, Sassoli de Bianchi L, Zucconi M, Cirignotta F, Lugaresi
E. Clonazepam and vibration in restless legs syndrome. Acta Neurol
Scand. 1984;69(6):428.
60. Montplaisir J, Godbout R, Boghen D, DeChamplain J, Young SN, Lapierre
G. Familial restless legs with periodic movements in sleep: electrophysi-
ologic, biochemical, and pharmacologic study. Neurology. 1985;35(1):130.
61. Narowska D, Bożek M, Krysiak K, Antczak J, Holka-Pokorska J,
Jernajczyk W, Wichniak A. Frequent difficulties in the treatment of rest-
less legs syndrome—case report and literature review. Psychiatr Pol.
2015;49(5):921–30.
62. Becker PM, Novak M. Diagnosis, comorbidities, and management of rest-
less legs syndrome. Curr Med Res Opin. 2014;30(8):1441–60.
63. Ferini-Strambi L, Marelli S. Pharmacotherapy for restless legs syndrome.
Expert Opin Pharmacother. 2014;15(8):1127–38.
64. Wijemanne S, Jankovic J. Restless legs syndrome: clinical presentation
diagnosis and treatment. Sleep Med. 2015;16(6):678–90.
65. Liu GJ, Wu L, Lin Wang S, Xu LL, Ying Chang L, Fu Wang Y. Efficacy of
pramipexole for the treatment of primary restless leg syndrome: a system-
atic review and meta-analysis of randomized clinical trials. Clin Ther.
2016;38(1):162–79.
66. Rosen CL, Palermo TM, Larkin EK, Redline S. Health-related quality of
life and sleep-disordered breathing in children. Sleep. 2002;25(6):657–66.
67. O'Brien LM, Gozal D. Neurocognitive dysfunction and sleep in children:
from human to rodent. Pediatr Clin North Am. 2004;51(1):187–202.
68. Szentkiralyi A, Molnar MZ, Czira ME, Deak G, Lindner AV, Szeifert L,
Torzsa P, Vamos EP, Zoller R, Mucsi I, Novak M. Association between
restless legs syndrome and depression in patients with chronic kidney dis-
ease. J Psychosom Res. 2009;67(2):173–80.
69. Roumelioti ME, Wentz A, Schneider MF, Gerson AC, Hooper S, Benfield
M, Warady BA, Furth SL, Unruh ML. Sleep and fatigue symptoms in chil-
dren and adolescents with CKD: a cross-sectional analysis from the
chronic kidney disease in children (CKiD) study. Am J Kidney Dis.
2010;55(2):269–80.
70. Davis ID, Greenbaum LA, Gipson D, Wu LL, Sinha R, Matsuda-Abedini
M, Emancipator JL, Lane JC, Hodgkins K, Nailescu C, Barletta GM,
Arora S, Mahan JD, Rosen CL. Prevalence of sleep disturbances in chil-
dren and adolescents with chronic kidney disease. Pediatr Nephrol.
2012;27(3):451–9.
Obstructive Sleep Apnea
in Adolescence 4
Stacey Gunn and Umakanth A. Khatwa
Abbreviations
AAP American Academy of Pediatrics

AASM American Academy of Sleep Medicine
AAO-HNSF American Academy of Otolaryngology and Head
and Neck Surgery
AHI Apnea-hypopnea index
BMI Body mass index
CPAP Continuous positive airway pressure
DISE Drug-induced sleep endoscopy
ICSD-3 International Classification of Sleep Disorders
3rd edition
PSG Polysomnography
NREM Non-rapid eye movement sleep
REM Rapid eye movement sleep
S. Gunn, M.D.
Division of Pulmonary, Critical Care and Sleep, Beth Israel Deaconess
Medical Center, Boston, MA, USA
U.A. Khatwa, M.D. (*)
Division of Respiratory Diseases, Department of Medicine,
Boston Children’s Hospital, 333 Longwood Ave, LO486,
Boston, MA 02115, USA
e-mail: umakanth.khatwa@childrens.harvard.edu

46 S. Gunn and U.A. Khatwa
Clinical Case 1
Jacob is a 14 year-old generally healthy teenage boy, presenting

with a 2 years history of excessive daytime sleepiness, with difficulty
focusing on his schoolwork, and a tendency to fall asleep during
afternoon classes. His mother is unable to say definitively whether
he snores. Jacob's bedtime is 10:30 pm on weeknights, and he uses
his iPad until he falls asleep around midnight. He has a hard time
waking up in the morning for school, which starts at 7 am. On the
weekends, he sleeps from 2 am until 11 am.
On physical examination, he is well-appearing, of normal
weight (BMI 22 kg/m2), with a Mallampati class II airway, and 3+
tonsils. There is no micrognathia, retrognathia, or hyponasality.
The nasal septum is midline and nasal turbinates are not enlarged.
With concern for obstructive sleep apnea, overnight polysom-
nography was ordered to confirm the diagnosis and establish dis-
ease severity. In preparation, sleep hygiene recommendations
were made, including limiting exposure to electronics before bed,
and keeping a consistent sleep schedule between weekdays and
weekends. Polysomnography was notable for severe obstructive
sleep apnea, with AHI 21 events per hour and O2 saturation nadir
91 %, and was also notable for a prolonged sleep onset latency of
62.5 min, and a delayed REM onset latency of 154.0 min.
The patient was scheduled for adenotonsillectomy which he
tolerated well, and was discharged to home the following day.
A repeat polysomnogram 8 weeks postoperatively demonstrated a
reduction in the residual AHI to 2 events per hour. At follow-up, he
reported better daytime energy levels and was no longer falling
asleep in class.
Discussion
Based on this patient’s presentation, there is a reasonably high sus-

picion for obstructive sleep apnea as a contributor to his excessive
daytime sleepiness. Typical signs and symptoms that raise concern
for obstructive sleep apnea are outlined in Table 4.1. A careful his-
tory must be taken in this age group, as a history of snoring is not
4 Obstructive Sleep Apnea in Adolescence 47
Table 4.1 Features associated with obstructive sleep apnea in adolescents

Physical Adenotonsillar hypertrophy, obesity, enlarged tongue (broad
exam tongue base, scalloping), increased neck circumference, nasal
findings septal deviation, enlarged nasal turbinates, craniofacial
abnormalities, swollen mucous membranes, deviated nasal
septum, adenoid facies (elongated midface, mouth-breathing,
and infraorbital darkening), high-arched palate, dental overjet,
posterior buccal cross-bite, crowded oropharynx, midface
hypoplasia, micrognathia, retrognathia, African American race,
male sex
Comorbid Neuromuscular disease, genetic syndromes, exposure to
medical tobacco, environmental allergies, asthma, GERD,
disease hypertension, enuresis, bruxism
Nighttime Snoring, witnessed apneas, gasping/choking arousals,
features increased work of breathing, mouth-breathing, restless sleep
Daytime Nasal congestion, excessive daytime sleepiness, morning
features headaches, waking with a dry mouth, attentional difficulties,
hyperactivity, aggressive behavior, poor school performance
always present, and surprisingly is often not the presenting clinical

complaint. More often, it is subtle symptoms of daytime fatigue or
sleepiness, inattentiveness, or poor school performance, that bring
the patient to clinical attention. The patient is often not aware of
snoring, and parents are less likely to be aware than they might be
with younger children.
The etiology of excessive daytime sleepiness is often multifac-
torial, and it is important to address all potential factors that could
contribute to sleep fragmentation or reduced sleep quality. For this
particular patient, the factors that are contributing to his daytime
symptoms include obstructive sleep apnea, a circadian rhythm
delay, and poor behavioral sleep practices (often referred to as
“sleep hygiene”). Attention to a circadian phase delay should not
be overlooked, as sleep apnea and circadian delay tendencies are
often comorbid in this patient population, and symptoms of day-
time fatigue and sleepiness will not be adequately treated if all
aspects of the patient’s sleep disorder are not addressed. Please see
the chapter on circadian disorders in adolescents for a full discus-
sion on identification and management of shifts in the internal
body clock.
Prior to performing an overnight sleep study, it is prudent to

institute sleep hygiene recommendations to increase the likelihood
that an adequate duration of sleep will be able to be obtained on the
night of the study. Both the American Academy of Pediatrics (AAP)
and the American Academy of Sleep Medicine (AASM) recom-
mend routine use of the PSG for diagnosis of sleep apnea, being that
the sensitivity and specificity of the history and physical examina-
tion are poor, and tonsillar size is not necessarily predictive of the
presence of OSA [1, 2]. For example, the sensitivity and specificity
of witnessed apneic events as a predictor of OSA ranges anywhere
from 47–88 % and 17–90 %, respectively. The sensitivity and speci-
ficity of tonsillar hypertrophy (grade 3+ to 4+) as a predictor of
OSA ranges anywhere from 12–93 % and 35–89 %, respectively
[3]. There are no screening tests or combined metrics that have yet
been validated for reliable diagnosis of OSA, and polysomnogra-
phy remains the gold standard. A potential source of confusion for
clinicians is that the surgical guidelines issued by the American
Academy of Otolaryngology-Head and Neck Surgery (AAO-
HNSF) allow for tonsillectomy to be performed without a preopera-
tive PSG unless the need for surgery is uncertain, reported symptoms
are out of proportion to tonsillar size, or certain other clinical crite-
ria are present; including obesity, Down syndrome, craniofacial
abnormalities, neuromuscular disorders, sickle cell disease, or
mucopolysaccharidoses [4].
At our institution, preoperative polysomnography prior to ade-
notonsillectomy is usually considered in adolescents for several
reasons. (1) Determining the severity of OSA is useful in guiding
perioperative and postoperative management (day surgery vs inpa-
tient vs ICU admission), risk stratifying for perioperative compli-
cations, estimating the likelihood of residual disease, and guiding
the decision whether to obtain follow-up polysomnography.
Preoperative PSG can also allow for avoidance of unnecessary or
ineffective surgery in patients with primarily non-obstructive events.
In less-severe cases of sleep apnea in adolescents, it is not clear
whether to apply pediatric criteria or “adult” criteria for a diagno-
sis of OSA. According to the ICSD-3, pediatric scoring criteria
(obstructive AHI > 1 event per hour or a pattern of obstructive
hypoventilation) may be used until age 18, although between ages
13 and 18 there is an option to use adult criteria (obstructive
AHI > 5 events per hour) [5]. This decision depends on the clinical
context of the individual patient.
Patients with mild or moderate degrees of sleep apnea (less than
10 events per hour) may be at acceptable risk to undergo day sur-
gery. Patients with severe OSA, defined as AHI > 10 events per
hour, or severe gas exchange abnormalities (oxygen saturation
nadir <80 % or significant hypoventilation), are at higher risk for
postoperative complications and should be monitored at least over-
night in an inpatient setting. The most common complications
associated with adenotonsillectomy are pain and poor oral intake,
with more severe complications including hemorrhage, infection,
and respiratory decompensation. Risk factors for pulmonary
complications following adenotonsillectomy in the adolescent age
group include severe OSA (AHI > 10 events per hour, SpO2 nadir
<80 %, or significant hypoventilation), morbid obesity, neuromus-
cular disease, pulmonary hypertension, Down syndrome, craniofa-
cial abnormalities, asthma, sickle cell disease, congenital heart
disease, or a history of respiratory compromise. Respiratory
decompensation is associated with higher baseline AHI, higher
BMI z-score, and lower O2 saturation nadir [6].
Following adenotonsillectomy, all patients should be reassessed
clinically for residual symptoms. A follow-up PSG is indicated
when there was moderate-to-severe disease preoperatively, or fac-
tors associated with an increased risk of residual OSA, which are
outlined in Table 4.2. The ideal timing of a follow-up study is
2–3 months, to allow an appropriate postoperative recovery period,
but also protect the patient from prolonged periods of untreated
apnea in the event of residual disease.
Pitfalls
– Snoring is often not the presenting complaint in adolescents

with concern for obstructive sleep apnea, and evaluation
should include assessment for subtle signs of sleep disordered
breathing.
– Failure to recognize and address the comorbid circadian factors,
poor sleep hygiene, and sleep restriction is not unusual in this
age group. Often, both OSA and a delayed circadian sleep phase
can coexist and contribute to excessive daytime sleepiness.
Table 4.2 Factors associated with high risk of residual OSA in adolescents
High preoperative AHI (AHI > 10/h)
Obesity (BMI > 30)
Underbite, overbite, crossbite
Severe allergic rhinitis (hypertrophic turbinates, regrown adenoids)
Neuromuscular weakness
Glossoptosis
Craniofacial syndromes
Lingual tonsillar hypertrophy
Occult laryngomalacia
Age-related increased upper airway collapsibility
Adenoid facies
Micrognathia
Age of adenotonsillectomy > 7 years
Learning Points
– There are no physical exam features or screening metrics that can

reliably rule-in or rule-out a diagnosis of obstructive sleep apnea
and clinical assessment does not predict the severity of the under-
lying OSA. In-lab polysomnography remains the gold standard.
– Even with a high suspicion of obstructive sleep apnea, preop-
erative PSG should still be performed prior to adenotonsillec-
tomy, as knowledge of disease severity is important for risk
stratification and perioperative management.
– If there is evidence for severe sleep apnea (based on a high
index of events per hour, or substantial gas exchange abnor-
malities), then inpatient postoperative monitoring is indicated
due to the high rates of pulmonary complications.
Clinical Case 2
Peter is an obese 16-year-old boy (BMI 31 kg/m2), presenting with

reports of loud snoring, witnessed apneas, and excessive daytime
sleepiness. Physical examination revealed a Mallampati class II
airway, with 2+ tonsillar hypertrophy. The nasal septum was mid-
line, without significant turbinate hypertrophy. He underwent diag-
nostic polysomnography and was found to have severe obstructive
sleep apnea with AHI of 40 events per hour, and O2 saturation nadir
87 %. He underwent adenotonsillectomy, tolerated the procedure
well, had an uneventful postoperative recovery, and was discharged
to home the following day.
In 2-month follow-up, his mother noted that he continued to
snore, and his symptoms of daytime sleepiness had not improved.
His weight had increased from prior, to BMI 32.5 kg/m2. On follow-
up PSG, he had a high residual AHI of 22 events per hour. CPAP
was titrated from 5–12 cm H2O, with 8 cm H2O appearing optimal
to relieve obstruction. He was started on therapy with CPAP 8 cm
H2O, recommended to sleep in non-supine positioning, and encour-
aged to focus on weight loss. He was also referred for otolaryngol-
ogy evaluation, and there were no clear sites of anatomic
obstruction observed on flexible nasolaryngoscopy in the clinic.
At his follow-up visit one month later, he had good compliance with
CPAP, with use on more than 80 % of nights, and reported improve-
ment in his daytime energy levels. A plan was made to continue CPAP
therapy, in conjunction with efforts at weight loss.
Discussion
Rates of residual obstructive sleep apnea following adenotonsillec-

tomy vary depending on the AHI threshold used, but have been
reported as high as 73 % when including obese patients and adoles-
cents and using the more stringent cutoff of AHI ≥ 1 per hour, under-
scoring the importance of follow-up testing. Factors associated with
residual OSA following adenotonsillectomy were discussed above.
OSA in adolescents is thought to result from a combination of
enlargement in lymphoid tissue, obesity, and reduction in neuro-
muscular tone and neuromotor reflexes. The Pcrit, or pharyngeal
closing pressure (a measure of upper airway collapsibility),
becomes less negative in adolescents as upper airway motor neuron
reflexes decline, and differences in neuromuscular responsiveness
between individuals might explain why some obese adolescents
develop sleep apnea and others do not [7]. An important question
in the adolescent population is whether the pathophysiology of
obstructive sleep apnea is more similar to children, with hypertro-
phic lymphoid tissue being the primary etiologic factor (in the
absence of craniofacial structural abnormalities), or whether the
abnormality is more similar to adults, with obesity-related ana-

tomic risk factors (enlargement of the parapharyngeal fat pads,
tongue, lateral pharyngeal walls, and total upper airway soft tissue
volume). Although tonsils typically regress in children beginning
around age 8, tonsillar tissue has been shown to continue to increase
in size in the presence of snoring. An MRI-based study comparing
anatomic features of obese adolescents (age 12–16 years) with
sleep apnea to both obese controls without sleep apnea and to lean
controls, demonstrated that lymphoid hypertrophy (rather than soft
tissue enlargement) is the predominant anatomic risk factor [8].
There is a tendency in clinical practice to underestimate the contri-
bution of the tonsils to obstructive sleep apnea in the adolescent
age group and move directly to CPAP without first performing
adenotonsillectomy. It is important to recognize that tonsillar
hypertrophy might still be contributing significantly despite the
presence of obesity, and that adenotonsillectomy remains first-line
treatment. It should be noted that adenotonsillectomy has been
associated with short-term weight gain, likely due to changes in
hormonal regulation [9–11].
When CPAP is recommended, compliance is often poor, and
hence most of these patients go untreated. Several common prob-
lems noted with CPAP and methods for troubleshooting are listed
in Table 4.3.
Weight loss has been shown to reduce apnea burden, although
sustained weight loss is often difficult to achieve [9]. Bariatric sur-
gery is a consideration in appropriately selected patients who are
morbidly obese, who fail diet and exercise treatment, and have
associated comorbid conditions such as diabetes, hypertension, and
OSA. Non-supine sleep is helpful as a complementary measure to
keep the airway open. Rapid maxillary expansion often is not an
option in the adolescent population, once the hard palate has already
fused. Surgical interventions, such as mandibular distraction osteo-
genesis, can be considered in select patients with craniofacial syn-
dromes. There is minimal data regarding the use of oral appliances
(mandibular advancement devices) in adolescents, and they are not
widely used due to concerns regarding dental malocclusion.
Obesity hypoventilation syndrome is characterized by obesity
(BMI > 30) and hypercapnic respiratory insufficiency (wake
PaCO2 > 45 mmHg), not secondary to other causes (neuromuscular,
Table 4.3 Troubleshooting commonly encountered problems with CPAP

Nasal dryness or congestion Treat with nasal steroids or heated humidity
Claustrophobia Change from a full facemask to a lower
profile model (nasal mask or nasal pillows)
Anxiety Mask habituation/desensitization; using the
mask for short periods of time during the day
Leak/mouth-breathing Use a full facemask or add a chinstrap
Pressure intolerance Add a ramp setting or EPR
(expiratory pressure relief)
Eye irritation (from mask fit Treat by changing or adjusting the mask
or air leak) (which should be a snug fit, but not
be too tight)
Skin irritation or breakdown Treat by changing the mask, or adding
over the nasal bridge or nares hydrocolloid gel cushions
Epistaxis Change the mask or adjust the humidity,
depending on the suspected cause of irritation
Gastric distention due to Treat by lowering the pressure setting,
aerophagia adding flex or expiratory pressure relief
settings, or sleeping with the head of the
bed elevated
metabolic, lung, or chest wall disease). OHS is important to recog-

nize because of the association with pulmonary hypertension and
development of right heart failure. More than 90 % of patients with
OHS have comorbid OSA. Treatment consists of noninvasive noc-
turnal ventilation, using either BiPAP or CPAP, in conjunction with
concerted efforts at weight loss [12].
Pitfalls
– In the setting of obesity and moderately enlarged tonsils, there is a

tendency to attribute the disordered breathing to the excess weight,
and minimize the component of lymphoid hypertrophy, with a
resultant inappropriate tendency to avoid surgical intervention.
– CPAP noncompliance rates are high across all patients, particu-
larly in adolescents. A team approach with a focus on psycho-
social aspects can help improve compliance rates and PAP
adherence.
Learning Points
– Adenotonsillectomy remains first-line treatment for obstructive

sleep apnea in adolescents, even in the setting of obesity.
– Weight loss is an important element of treatment for sleep
apnea in obese patients, although sustained weight loss is dif-
ficult to achieve, and adenotonsillectomy is associated with
short-term weight gain.
– Although the incidence of OHS is infrequent in this population,
it is important to recognize and treat to prevent serious cardio-
pulmonary consequences.
Clinical Case 3
Johnny is a 16-year-old obese African American boy, who initially

presented with snoring, witnessed apneas, gasping arousals, and
excessive daytime sleepiness. Physical exam was notable for obe-
sity (BMI 35 kg/m2), mild hypertension (BP 134/86 mmHg),
enlarged neck circumference of 17 in., and signs of insulin resis-
tance (acanthosis nigricans). His airway was crowded; Mallampati
class IV with grade 3+ tonsils, an enlarged tongue, a mild degree
of overbite, and enlarged nasal turbinates. Auscultation of the
chest was normal, as was the remainder of the physical
examination.
PSG demonstrated severe supine and REM-dominant OSA, with
overall AHI of 36 events per hour and O2 saturation nadir 82 %.
End-tidal CO2 levels ranged from 45–58 mmHg. Given the severity
of disease, he was admitted and started empirically on CPAP,
while awaiting urgent adenotonsillectomy with nasal turbinate
reduction. Postoperatively, he was noted to have hypoxemia, and
chest x-ray was notable for slight haziness consistent with mild
pulmonary edema. He was started on CPAP and diuretics and
improved over the next 48 h. He was discharged on hospital day 4,
with CPAP 8 cm H2O.
In follow-up after 4 weeks, he reported that he was unable to
tolerate CPAP and had stopped using it. He changed the mask to
nasal pillows and was prescribed nasal saline and steroid sprays.
He was scheduled for a repeat sleep study, with the baseline por-
tion notable for a high residual OAHI of 26 events per hour, again
with moderate desaturations and elevated CO2. On titration, 8 cm
H2O relieved obstruction in lateral NREM, although 13 cm H2O
could not completely eliminate obstruction in supine REM, and
the patient was unable to sleep at higher pressures. He was pre-
scribed AutoCPAP 8–13 cm H2O with a recommendation for non-
supine sleep.
In follow-up 6 weeks later, he reported ongoing difficulty toler-
ating CPAP, only able to tolerate therapy for 1–2 h per night. He
was scheduled for drug-induced sleep endoscopy (DISE), which
revealed significantly enlarged nasal turbinates blocking 90 % of
the nostrils, with a deviated nasal septum causing complete
obstruction of the right-sided nasal passage. There was adenoidal
regrowth, with more than 50 % obstruction. There was a signifi-
cant degree of tongue base obstruction with complete blockage,
and markedly enlarged 4+ lingual tonsils completely closing the
laryngeal inlet. The epiglottis was omega-shaped and retroflexed.
On jaw thrust maneuver, the airway opened nicely, and the vocal
cords were seen to have normal movement.
Based on the results of this procedure, the patient underwent
upper airway surgery, which included turbinectomy, nasal septo-
plasty, revision adenoidectomy, and lingual tonsillectomy. He tol-
erated the procedure well and was discharged to home with
AutoCPAP 5–10 cm H2O.
Repeat polysomnography 8 weeks later demonstrated good
reduction in the residual AHI to 4.8 events per hour, with O2 satu-
ration nadir 92 %. The patient reported less daytime sleepiness
and an improved attention span. He had lost 3 kg after enrolling in
a weight loss program. CPAP was able to be discontinued.
Discussion
There are multiple risk factors present that put this patient at a high
risk for perioperative complications (see previous discussion), and
he was appropriately admitted to the hospital for urgent initiation of
CPAP and adenotonsillectomy, then to the intensive care unit for
postoperative monitoring. Because of the presence of pulmonary

complications in the postoperative period, as well as the high level
of suspicion that there would be residual disease, it was recom-
mended that this patient continue to use CPAP at home until follow-
up. Residual apnea was confirmed to be present on his follow-up
study, which also allowed for titration on positive pressure therapy.
The inability of even high levels of positive pressure to completely
relieve his obstruction increased the level of suspicion that there
would be a prominent degree of mechanical airway obstruction
when the airway was directly visualized.
Drug-induced sleep endoscopy is a procedure using a flexible
fiberoptic endoscope inserted trans-nasally. The patient is placed
under light sedation and breathes spontaneously, in an effort to
recreate natural sleep, with the goal of observing dynamic airway
collapse throughout the pharynx in order to determine the site of
airway obstruction, to identify appropriate surgical targets.
Potential indications for DISE include patients with documented
OSA but small tonsils on clinical exam, or those with residual
OSA after adenotonsillectomy (particularly patients with poor tol-
erance of CPAP or high pressure requirements). DISE often identi-
fies multilevel airway collapse. Sites of airway obstruction that can
be visualized on DISE are outlined in Table 4.4. The data regard-
ing outcomes is limited at the present time, although a small study
of patients with residual OSA following adenotonsillectomy who
Table 4.4 Common sites of airway obstruction identified on DISE

Nasal polyps
Nasal turbinate hypertrophy
Nasal septal deviation
Adenoidal regrowth
Retro-palatal collapse
Redundant uvula or soft palate
Lingual tonsillar hypertrophy
Hypopharyngeal base of tongue collapse
Oropharyngeal wall collapse (lateral, anterior-to-posterior, or concentric)
Occult or sleep-state-dependent laryngomalacia
Epiglottic collapse
Vocal cord paralysis
underwent DISE-directed operative management demonstrated

substantial improvement in subjective measures of sleep and a
trend towards improvement in AHI [13]. As more centers become
familiar with the techniques of DISE and are better able to target
the specific site of airway obstruction on an individual basis, it is
anticipated that rates of successful treatment response will con-
tinue to improve.
Pitfalls
– The finding of severe gas exchange abnormalities and high dis-

ease burden should prompt an inpatient admission for initiation
of CPAP as bridging therapy, followed by urgent tonsillectomy.
– Poor CPAP compliance might be related to anatomic factors
making use difficult and should not be dismissed as willful
noncompliance.
Learning Points
– Drug-induced sleep endoscopy is a valuable method for identi-

fying residual sites of airway collapse, which may be targets for
further surgical intervention, when the traditional treatment
pathway fails to effectively treat the patient.
Conclusion
Care of the adolescent with sleep-disordered breathing requires

the clinician to carefully assess for sleep apnea, obtain diagnostic
information (in the form of a polysomnogram) in order to appro-
priately triage, and continue to follow-up the patient until there is
adequate resolution of disease. Management of sleep apnea in ado-
lescents is a challenge because the cases often do not fit neatly into
the previously well-defined pediatric or adult pathways. Despite
high rates of residual apnea following adenotonsillectomy in ado-
lescents, this remains first-line therapy. When residual apnea is
present, then further treatment with CPAP should be utilized.
DISE can be instrumental in identifying anatomic sites of airway

collapse and guiding multilevel upper airway surgery. The ability
of DISE to guide interventions to be tailored to the individual
patient is promising, as a relatively novel method to offer targeted
and effective therapy.

manuscript.
References
1. Marcus CL, Brooks LJ, Ward SD, Draper KA, Gozal D, Halbower AC,
et al. Diagnosis and management of childhood obstructive sleep apnea
syndrome. Pediatrics. 2012;130(3):e714–55.
2. Kothare SV, Rosen CL, Lloyd RM, Paruthi S, Thomas SM, Troester MM,
et al. Quality measures for the care of pediatric patients with obstructive
sleep apnea. J Clin Sleep Med. 2015;11(3):385–404.
3. Brietzke SE, Katz ES, Roberson DW. Can history and physical examina-
tion reliably diagnose pediatric obstructive sleep apnea/hypopnea syn-
drome? A systematic review of the literature. Otolaryngol Head Neck
Surg. 2004;131:827–32.
4. Roland PS, Rosenfeld RM, Brooks LJ, Friedman NR, Jones J, Kim TW,
Kuhar S, Mitchell RB, Seidman MD, Sheldon SH, Jones S, Robertson
P. Clinical practice guideline: polysomnography for sleep-disordered
breathing prior to tonsillectomy in children. Otolaryngol Head Neck Surg.
2011;145 Suppl 1:S1–15.
5. American Sleep Disorders Association. International classification of
sleep disorders: diagnostic and coding manual. Rochester, MN: American
Sleep Disorders Association; 2014.
6. Jaryszak EM, Shah RK, Vanison CC, et al. Polysomnographic variables
predictive of adverse respiratory events after pediatric adenotonsillec-
tomy. Arch Otolaryngol Head Neck Surg. 2011;137(1):15–8.
7. Huang J, Pinto SJ, Yuan H, et al. Upper airway collapsibility and genio-
glossus activity in adolescents during sleep. Sleep. 2012;35(10):1345–52.
doi:10.5665/sleep.2110.
8. Schwab RJ, Kim C, Bagchi S, Keenan BT, Comyn F-L, Wang S, et al.
Understanding the anatomic basis for obstructive sleep apnea syndrome in
adolescents. Am J Respir Crit Care Med. 2015;191(11):1295–309.
9. Verhulst SL, Franckx H, Van Gaal L, De Backer W, Desager K. The effect
of weight loss on sleep-disordered breathing in obese teenagers. Obesity.
2009;17(6):1178–83.
10. Alqahtani AR, Elahmedi MO, Al Qahtani A. Co-morbidity resolution in

morbidly obese children and adolescents undergoing sleeve gastrectomy.
Surg Obes Relat Dis. 2014;10(5):842–50.
11. Van M, Khan I, Hussain SSM. Short-term weight gain after adenotonsil-
lectomy in children with obstructive sleep apnoea: systematic review.
J Laryngol Otol. 2016;130(03):214–8.
12. Shetty S, Parthasarathy S. Obesity hypoventilation syndrome. Curr
Pulmonol Rep. 2015;4(1):42–55. doi:10.1007/s13665-015-0108-6.
13. Wootten CT, Chinnadurai S, Goudy SL. Beyond adenotonsillectomy: out-
comes of sleep endoscopy-directed treatments in pediatric obstructive
sleep apnea. Int J Pediatr Otorhinolaryngol. 2014;78(7):1158–62.
Narcolepsy in Adolescence
5
Anne Marie Morse and Sanjeev V. Kothare
Abbreviations
ADHD Attention deficit hyperactivity disorder

DSPD Delayed sleep phase disorder
EDS Excessive daytime sleepiness
HCG Human chorionic gonadotropin hormone
MAOI-B Monoamine oxidase inhibitory subtype B
MSLT Multiple sleep latency test
PLMs Periodic leg movements
PSG Polysomnography
RBD Rapid eye movement sleep behavioral disorder
REM Rapid eye movement
SE Sleep efficiency
SL Sleep latency
SOREM Sleep onset REM
A.M. Morse, M.D.

Division of Sleep Medicine—Neurology, Montefiore Medical Center,
Bronx, NY, USA
e-mail: drannemorse@gmail.com
New York, NY, USA

62 A.M. Morse and S.V. Kothare
Clinical Case 1
Justin is a 15-year-old young man presenting to our clinic with his

mother secondary to concerns of poor school performance, inat-
tentiveness, and motor tics. The mother reports that she and the
school were concerned that he may have ADHD, and this may be
the reason he is at risk for failing this year. In addition, he has
developed paroxysmal motor behaviors thought to be a motor tic
that is most prominent when he laughs, mainly with facial involve-
ment. Further history reveals that prior to this year, he has never
had any difficulty with school, has always been an honor roll stu-
dent, rarely missed assignments and usually completed tasks more
quickly than his peers. There is no history of hyperactivity.
Justin states that since the end of summer he has gained weight
and has felt exhausted. He could easily fall asleep at any time, but
generally has a hard time staying asleep. He agrees with his mother
that he finds it very difficult to focus, even when he feels more
awake. He states that he is not certain about the tics his mom
describes, but he does experience pins and needles sensation in his
hands with laughter and he tends to drop things, most recently his
cell phone, cracking the screen.
Physical exam reveals an overweight teenager, but is otherwise
unremarkable and neurologically intact.
After evaluating the Vanderbilt scales completed by the school
and parents, he is given a diagnosis of ADHD—inattentive type
and started on dextroamphetamine 30 mg daily. At follow-up, he
feels more awake and alert. No change in frequency of motor com-
plaints and has persistent sleep fragmentation. Additionally, he
describes a recent episode of collapsing with loss of conscious-
ness, when he was getting ready to go into a baseball game as a
relief pitcher.
Discussion
The patient above has received a diagnosis of ADHD, but the

symptoms described are more suggestive of narcolepsy with cata-
plexy. Narcolepsy is defined by clinical features and associated
assessment of cerebrospinal hypocretin 1 (CSF hcrt-1) levels,
5 Narcolepsy in Adolescence 63
thus classifying it into two forms: narcolepsy with cataplexy and/

or CSF hcrt-1 deficiency [narcolepsy type 1 (NT1)], and narco-
lepsy without cataplexy and normal CSF hcrt-1 levels [narco-
lepsy type 2 (NT2)] [1]. Onset usually occurs in adolescence or
young adulthood with a bimodal distribution with peaks at the
age of around 15 and 35 years [2, 3]. In order to diagnose narco-
lepsy clinically, polysomonography and multiple sleep latency
test should be performed to evaluate for a reduced sleep latency
(average </= 8 min) and the presence of 2 or more sleep onset
REM periods. The polysomnogram should not reveal any other
major primary sleep disturbance that can contribute to sleep
deprivation or excessive daytime sleepiness, but may show
PLMS, restless sleep, and/or fragmented sleep, though not enough
to explain the daytime sleepiness. Presence of definite cataplexy
precludes the need for a sleep study or an MSLT though it is often
done to complete the work-up.
Pediatric narcolepsy is frequently undetected and misdiagnosed
[4]. Narcolepsy can be more challenging to identify in the pediatric
age group, as the cataplexy attacks can be subtle, as exhibited in
this case (Table 5.1) [5–8]. For instance, the symptoms considered
Table 5.1 Characterization of cataplexy attacks [5–7]

Part of body Description of event
Head/face Head drop
Sagging of the face or jaw
Slurred speech
Eye lid drooping
Eyebrow raising (compensatory)
Perioral and tongue movements
Tongue thrusting
Upper Dropping items
extremities Difficulty/slurred writing
Abnormal posturing
Trunk Slumping down in seat/loss of postural tone
Body swaying
Lower Buckling of the knees
extremities Difficulty to stand up
Whole body Complete loss of tone and collapse with preserved consciousness
Generalized muscle twitching
to be tics are more consistent with twitching typically seen with

emotion in cataplexy. Cataplexy can be complete, where the symp-
toms are generalized, or partial, where the symptoms are focal or
multifocal. The duration of cataplexy attacks are usually short,
lasting a few seconds to generally less than 2 min [1]. Frequency
of cataplexy is variable, ranging from less than one attack per
month to more than 20 attacks per day [1]. The triggers and symp-
toms can differ from adults, precipitating factors can include
exhaustion, tiredness, and stress and symptoms can be described as
the child having “puppet-like” movements [8].
Frequently, patients with narcolepsy receive several other diag-
noses prior to establishing the correct diagnosis of narcolepsy [9,
10]. In fact, the average time to diagnosis for patients with narco-
lepsy is about 10 years [2, 11]. Many physicians, including sleep
physicians, have difficulty in identifying the pentad of symptoms
of narcolepsy, including excessive daytime sleepiness, hypnogo-
gnic and hypnopompic hallucinations, cataplexy, sleep paralysis,
and disturbed nocturnal sleep [12]. In order to improve recogni-
tion of patients with narcolepsy, the physician should ask appro-
priate screening questions that review at minimum the pentad
symptoms to have a higher yield in recognition. In general, ques-
tioning should start broad and become more detailed to refine the
characteristics and appropriately identify the symptoms being
evaluated for (Table 5.2).
Pitfalls
• Misdiagnosis is common. ADHD, depression, learning disabil-

ities, and even seizures are frequently blamed before narco-
lepsy is recognized.
• Partial cataplexy is more common in children and adolescents
and can be challenging to recognize.
• If symptoms don’t fit or fail to improve with treatment, reevalu-
ate the diagnosis.
Table 5.2 Symptom directed screening questions for narcolepsy

Symptom Example screening questions
Excessive Epworth sleepiness scale
daytime Do you feel sleepy during the day?
sleepiness Do you tend to fall asleep in inactive situations?
Do you feel that sleepiness affects your ability to
participate in school, sports, socializing?
Do short (20–30 min) naps improve your sleepiness/wake
feeling refreshed?
Hypnagogic/ Do you start to dream before you are asleep?
hypnopompic Do you dream during short naps?
hallucinations As you fall asleep or as you are waking up do you ever
feel you hear or see things that are not there?
How frequently do you see things that are not there during
sleep transitions?
Sleep paralysis As you fall asleep or as you are waking out of sleep do
you ever feel paralyzed?
As you are waking from sleep do you ever feel you can’t
move your arms or legs?
If so, is it a frightening experience?
How long does it last?
How frequently does it happen?
Cataplexy Do you ever get any unusual feelings, such as weakness?
Do you find that these are ever associated with emotion?
Do you find laughter, anger, or surprise bring on these
events?
Describe what you experience*
Sleep What time do you go to bed and wake up in the morning?
disruptions How long does it take you to fall asleep?
How many times a night do you wake up?
What is the reason you wake at night?
Associated Do you sleepwalk or sleep talk?
parasomnias Do you have unpleasant or frightening dreams?
Does it every look like you are acting out your dreams?
Does it look like you are fighting in your dreams?
Have you fallen out of bed?
Have you ever injured yourself or anyone else near you
while sleeping because of these behaviors?
Learning Points
• All adolescents that present with symptoms of excessive day-

time sleepiness should be evaluated with a detailed sleep
history.
• Symptoms of narcolepsy include the pentad of excessive day-
time sleepiness, hypnogognic and hypnopompic hallucinations,
cataplexy, sleep paralysis, and disturbed nocturnal sleep.
• Be aware of and inquire about specific symptoms that suggest
cataplexy.
Clinical Case 2
Isaiah is a 14-year-old young man recently diagnosed with narco-

lepsy with cataplexy. He has been started on modafinil for exces-
sive daytime sleepiness and venlafaxine for cataplexy. His father
endorses that his son has more frequent sleep talking, falling out of
bed, and very aggressive behavior during sleep that is concerning
to him. He states that since prior to treatment he had rare occasions
of what looked like restlessness and talking during dreams, but
now since starting treatment he has witnessed frequent episodes
and that in the past week he has even had an episode of falling out
of bed, hitting his head on the corner of a dresser, and sustained a
laceration requiring suture repair.
Discussion
The patient described has features consistent with an REM behav-

ior disorder (RBD). RBD is a movement disorder associated with
loss of REM-related muscle atonia and is characterized by com-
plex, vigorous, and frequently violent dream-enacting behavior
during REM sleep, along with lack of REM atonia on a sleep study
[13]. During these episodes, it is not uncommon for the person
experiencing it to injure themselves or anyone sharing a bed with
them. Patients with narcolepsy have been described to have REM
sleep motor regulation abnormalities that include REM sleep
without atonia, excessive twitching, and periodic leg movements

during sleep (PLMS) [14]. Recent studies on narcolepsy show that
up to 60 % of patients report RBD symptoms and that 43 % had
evidence of RBD during an attended polysomnography [13]. The
Innsbruck narcolepsy cohort, for instance, showed REM without
atonia was present in most patients (100 %) and RBD in 24 % of
patients [15]. Clinical variants include RBD induced or worsened
by pharmacological agents, most of them being used to treat cata-
plexy such as an SSRI, RBD in narcoleptic children de novo and
RBD in the context of symptomatic narcolepsy [16].
Patients with narcolepsy with cataplexy being treated with
antidepressants have a three-fold higher occurrence of RBD in
comparison to antidepressant-naïve patients [17]. In medication
induced RBD, the initial appropriate intervention would be to
withdraw or change treatment. Treatment available for RBD
include clonazepam, melatonin, and sometimes pramipexole;
however, there is a lack clinical trials evaluating use specifically
for RBD in narcoleptic patients [16]. Recognition and modifica-
tion of treatment of RBD in patients with narcolepsy is impor-
tant. However, it should be anticipated that RDB may occur and
the family should be educated on creating a safe sleep environ-
ment (Table 5.3) to prevent injury. Switching to bupropion could
reduce the risk for worsening cataplexy and periodic limb move-
ments of sleep.
Table 5.3 Safe sleep environment

Maintaining a safe sleep environment
• Place mattress on the floor (i.e., sleep close to ground) or padded water beds
• Pad corners of furniture and bed
• Move furniture away from the bed
• Window protection/safety bars, barricades with pillows or plastic screens
• Remove dangerous objects from the bedroom (consider sharp objects)
• If any weapons are in the home, lock them away safely outside the
bedroom with the key entrusted to another person
• Have bed partner sleep in a different room until the RBD symptoms are
controlled
• Restraint devices (i.e., sleeping bags and ropes, belts, or dog leashes)
attaching patients to their beds
Pitfalls
• Educate families about RBD and safe sleep environment before

symptoms present or cause injury.
• Missed identification of RBD prior to selection of medications
that can exacerbate symptoms.
Learning Points
• Educate every patient with narcolepsy and their families about

RBD.
• Instruct on creating a safe sleep environment.
• Reevaluate patients frequently after initiation of treatment for
improvement, but also development of side effects, such as
RBD, from medication.
Clinical Case 3
Jennie is a 17-year-old Finnish adolescent girl who presents to

your office for evaluation after several events of near syncope.
Jennie is a healthy, typically developing teenager with no signifi-
cant past medical history. The mother endorses that since late
October Jennie has had frequent episodes of what look like she is
about to pass out. She describes that she has frequent episodes
where her legs become weak and buckle and sometimes she
slouches over. The first episode she remembers occurred when she
was unexpectedly called in class to go up to the board and com-
plete a math problem in school. Since, then she has noticed these
episodes coinciding with when she is scared, angry, or laughing.
She has had one episode where she completely fell to the ground
unexpectedly. In addition, her mother is concerned that this is
making her depressed because she is sleeping all of the time.
However, she generally maintains a 9 pm to 6 am schedule to
attend school.
In early October, she was in Europe for school. She received the
influenza vaccine while she was there and started developing these
symptoms soon after.
General medical exam is unremarkable with no evidence of

orthostasis. Jennie receives a diagnosis of likely vasovagal events
and is sent to cardiology for evaluation. In addition, she is also sent
to psychiatry for concerns of depression and to neurology to evalu-
ate for possible seizure.
Six months later after unremarkable evaluations by cardiology
and neurology, she returns to your office and is still having these
episodes frequently. In addition, she has gained 20 lbs and her
sleepiness is affecting her school performance and grades. Mother
endorses snoring now that she has gained weight. She is now
referred to a sleep specialist to evaluate for sleep apnea due to
weight gain, excessive sleepiness, and snoring. The sleep special-
ist orders a polysomnogram and multiple sleep latency, along with
genetic testing for narcolepsy.
Results of Testing
Sleep logs prior to testing consistent with report of sleep time from
9 pm to 6 am and frequent intentional and unintentional napping
throughout the day.
PSG: AHI 0.7, lowest O2 95 %.
There was a reduced sleep latency during the study (2.5 min),
as well as a reduced REM latency of 4 min (SOREMP*). Sleep
efficiency was reduced (77 %).
MSLT: Mean Sleep Latency: 3.5 min, 5 SOREMPs.
HLA-DQB1*06:02 positive.
Discussion
The case demonstrates a clinical scenario that was seen after the
H1N1 pandemic in 2009. The history and clinical findings are diag-
nostic of narcolepsy with cataplexy. It is important to differentiate
delayed sleep phase disorder (DSPD) in this age group since MSLT
findings may falsely lead to a diagnosis of narcolepsy. Delayed
sleep phase disorders (DSPD) and insufficient sleep syndromes can
demonstrate reduced sleep latency as well as sleep onset REM peri-
ods. A careful history, use of a sleep log or actigraphy prior to PSG/
MSLT, and thorough evaluation of the PSG for other primary sleep
disorders, such as sleep apnea, DSPD, insomnia, or periodic limb
movement disorders is critical to accurately diagnosing narcolepsy.
This is especially important in the diagnosis of narcolepsy type 2,
where there is an absence of cataplexy events to help in distinguish-
ing the diagnosis. A clue to DSPD is delayed sleep latency on the
sleep study and reduced sleep latency with possible sleep onset
REM in the first nap trial of her MSLT.
Narcolepsy has been seen associated with Pandemrix vaccina-
tion (an adjuvanted, influenza pandemic vaccine) and also with
infection by influenza virus during the 2009 A (H1N1) influenza
pandemic [18]. The vaccine safety surveillance system detected
this very rare adverse effect that occurred in less than one out of
10,000 vaccine recipients in subjects receiving AS03 adjuvanted A
(H1N1) pandemic vaccine made using the European inactivation/
purification protocol [19]. Individuals with HLA-DQB1*0602
allele(s) are considered to be genetically susceptible. In 2010, there
was a threefold increase in the number of 17–19 years old in Finland
that were affected with narcolepsy with this HLA subtype [20].
The underlying pathophysiology related to the sudden increase in
incidence was not well understood until recently. Melen et al. evalu-
ated for risk of H1N1 virus infection contributing to the sudden
increase in the incidence of childhood narcolepsy observed in Finland
in 2010 and found it to be unlikely [21]. In 2015, Ahmed et al. pro-
vided evidence of the relationship of the Pandemrix vaccine to the
development of narcolepsy [19]. They demonstrated that a signifi-
cant proportion of sera from HLA-DQB1*0602 haplotype-positive
narcoleptic Finnish patients with a history of Pandemrix vaccination
(vaccine-associated narcolepsy) contained antibodies to hypocretin
receptor 2 compared to sera from nonnarcoleptic individuals with
either 2009 A (H1N1) pandemic influenza infection or history of
receiving the Focetria vaccination given in Italy [18]. Influenza vac-
cines containing the A (H1N1) pdm09 virus strain used in the United
States were not associated with an increased risk of narcolepsy [22].
Therefore, Pandremix is no longer available, but other vaccinations
appear to be safe even for genetically susceptible patients. Effect of
the vaccine on patients with an established diagnosis of narcolepsy is
unknown.
Pitfalls
• The H1N1 influenza infection itself is low risk/likelihood to

cause narcolepsy.
• Be cautious to not cause a fear of all vaccines.
• Consider the diagnosis of narcolepsy, if symptoms are sugges-
tive, following any immune provoking setting (i.e., vaccina-
tions, infections).
Learning Points
• Reassure genetically susceptible individuals about the unlikely

risk with vaccines containing H1N1 influenza and encourage
adherence with recommended vaccination schedules.
• Effect of vaccine in patients with already established narco-
lepsy is unknown.
Clinical Case 4
Isabella is a 16-year-old young lady with narcolepsy with cata-

plexy, who presents for follow-up. She is successfully managed
with sodium oxybate. With treatment, she has had significant
improvement in excessive daytime sleepiness, reduction in cata-
plexy, and improved nighttime sleep. In her senior year, she reports
that she is achieving the highest grades since diagnosis.
As a part of all visits with adolescents, the physician asks social
screening questions about drug and alcohol use, sexual activity
and depression and suicidality. Isabella denies any use of drugs,
nicotine or alcohol. She does feel depressed, but denies any
thoughts of hurting herself. However, she has become sexually
active and endorses that she has missed her last month’s menses.
She is not on any contraception and intermittently uses barrier
protection.
Urine HCG—positive.
Discussion
This case highlights a common challenge for most physicians who

care for patients of a reproductive age with narcolepsy. Pregnancy
is less common in adolescent patients, but the same precautions,
education, and anticipation that are used in adult patients should be
exercised in adolescence. Most patients are advised by the treating
clinician not to take narcolepsy medication during pregnancy to
limit any possible risk. If medication is not used during pregnancy,
safety precautions during pregnancy and after delivery are indi-
cated to enhance safety for the mother/fetus and newborn [23].
However, if the benefits of treating outweigh the risks of adverse
effects or fetal medication-induced abnormalities, then some clini-
cians would treat. It is unknown if there are any fetal risks associ-
ated with a conception when the male partner is treated with
sodium oxybate at the time of conception.
Most medications used in treatment for narcolepsy and cata-
plexy have unknown effects on pregnancy or are class C, which
means there is evidence of adverse effects in the fetus in animal
models, but there are no randomized controlled human studies
available (Table 5.4). Therefore, most patients generally prefer to
abstain from medication during pregnancy, but an unexpected preg-
nancy while on medication is not rare. If medications are to be
withdrawn, it should occur slowly, one dose every 4 days, so to
avoid rebound cataplexy or even a status cataplecticus [24]. The
perceived risks of narcolepsy medication during pregnancy to the
mother and fetus, however, are usually overestimated, as the risk of
teratogenic effects from narcolepsy medications in therapeutic
doses is unknown and based on current data may be essentially
nonexistent [25, 26]. Anti-cataplectic medications can be continued
in pregnancy and some patients may need cesarean sections during
delivery because of cataplexy preventing progression of labor [26].
Pyschosocial screening questions are directed questions about
home life, social activities and friends, school performance, nico-
tine, alcohol and drug use, sexual activity and use of contracep-
tion, as well as depression and suicidality that are a critical part of
every office visit (Table 5.5) [27–29]. When initiating treatment,
psychosocial screening questions can provide the opportunity to
Table 5.4 Pregnancy classification for medications used to treat narcolepsy

Pregnancy
Medication Brand names (Generic) class
Indication: excessive daytime sleepiness
Arousal agent Nuvigil (Armodafinil) C
Provigil (Modafinil) C
Methylphenidate Ritalin C
Ritalin LA C
Ritalin SR C
Metadate CD C
Concerta C
Daytrana C
Quillivant XR C
Dexmethylphenidate Focalin C
Focalin XR C
Amphetamine Adderall (mixed amphetamine salt) C
Adderall XR C
Vyvanse (Lisdexamfetamine) C
Dexedrine (Dextroamphetamine) C
Dexedrine Spansule C
C
Methamphetamine Desoxyn C
Indication: cataplexy
SNRI Effexor (Venlafaxine) C
Effexor XR C
Pristiq (Desvenlafaxine) C
TCA Tofranil (Ipramine) N
Avantyl, Pamelor (Nortriptyline) N
Vivactil (Protrypyline) N
Anafranil (Clomipramine) C
SSRI Prozac (Fluoxetine) C
Zoloft (Sertraline) C
Paxil (Paroxetine) D
Lexapro (Escitalopram) C
Celexa (Citalopram) C
Indication: fragmented sleep
Hypnotics Ambien (Zolpidem) C
Sonata (Zaleplon) C
Lunesta (Eszopiclone) C
Remeron (Mirtazapine) C
(continued)

Pregnancy
Medication Brand names (Generic) class
Indication: cataplexy and EDS
Noradrenergic Strattera (Atomoxetine) C
MAOI N/A for narcolepsy N/A
Type A Eldepryl, Zelapar (Selegiline) C
Type B
Indication: EDS, cataplexy, improved sleep
GABA Xyrem (Sodium oxybate) C
Indication: RBD
Benzodiazepine Klonopin (Clonazepam) D
other Melatonin Unknown
Mirapex (Pramipexole) C
N, not classified
Table 5.5 Psychosocial screening questions

Psychosocial screening
Category Example questions
Home How are things at home?
Who lives at home?
How do you get along with everyone at home?
Education What grade are you in?
Is it a new school?
How are things at school?
What classes do you like best? Least?
Grades?
What do you want to be when you grow up?
Activities What do you do for fun?
Any after school activities?
Do you play sports or exercise?
Who do you do fun things with?
Do you have a best friend?
Who do you hang out with?
Who are your friends?
Who do you go to with problems?
What do you do during nights and weekends?
(continued)

Psychosocial screening
Category Example questions
Drugs/ Do you drink coffee, tea, or caffeinated colas?
alcohol/ Do you smoke cigarettes or ever tried one?
nicotine Have you ever tasted alcohol?
Do any of your friends smoke, drink, or use drugs? What drugs
have you tried?
Have you ever injected drugs or steroids?
Depression How do you feel today on a scale of 0–10, with zero as very
sad and ten as very happy?
Have you ever felt less than five?
What made you feel that way?
Sexual Are you attracted to boys? Girls?
activity Do you have a boyfriend or girlfriend? How long?
Do you get along well?
Do you have sex?
Do you know how to protect yourself from STIs and
pregnancy?
Suicidality Did you ever think about hurting yourself?
Think that life wasn't worth living?
Hope that when you went to sleep you wouldn’t wake up again?
Do you know anyone who has committed suicide?
discuss the importance of more than one form of contraception to

reduce the likelihood of accidental pregnancy and potential expo-
sures to the fetus. Additionally, psychosocial screening questions
provide an introduction to the discussion about the danger of sub-
stance abuse and use independently, but in conjunction with the
substantially greater risk of use or abuse with any of the treatments
for narcolepsy.
Pitfalls
• All medications typically used in the treatment of narcolepsy

and cataplexy are pregnancy class C or have unknown
effects.
• Pregnancy prevention strategies in adolescence are vital to pre-

venting teen pregnancy and possible adverse effects in case of a
pregnancy.
• In general, medication withdrawal should occur slowly to avoid
rebound cataplexy or status cataplecticus.
Learning Points
• Discussion about contraception should occur prior to initiation

of treatment and routinely at all follow-up visits in treated
patients.
• Psychosocial screening questions are an important part of every
appointment to screen for possible teen pregnancy and impact
on the developing fetus.
• Educate patients on all risks and side effects of medication,
including potential effects on the mother and fetus if a preg-
nancy occurs.
• If a pregnancy occurs and medication is withdrawn, safety pre-
cautions during pregnancy and after delivery are indicated to
enhance safety for the mother/fetus and newborn.
Conclusions
Narcolepsy is a rare condition that is frequently misdiagnosed.

Improved physician understanding of the symptoms of narcolepsy
and cataplexy (Table 5.1) and the type of questions that may be
helpful in identifying these symptoms (Table 5.2) may provide a
shorter time to appropriate diagnosis and initiation of treatment for
patients with narcolepsy. It is especially important for physicians,
such as pediatricians, who treat the adolescent age group to be able
to recognize patients that may fit clinical criteria for the diagnosis.
When initiating treatment, evaluating the patient with psychoso-
cial screening questions can be valuable in reducing medication
associated morbidity and possibly mortality. Discussion about
important psychosocial factors, such contraception and pregnancy,
use of drugs or alcohol and evaluation for depression or suicidality
can be as influential on the quality of life for the patient as the
selection of medication for treatment.
Acknowledgements The authors thank Michael Thorpy, MD for comments

and review of this chapter.
manuscript.
References
1. American Academy of Sleep Medicine. International classification of
sleep disorders. 3rd ed. Darien, IL: American Academy of Sleep Medicine;
2014.
2. Thorpy MJ, Krieger AC. Delayed diagnosis of narcolepsy: characteriza-
tion and impact. Sleep Med. 2014;15(5):502–7.
3. Dauvilliers Y, Montplaisir J, Molinari N, Carlander B, Ondze B, Besset A,
et al. Age at onset of narcolepsy in two large populations of patients in France
and Quebec. Neurology. 2001;57(11):2029–33.
4. Nevsimalova S. Narcolepsy in childhood. Sleep Med Rev. 2009;13(2):
169–80.
5. Serra L, Montagna P, Mignot E, Lugaresi E, Plazzi G. Cataplexy features
in childhood narcolepsy. Mov Disord. 2008;23(6):858–65.
6. Plazzi G, Pizza F, Palaia V, Franceschini C, Poli F, Moghadam KK, et al.
Complex movement disorders at disease onset in childhood narcolepsy
with cataplexy. Brain. 2011;134(Pt 12):3477–89.
7. Honda Y. Clinical features of narcolepsy: Japanese experience. In: Honda
Y, Juji T, editors. HLA in narcolepsy. New York: Springer; 1988. p. 24–57.
8. Anic-Labat S, Guilleminault C, Kraemer HC, Meehan J, Arrigoni J,
Mignot E. Validation of a cataplexy questionnaire in 983 sleep-disorders
patients. Sleep. 1999;22(1):77–87.
9. Guilleminault C, Pelayo R. Narcolepsy in children: a practical guide to its
diagnosis, treatment and follow-up. Paediatr Drug. 2000;2(1):1–9.
10. Macleod S, Ferrie C, Zuberi SM. Symptoms of narcolepsy in children mis-
interpreted as epilepsy. Epileptic Disord. 2005;7(1):13–7.
11. Ingravallo F, Gnucci V, Pizza F, Vignatelli L, Govi A, Dormi A, et al. The
burden of narcolepsy with cataplexy: how disease history and clinical features
influence socio-economic outcomes. Sleep Med. 2012;13(10):1293–300.
12. Rosenberg R, Kim AY. The AWAKEN survey: knowledge of narcolepsy
among physicians and the general population. Postgrad Med. 2014;126(1):
78–86.
13. Nightingale S, Orgill JC, Ebrahim IO, de Lacy SF, Agrawal S, Williams
AJ. The association between narcolepsy and REM behavior disorder
(RBD). Sleep Med. 2005;6(3):253–8.
14. Geisler P, Meier-Ewert K, Matsubayshi K. Rapid eye movements, muscle
twitches and sawtooth waves in the sleep of narcoleptic patients and con-
trols. Electroencephalogr Clin Neurophysiol. 1987;67(6):499–507.
15. Frauscher B, Ehrmann L, Mitterling T, Gabelia D, Gschliesser V,

Brandauer E, et al. Delayed diagnosis, range of severity, and multiple sleep
comorbidities: a clinical and polysomnographic analysis of 100 patients of
the innsbruck narcolepsy cohort. J Clin Sleep Med. 2013;9(8):805–12.
16. Billiard M. REM sleep behavior disorder and narcolepsy. CNS Neurol
Disord Drug Targets. 2009;8(4):264–70.
17. Buskova J, Kemlink D, Ibarburu V, Nevsimalova S, Sonka K.
Antidepressants substantially affect basic REM sleep characteristics in
narcolepsy-cataplexy patients. Neuroendocrinol Lett. 2015;36(5):430–3.
18. Ahmed SS, Volkmuth W, Duca J, Corti L, Pallaoro M, Pezzicoli A, et al.
Antibodies to influenza nucleoprotein cross-react with human hypocretin
receptor 2. Sci Transl Med. 2015;7(294), 294ra105.
19. Ahmed SS, Schur PH, MacDonald NE, Steinman L. Narcolepsy, 2009
A(H1N1) pandemic influenza, and pandemic influenza vaccinations: what
is known and unknown about the neurological disorder, the role for auto-
immunity, and vaccine adjuvants. J Autoimmun. 2014;50:1–11.
20. Partinen M, Saarenpaa-Heikkila O, Ilveskoski I, Hublin C, Linna M,
Olsen P, et al. Increased incidence and clinical picture of childhood narco-
lepsy following the 2009 H1N1 pandemic vaccination campaign in
Finland. PLoS One. 2012;7(3), e33723.
21. Melen K, Partinen M, Tynell J, Sillanpaa M, Himanen SL, Saarenpaa-
Heikkila O, et al. No serological evidence of influenza A H1N1pdm09
virus infection as a contributing factor in childhood narcolepsy after
Pandemrix vaccination campaign in Finland. PLoS One. 2013;8(8),
e68402.
22. Duffy J, Weintraub E, Vellozzi C, DeStefano F. Narcolepsy and influenza
A(H1N1) pandemic 2009 vaccination in the United States. Neurology.
2014;83(20):1823–30.
23. Hoque R, Chesson AL. Conception, pregnancy, delivery, and breastfeeding
in a narcoleptic patient with cataplexy. J Clin Sleep Med. 2008;4(6):601–3.
24. Billiard M. Narcolepsy: current treatment options and future approaches.
Neuropsychiatr Dis Treat. 2008;4(3):557–66.
25. Thorpy MJ. Pregnancy and anesthesia in narcolepsy. In: Thorpy MJ,
Goswami M, Pandi-Perumal SR, editors. Narcolepsy: a clinical guide. 2nd
ed. New York: Springer; 2016. p. 351–6.
26. Thorpy M, Zhao CG, Dauvilliers Y. Management of narcolepsy during
pregnancy. Sleep Med. 2013;14(4):367–76.
27. Gupta M, Mishra C. A comprehensive scoring system for assessing psy-
chosocial risk status of adolescents girls through ‘HEEADSSS’approach.
Indian J Prev Soc Med. 2011;42:241–52.
28. Delisi K, Gold MA. The initial adolescent preventive care visit. Clin
Obstet Gynecol. 2008;51(2):190–204.
29. Duncan P, Frankowski B, Carey P, Kallock E, Delaney T, Dixon R, et al.
Improvement in adolescent screening and counseling rates for risk behav-
iors and developmental tasks. Pediatrics. 2012;130(5):e1345–51.
Parasomnias in Adolescents
6
Joseph Kaleyias, Rebecca Quattrucci Scott,
and Sanjeev V. Kothare
Abbreviations
ADs Arousal disorders

CA Confusional arousals
ICSD-3 International classification of sleep disorders
NES Night eating syndrome
NFLE Nocturnal frontal lobe epilepsy
OSAS Obstructive sleep apnea syndrome
PLMS Periodic limb movements of sleep
J. Kaleyias, M.D., Ph.D.

Department of Paediatrics, Colchester Hospital University NHS
Foundation Trust, Turner Road, Colchester, Essex CO4 5JL, UK
e-mail: kaleyias@hotmail.com;
Joseph.kalegias@colchesterhospital.nhs.uk
R. Quattrucci Scott, Ph.D.
Department of Neurology, NYU Langone Medical Center,
NYU Comprehensive Epilepsy Center-Sleep Center,
New York, NY, USA
e-mail: rebecca.scott@nyumc.org
New York, NY, USA

80 J. Kaleyias et al.
PSG Polysomnography
REM Rapid eye movement
RDB REM behavior disorder
RLS Restless legs syndrome
SRED Sleep-related eating disorder
SSRI Selective serotonin reuptake inhibitor
ST Sleep terrors
SW Sleep-walking
SWS Slow wave sleep
Clinical Case 1
Two brothers aged 13 and 16 years old were brought to the emer-
gency room accompanied by their parents due to a violent incident
which occurred around 3 am in the children’s bedroom. The
younger boy reported that his brother punched him violently in
sleep, pushed him away, and finally attempted to chock him while
screaming loudly. The clinical examination of the younger boy
revealed several bruises and lacerations consistent with his allega-
tions. The elder boy reported that, when his parents woke him up
during that incident, he was dreaming that he was in a space craft
and was fighting with an alien. Several months ago, he began spo-
radically to have episodes in which he would sit up in bed while
sleeping, with his eyes closed, speak loudly and clearly for several
minutes, and then fall back to sleep. Other behaviors included run-
ning out of his room. The frequency of these episodes gradually
increased and in the last month he had at least three episodes every
week. The adolescent was difficult to wake up during these events;
on awakening, he had partial dream recall of a violent scene,
appeared confused, and was unaware of the motor activity. The
adolescent suffers from depression and is under anti-depressant
treatment for the last 9 months. The patient denied smoking or
consuming alcohol. The physical examination was unremarkable.
Overnight polysomnographic monitoring showed a total sleep
time of 8.1 h, poor sleep continuity, decreased sleep efficiency, and
a lack of normal muscle paralysis (atonia) during REM sleep. The
patient was diagnosed as having REM sleep behavior disorder
(RBD). The selective serotonin reuptake inhibitor (SSRI) was
6 Parasomnias in Adolescents 81
withdrawn and his depression was treated with cognitive behavior

therapy only. On follow-up, he reported sleeping well without
abnormal activities.
Discussion
This case illustrates a young adolescent with a recent onset history

of REM behavior disorder that was clearly associated with the use
of anti-depressant medication. REM sleep behavior disorder (RBD)
is a parasomnia characterized by complex motor activity associ-
ated with elaborate dream enactment, which corresponds with the
dream sequence [1–3]. Often, it is injury to self or bed partner that
brings the patient to the attention of the clinician. RDB is accom-
panied with lack of REM atonia [4].
In teenagers, and young children, it has been seen with narco-
lepsy, SSRI use, and certain syndromes like Smith Magenis syn-
drome [5]. In young adult, it may be caused by chronic alcoholism,
brainstem tumors, multiple sclerosis, and SSRI use [6]. In adults
>50 years, it may be a precursor to a parkinsonian syndrome [7]. It
is classically seen in men >50 years of age, with a prevalence of
0.5 %, while the estimated prevalence is 0.38 % in the general popu-
lation [1]. RBD can occur in a chronic as well as an acute form.
Acute forms are associated mainly with withdrawal states from
sedative-hypnotic agents and alcohol [8]. It is important to note that
many SSRIs are known to cause RBD, elevating tonic submental
electromyogram activity during REM sleep [9]. The chronic form
of RBD can be either idiopathic or associated with neurological
disorders, most notably synucleinopathies such as Parkinson’s dis-
ease, multiple system atrophy, and dementia with Lewy body dis-
ease [10]. The most compelling research, conducted by numerous
international investigators, concerns the strong associations of RBD
with these neurodegenerative disorders [7, 11]. RBD can be the first
clinical manifestation of future alpha-synucleinopathy neurodegen-
eration. Treatment includes clonazepam and melatonin [12–15].
Clonazepam has long been suggested as the first-line treatment
option for RBD. However, evidence supporting melatonin therapy
is expanding [13]. Melatonin appears to be beneficial for the man-
agement of RBD with reductions in clinical behavioral outcomes
and decrease in muscle tonicity during REM sleep. Melatonin also

has a favorable safety and tolerability profile over clonazepam
with limited potential for drug–drug interactions, an important
consideration especially in elderly individuals and teenagers with
RBD. Prospective clinical trials are necessary to establish evi-
dence-basis for melatonin and clonazepam as RBD therapies [13].
Until new evidence is made available, the small body of support-
ive literature and favorable adverse effect profile make melatonin
an attractive treatment option for patients with RBD [13].
Pitfalls
• The finding of REM sleep without atonia only on a polysomno-

gram does not establish a diagnosis of RBD. RBD is diagnosed
based on clinical symptoms of disturbing behaviors during
sleep associated with dreaming and violent behavior.
• The complex interactions between RBD, depression, and cog-
nitive impairment sometimes lead to misinterpretation of the
clinical symptoms.
Learning points
• RBD is often overlooked as a diagnosis which is based on the

clinical history and PSG findings.
• RBD often results in injury to the patient, bed partner, or both.
• RBD should be differentiated from nightmares, which can
occur at any age and is usually followed by abrupt awakenings
accompanied by a sensation of fear or panic.
• RBD should be differentiated from sleep terrors and sleepwalk-
ing, which occur during stage III of non-REM sleep, more typi-
cally in the first-half of the night and without clear dream recall.
• RBD may be associated with SSRI antidepressant medications.
Discontinuation of SSRIs, changing to a different SSRI, or
changing to a different class of antidepressant such as bupro-
pion (if feasible) may also be a viable option for some patients.
• RBD is a treatable condition.
Clinical Case 2
A female adolescent 17 years old was brought to the general pae-

diatric outpatient clinic by her parents due to recent onset of obe-
sity. She had experienced depressed mood and sleep disturbance
for 12 months. Parents have become concerned around her sleep
pattern along with a recent increase of her weight, which has
increased by 15 kg during a period of 4 months. Parents had wit-
nessed during the past 6 months several episodes of eating, drink-
ing diverse types of food during nocturnal sleep time, usually
starting in the first hours of sleep. During the episodes she would
remain with the eyes almost closed, usually not speaking sponta-
neously but when asked by the relatives, she could respond inco-
herently. She had complete amnesia or partial recall of these
episodes and was surprised to find the remains of night eating in
her bed the next morning. The episodes were increasing in fre-
quency, occurring 2–3 times per week. Parents reported up to five
episodes every night, with each eating episode lasting 10–20 min.
She also complained of morning nausea, reduction of appetite, and
fatigue. Moreover, the patient has become concerned due to the
urge to move her legs in the late evening while lying in her bed,
reduced by physical movement. Physical and neurological exami-
nations and all laboratory tests including serum ferritin levels at
60 μg/L were normal. The clinical suspicious of sleep-related eat-
ing disorder (SRED) associated with Restless Leg Syndrome
(RLS) was raised. A sleep study confirmed periodic limb move-
ments of sleep (PLMS), often associated with SRED. Pramipexole
was started at 0.125 mg in the evening. The adolescent was reas-
sessed after 4 months and was found to be free of symptoms and
her weight reduced to 57 kg.
Discussion
The ICSD-3 defines sleep-related eating disorder (SRED) as a

NREM sleep parasomnias characterized by recurrent episodes of
involuntary eating occurring after an arousal from the main sleep
period with partial or complete amnesia for the event, resulting in
weight gain from eating high calorie foods and causing various
injuries due to consumption of inedible or toxic items [1]. Level of
consciousness during SRED episodes ranges from partial con-
sciousness to dense unawareness typical of somnambulistic epi-
sodes [16]. This disorder typically involves eating peculiar forms
or combinations of food, or possibly dangerous or toxic sub-
stances. Like disorders of arousal, most patients do not have full
recall of the event. Eating can occur multiple times in one night,
typically with high caloric foods.
SRED can be idiopathic or commonly associated with other
primary sleep disorders such as sleepwalking, restless legs syn-
drome (RLS), obstructive sleep apnea syndrome (OSAS), other
clinical conditions, or use of sedative-hypnotic medications
[16–21].
SRED should be distinguished from night eating syndrome
(NES), which is characterized by full recall of the eating and
absence of bizarre or toxic ingestion [22]. Night eating syndrome
(NES) is another important condition in the disordered night-time
eating spectrum, showing hyperphagia episodes just before noc-
turnal sleep without accompanying amnesia. NES could be con-
sidered an abnormality in the circadian rhythm of meal timing
with accompanying anxiety disorder. The two conditions often
overlap and possibly share a common pathophysiology [16].
The sleep-related eating episodes are not linked to daytime eat-
ing disturbances such as bulimia nervosa, binge-eating disorder, or
anorexia nervosa [1]. The average age of onset is approximately
from 22–27 years. This condition affects females (65 %) more than
males, and 80 % of patients describe a diminished level of con-
sciousness during eating episodes, with a varying degree of amne-
sia for the events [23]. The main feature that distinguishes these
two conditions is the level of awareness during the food intake,
which is not impaired in NES. Furthermore, consumption of at
least 25 % of intake after the evening meal and morning anorexia
are typical features of NES. Studies have suggested that SSRIs
may be an effective treatment of NES, while the anti-seizure medi-
cation topiramate may be an effective SRED treatment [24, 25].
SSRIs can worsen SRED [25].
Pitfalls
• SRED should be distinguished from night eating syndrome

(NES), which is characterized by full recall of the eating and
absence of bizarre or toxic ingestion.
• Clinical history should be assessed thoroughly in order to
exclude other sleep disorders associated with SRED as the
treatment should be accordingly modified.
Learning Points
• SRED can be idiopathic or commonly associated with other

primary sleep disorders.
• Treatment options of SRED depend on the coexistence of other
sleep disorders. Treatment of sleep disorders that cause sleep
fragmentation, such as RLS, PLMS, or OSAS, may be of value
for the treatment of SRED, probably by reducing the number of
arousals from sleep that may trigger nocturnal eating episodes.
• Drug-induced SRED can usually be resolved by discontinuing
the offending medication.
• Several drugs, such as SSRIs, zolpidem, triazolam, olanzapine,
risperidone, and quetiapine, can precipitate or worsen SRED.
• Topiramate and dopaminergics have shown therapeutic benefits
through case reports and small uncontrolled studies.
• Pramipexole is expected to improve RLS associated with SRED.
• Benzodiazepines can be an effective form of treatment given
that SRED is a type of non-REM parasomnia.
• Behavioral/lifestyle factors (i.e., dedicating a sufficient amount
of time to sleep, consistency with sleep/wake schedule) should
be evaluated and addressed given that insufficient sleep and/or
an irregular sleep schedule can trigger parasomnias in those
already predisposed.
Clinical Case 3
A young college student aged 19 years old was prosecuted due to

violent behavior during the previous night. After going to bed at
about 11 pm, he got out of bed between midnight and 1 am and
performed a variety of activities. He went to the female side of the

dormitory walking with his eyes open, but he did not respond to the
calling out of his name. He was displaying violent behavior includ-
ing moaning, shouting, yelling, and thereafter he started kicking
and punching other students, and as a consequence, two of them
were hurt. The patient had no recollection of the episode on waking
up. The young man claimed that he has suffered from sleep walk-
ing since he was a child and that, during the last few weeks, he was
not sleeping well due to anxiety associated with the exams. He
admitted to consumption of alcohol the last few days, but denied
consumption of any illicit drugs. The young man was assessed at
the Sleep Clinic accompanied by his parents who confirmed his
allegation about an underlying sleep disorder. A single overnight
polysomnographic sleep study did not reveal any abnormalities and
the diagnosis of somnambulism was debated. The violent behavior
was attributed to alcohol consumption. Due to medico-legal con-
cerns, the patient was reassessed by another sleep specialist who
requested a two night PSG during which the diagnosis of confu-
sional arousals and somnambulism was documented. Advice
regarding safety issues was given. As the incident was a significant
one, medical treatment was started (clonazepam 0.25 mg/day and
melatonin), with remission of the symptoms.
Discussion
Disorders of arousal (sleep walking, confusional arousal, and sleep

terror) are commonly seen in children, but adults may also experi-
ence such parasomnias [1, 26–29]. All these parasomnias occur most
commonly in the early part of the sleep period and usually in connec-
tion with slow wave sleep. Individuals are usually amnesic or par-
tially amnesic for the event the next day.
NREM parasomnias are classified on the basis of the behaviors
displayed by the patient during the episode [1]. The NREM group
includes confusional arousals, sleep terrors, and sleepwalking and
sleep-related eating disorders. NREM parasomnias typically occur
in childhood, although an onset or persistence into adult life is not
uncommon [1, 26, 28–30]. Their diagnosis is essentially clinical
and often based on patient and bed-partner interviews. ICSD-3 has
revised diagnostic criteria for each of the subtypes above [1, 31].
A typical NREM parasomnia is usually considered a benign con-

dition, easy to recognize and treat. However, the diagnosis of NREM
parasomnia can be challenging when the clinical history is unusual
because of the age of onset, the time or duration of the episodes at
night, the presence of suspected precipitating factors (such as peri-
odic limb movements obstructive respiratory events, insufficient
sleep time, irregular sleep/wake schedule), the unresponsiveness to
conventional therapy, or the occurrence of complex or dangerous
behaviors [1, 32–36]. On occasion, NREM parasomnia can be dan-
gerous, resulting in injurious accidents or, not infrequently, can lead
to sleep disruption [1, 34]. According to the American Academy of
Sleep Medicine (AASM) [1], PSG can provide support for the clini-
cal diagnosis of NREM parasomnia by documenting multiple arous-
als from slow wave sleep (with or without accompanying behaviors
typical of the parasomnia) and is advisable. In fact, NREM para-
somnia was found in a similar proportion of people with childhood
(67 %) or adulthood onset of the disorder (55 %). Therefore, age at
onset should not be considered alone as a determining feature
against the clinical diagnosis [31]. In addition, the PSG helps to rule
out a seizure disorder, a common differential diagnosis [37].
NREM parasomnia episodes can be precipitated by external
and internal factors in predisposed individuals. Any factor that
increases the proportion of SWS (sleep deprivation or substances
use) or sleep fragmentation with frequent arousals can facilitate
events [31].
1. Confusional arousals
Confusional arousals (CA) are characterized by disoriented
behavior or slow mentation during or after an arousal from
NREM sleep [1]. They occur most often out of stage N3 sleep
and during the first third of the night. Therefore, most of the
episodes tend to occur at the same time every night and can be
predictable. The patient often displays vocalizations with occa-
sional complex behaviors and typically has a poor recall of
events the following day. Attempts to awaken the person are
often unsuccessful and may be met with vigorous resistance;
occasionally, the patient can become aggressive and violent.
Prevalence rate in children 3–13 years of age is 17.3 %, while in
children older than 15 years and in adults, prevalence is as high
as 6.9 % [33]. In most cases, patients outgrow the problem.
Clinical diagnosis may be especially challenging when there

are similarities to other paroxysmal nocturnal events such as
REM parasomnia or epilepsy [38–40], in particular in those
patients in whom multiple conditions coexist [37, 41, 42]. The
differential diagnosis of NFLE from Nocturnal temporal lobe
epilepsy (NTLE) and NREM sleep parasomnias is a challeng-
ing issue [43]. Frontal lobe seizures are more likely to occur
during sleep than temporal lobe seizures. They may show
bizarre semiology with posturing, ambulation, violent out-
bursts, and complex behaviors. Often, NFLE is misdiagnosed
as sleep apnea due to prominent choking or motor activity [44].
Only a third show clear epileptiform abnormalities on routine
EEG and only 50 % show clear ictal electrographic correlate.
The validated Frontal Lobe Epilepsy Parasomnias (FLEP)
scale, developed by Derry et al. [45, 46], has been particularly
useful in distinguishing NFLE from NREM sleep parasomnias.
Table 6.1 shows features which can be used in the positive iden-
tification of parasomnias [46].
2. Night terrors
Sleep terrors (ST), also known as night terrors or pavor noc-
turnus, are conditions characterized by a sudden and unexpected
arousal from stage N3, with an abrupt scream and behavioral
manifestations of intense fear. They are associated with intense
autonomic and motor symptoms, such as crying or screaming.
These events can be dramatic and disturbing to the family, yet
the patient may be unfazed by the events. The child cannot be
consoled or woken and typically has a partial or complete amne-
sia of the episodes the next day [1, 47]. Prevalence of ST varies
with age from 6.5 % in children to 1 % in the elderly [31].
3. Sleepwalking
Sleepwalking (SW) is an arousal disorder culminating in
walking around in an altered state with impaired judgment.
Sleepwalking occurs most often out of stage N3 sleep and dur-
ing the first third of the night. SW is an expression of simultane-
ously activated states of (partial) sleep and (partial) wakefulness,
a complex dissociated state, with clinical consequences [48].
Prevalence in childhood is as high as 17 %, with a peak age
at 12 years. Sleepwalking typically decreases in frequency
until adulthood, but 3 % of adults continue to sleepwalk [49].
6
Table 6.1 Features for the differential diagnosis between parasomnias and nocturnal frontal lobe epilepsy (NFLE)
Do not discriminate between
Features Strongly favoring parasomnias Moderately favoring parasomnias parasomnias and NFLE
External (noise) or internal +
(cough, snore) trigger
Duration of the event >2 min Brevity
Pattern Waxing/waning Variability/absence of stereotypy
Behavior Sobbing Semi-purposeful, fumbling, Fearful emotional
Sad emotional manipulation of nearby objects
Parasomnias in Adolescents
Manifestations Yawning Coughing

Scratching
Prominent nose-rubbing
Motor activity Rolling over the bed Tremor/trembling Sitting
Myoclonic jerks Standing/walking
Physical and verbal interaction +
Offset of event Failure to fully arouse after event
even with complex behavior
Indistinct offset
Recorded events during PSG Discordance between severity No events recoding during the 1st night Brief arousals (up to 10 s)
and duration of reported event Few events recorded in total (<3) without definite semiological
and recorded event features of epilepsy
89
SW needs to be differentiated from nocturnal seizures. Safety

and legal implications have to be addressed. It is important to
make the bedroom as safe as possible to minimize the risk of
injury, by sleeping on the ground floor, removing obstructions
in the bedroom, and closing doors and windows [50].
Sometimes, SW can become crippling because of its frequency
(several times a week or a night), because of the risks associ-
ated with the behavior (going outside, manipulating sharp
objects, etc.), or violence (throwing objects, using weapons,
etc.) or because of its consequences on everyday quality of life
(sleepiness, fatigue, insomnia, anxiety, and depressive symp-
toms). In these situations, treatment is required (Fig. 6.1). These
include sleep hygiene, securing the environment for safety,
reduction of alcohol consumption, and treatments of precipitat-
ing factors like OSA, PLMS, or anxiety that could exacerbate
episodes. No large controlled trials of drugs have been con-
ducted in SW. Tricyclic antidepressants or benzodiazepines can
be used as good treatment options. If pharmacological
approaches are warranted, regular follow-up is recommended
Sleep walking
Risk assessment
(frequency, violence, consequences)
NO
DisablingSW YES
Safety precautions
Sleep hygiene
No treatment Avoid alcohol PSG
Reassure family Avoid medication inducing SW
Confirmation coexistent sleep disorders Differential

of SW diagnosis (OSAS, PLMS) diagnosis
RBD
NFLE
Treatment Treat the sleep
disorder facilitating
SW
Pharmaceutical Non-pharmaceutical
(clonazepam) Cognitive Behavioural
Therapy
Fig. 6.1 Diagnostic approach and treatment options for sleepwalking. SW

sleepwalking, PSG polysomnography, OSAS obstructive sleep apnea syndrome,
RDB REM sleep behavior disorder, NFLE nocturnal frontal lobe epilepsy
to determine continued need for management and then to safely

taper or discontinue the medication in a manner that will not
result in withdrawal.
Psychotherapy may also be initiated to improve anxiety and
sometimes insomnia [51].
Pitfalls
• Neither RBD, nor arousal disorders (ADs) may manifest during

a single overnight polysomnographic (PSG) study in the sleep
laboratory.
• The role of alcohol is controversial. It is questionable whether
an individual who is heavily intoxicated claims to have been
sleepwalking.
Learning Points
• All patients with disabling frequent SW should have a poly-

somnography in order to confirm the sudden awakenings from
slow-wave sleep with abnormal behaviors and exclude differen-
tial diagnosis such as nocturnal epilepsy or REM sleep behav-
ior disorder.
• Disorders of arousal associated with violence should always be
investigated and adequately treated. Full neuropsychological or
psychiatric assessment may be necessary, especially if there is
a medico-legal issue at stake.
• All factors inducing an increase of slow-wave sleep and sleep
fragmentation can thus increase the frequency of the episodes.
Patients should be encouraged to have regular sleep schedules
and to avoid sleep deprivation.
Sleepwalkers report a clear association between the occurrence

and the severity of sleepwalking episodes and their alcohol
consumption.

No off-label use of drugs or products has been discussed in the manuscript.
References
1. American Sleep Disorders Association. International classification of
sleep disorders, Third Edition (ICSD-3) Revised: Diagnostic and Coding
Manual. Rochester, MN: American Sleep Disorders Association; 2014.
2. Mahowald MW, Schenck CH. The REM sleep behavior disorder odyssey.
Sleep Med Rev. 2009;13(6):381–4.
3. Schenck CH. Rapid eye movement sleep behavior disorder: current
knowledge and future directions. Sleep Med. 2013;14(8):699–702.
4. Budhiraja R. The man who fought in sleep. J Clin Sleep Med.
2007;3(4):427–8.
5. Kolla BP, Mansukhani MP. Antidepressants trigger an early clinical pre-
sentation of REM sleep behavior disorder: the jury is still out. Sleep.
2014;37(8):1393.
6. Postuma RB, Gagnon JF, Tuineaig M, et al. Antidepressants and REM
sleep behavior disorder: isolated side effect or neurodegenerative signal?
Sleep. 2013;36(11):1579–85.
7. Boeve BF. REM sleep behavior disorder: updated review of the core fea-
tures, the REM sleep behavior disorder- neurodegenerative disease asso-
ciation, evolving concepts, controversies, and future directions. Ann N Y
Acad Sci. 2010;1184:15–54.
8. Parish JM. Violent dreaming and antidepressant drugs: or how paroxetine
made me dream that I was fighting Saddam Hussein. J Clin Sleep Med.
2007;3(5):529–31.
9. Winkelman JM, James L. Serotonergic antidepressants are associated with
REM sleep without atonia. Sleep. 2004;27(2):317–21.
10. Boeve BF, Silber MH, Parisi JE, et al. Synucleinopathy pathology and
REM sleep behavior disorder plus dementia or parkinsonism. Neurology.
2003;61(1):40–5.
11. Schenck CH, Boeve BF. The strong presence of REM sleep behavior dis-
order in PD: clinical and research implications. Neurology. 2011;77(11):
1030–2.
12. Schenck CH. The far side of sleep: Towards a deeper understanding of
parasomnias and nocturnal seizures. Sleep Sci. 2014;7(3):129–34.
13. McGrane IR, Leung JG, St Louis EK, Boeve BF. Melatonin therapy for
REM sleep behavior disorder: a critical review of evidence. Sleep Med.
2015;16(1):19–26.
14. Aurora RN, Zak RS, Maganti RK, et al. Best practice guide for the treat-
ment of REM sleep behavior disorder (RBD). J Clin Sleep Med.
2010;6:85–90.
15. McCarter SJ, Boswell CL, St Louis EK, et al. Treatment outcomes in REM
sleep behavior disorder. Sleep Med. 2013;14(3):237–42.
16. Inoue Y. Sleep-related eating disorder and its associated conditions.
Psychiatry Clin Neurosci. 2015;69(6):309–20.
17. Lu ML, Shen WW. Sleep-related eating disorder induced by risperidone.
J Clin Psychiatry. 2004;65(2):272–4.
18. Yun CH, Ji KH. Zolpidem-induced sleep-related eating disorder. J Neurol

Sci. 2010;288(1–2):385–6.
19. Ulman TF, Von Holle AV, Torgersen L, Stoltenberg C, Reichborn-
Kjennerud T, Bulik CM. Sleep disturbances and binge eating disorder
symptoms during and after pregnancy. Sleep. 2012;35(10):1403–11.
20. Provini F, Antelmi E, Vignatelli L, Zaniboni A, Naldi G, Calandra-
Buonaura G, et al. Association of restless legs syndrome with nocturnal
eating: a case–control study. Mov Disord. 2009;24(6):871–7.
21. Antelmi E, Vinai P, Pizza F, Marcatelli M, Speciale M, Provini F. Nocturnal
eating is part of the clinical spectrum of restless legs syndrome and an
underestimated risk factor for increased body mass index. Sleep Med.
2014;15(2):168–72.
22. Howell MJ, Schenck CH, Crow SJ. A review of nighttime eating disor-
ders. Sleep Med Rev. 2009;13(1):23–34.
23. Winkelman JW. Clinical and polysomnographic features of sleep-related
eating disorder. J Clin Psychiatry. 1998;59(1):14–9.
24. Winkelman JW. Efficacy and tolerability if open-lable topiramate in the
treatment of sleep-related eating disorder: a retrospective case series.
J Clin Psychiatry. 2006;67(11):1729–34.
25. Chiaro G, Caletti MT, Provini F. Treatment of sleep-related eating disor-
der. Curr Treat Options Neurol. 2015;17(8):361.
26. Laberge L, Tremblay RE, Vitaro F, Montplaisir J. Development of
parasomnias from childhood to early adolescence. Pediatrics. 2000;106
(1 Pt 1):67–74.
27. Hansakunachai T, Ruangdaraganon N, Udomsubpayakul U, Sombuntham
T, Kotchabhakdi N. Epidemiology of enuresis among school-age children
in Thailand. J Dev Behav Pediatr. 2005;26(5):356–60.
28. Bjorvatn B, Grønli J, Pallesen S. Prevalence of different parasomnias in
the general population. Sleep Med. 2010;11(10):1031–4.
29. Ohayon MM, Guilleminault C, Priest RG. Night terrors, sleepwalking,
and confusional arousals in the general population: their frequency and
relationship to other sleep and mental disorders. J Clin Psychiatry.
1999;60(4):268–76.
30. Ohayon MM, Mahowald MW, Dauvilliers Y, Krystal AD, Leger
D. Prevalence and comorbidity of nocturnal wandering in the US adult
general population. Neurology. 2012;78(20):1583–9.
31. Fois C, Wright MA, Sechi G, Walker MC, Eriksson SH. The utility of poly-
somnography for the diagnosis of NREM parasomnias: an observational
study over 4 years of clinical practice. J Neurol. 2015;262(2):385–93.
32. Provini F, Tinuper P, Bisulli F, Lugaresi E. Arousal disorders. Sleep Med.
2011;12 Suppl 2:S22–6.
33. Mason 2nd TB, Pack AI. Pediatric parasomnias. Sleep. 2007;30(2):141–51.
34. Zadra A, Desautels A, Petit D, Montplaisir J. Somnambulism: clinical aspects
and pathophysiological hypotheses. Lancet Neurol. 2013;12(3):285–94.
35. Chesson Jr AL, Ferber RA, Fry JM, Grigg-Damberger M, Hartse KM,
Hurwitz TD, et al. Practice parameters for the indications for polysomnog-
raphy and related procedures. Sleep. 1997;20(6):406–22.
36. Kushida CA, Littner MR, Morgenthaler T, Alessi CA, Bailey D, Coleman
J, et al. Practice parameters for the indications for polysomnography and
related procedures: an update for 2005. Sleep. 2005;28(4):499–521.
37. Kothare SV, Kaleyias J. Sleep and epilepsy in children and adolescents.
Sleep Med. 2010;11(7):674–85.
38. Bisulli F, Vignatelli L, Provini F, Leta C, Lugaresi E, Tinuper
P. Parasomnias and nocturnal frontal lobe epilepsy (NFLE): lights and
shadows–controversial points in the differential diagnosis. Sleep Med.
2011;12 Suppl 2:27–32.
39. Derry CP, Duncan JS, Berkovic SF. Paroxysmal motor disorders of sleep:
the clinical spectrum and differentiation from epilepsy. Epilepsia.
2006;47(11):1775–91.
40. Zucconi M, Oldani A, Ferini-Strambi L, Bizzozero D, Smirne S. Nocturnal
paroxysmal arousals with motor behaviours during sleep: frontal lobe epi-
lepsy or parasomnia? J Clin Neurophysiol. 1997;14(6):513–22.
41. Manni R, Terzaghi M. Comorbidity between epilepsy and sleep disorders.
Epilepsy Res. 2010;90(3):171–7.
42. Pincherle A, Proserpio P, Didato G, Freri E, Dyljgeri S, Granata T, Nobili
L, Spreafico R, Villani F, et al. Epilepsy and NREM parasomnia: a com-
plex and reciprocal relationship. Sleep Med. 2012;13(4):442–4.
43. Malow BA, Selwa LM, Ross D, Aldrich MS. Lateralizing value of interic-
tal spikes on overnight sleep-EEG studies in temporal lobe epilepsy.
Epilepsia. 1999;40(11):1587–92.
44. Furet O, Goodwin JL, Quan SF. Incidence and remission of parasomnias
among adolescent children in the Tucson Children's Assessment of Sleep
Apnea (TuCASA) study. Southwest J Pulm Crit Care. 2011;2:93–101.
45. Derry CP, Davey M, Johns M, Kron K, Glencross D, Marini C, et al.
Distinguishing sleep disorders from seizures: diagnosing bumps in the
night. Arch Neurol. 2006;63(5):705–10.
46. Derry CP, Harvey AS, Walker MC, Duncan JS, Berkovic SF. NREM
arousal parasomnias and their distinction from nocturnal frontal lobe epi-
lepsy: a video EEG analysis. Sleep. 2009;32(12):1637–44.
47. Nguyen BH, Pérusse D, Paquet J, Petit D, Boivin M, Tremblay RE, et al.
Sleep terrors in children: a prospective study of twins. Pediatrics.
2008;122(6):e1164–7.
48. Pressman MR. Disorders of arousal from sleep and violent behavior: the
role of physical contact and proximity. Sleep. 2007;30(8):1039–47.
49. Goodwin JL, Kaemingk KL, Fregosi RF, Rosen GM, Morgan WJ, Smith
T, et al. Parasomnias and sleep disordered breathing in Caucasian and
Hispanic children—the Tucson Children's Assessment of Sleep Apnea
study. BMC Med. 2004;2:14.
50. Attarian H. Treatment options for parasomnias. Neurol Clin. 2010;28(4):
1089–106.
51. De Cock V. C. Sleepwalking. Curr Treat Options Neurol. 2016;18(2):6.
Sleep in Adolescents
with Psychiatric Disorders 7
Ujjwal Ramtekkar and Anna Ivanenko
Clinical Case: Depression
John is a 16-year-old boy who presents with primary concern of

“feeling tired all the time” to the primary care clinic. He described
feeling tired and unmotivated, but very frustrated since he is unable
to fall asleep on laying down during the day or at night. He reports
“staring at the ceiling” for prolonged time before he falls asleep at
night and complains of not feeling refreshed in the morning. John
stated that the onset of poor sleep was insidious, but he has noticed
it for about 4 weeks and it has gradually worsened over time. He
does report good sleep hygiene at baseline and no major changes
since the onset of sleep issues. John and his parents denied any
history of parasomnias, snoring, drooling, cataplexy, hypnagogic,
or hypnopompic hallucinations. John appears somewhat sullen,
intermittently irritable, and gives very short answers to the
U. Ramtekkar, M.D., M.P.E., M.B.A. (*)

Division of Psychiatry, Compass Health Network, St. Louis,
Wentzville, MO 63385, USA
e-mail: uramtekkar@pbhc.org; drujjal@yahoo.com
A. Ivanenko, M.D., Ph.D.
Department of Psychiatry and Behavioral Sciences, Feinberg School
of Medicine, Northwestern University, Division of Child
and Adolescent Psychiatry, Ann and Robert H. Lurie Children’s
Hospital of Chicago, Chicago, IL, USA
e-mail: a-ivanenko@northwestern.edu

96 U. Ramtekkar and A. Ivanenko
questions. Parents are unaware of any significant issues prior to

onset of sleep problems, but express their worries since John has
had decline in his academic performance for the past 2 months and
has been increasingly reclusive, irritable at home as well as with
his friends. Parents report that John is a perfectionist, an excellent
student and athlete with a steady family environment. On explor-
ing in private, John admits to being “touchy,” irritability, having
difficulty in concentration, losing interest in sports or hanging out
with friends, decreased appetite due to lack of desire to eat even
his favorite food, and generally negative outlook towards life. On
specific questions about major triggers, he reports breaking up
with his girlfriend about 3 months ago and later regretting his deci-
sion. However, his efforts to get back together have failed and he
has been feeling worthless and angry all the time.
On review of medical history, he had tonsillectomy at age 7 and
was briefly on inhalers for exercise-induced asthma. No other
medical or surgical history reported. His medical work up includ-
ing physical exam and baseline laboratory tests so far has been
negative.
Management and Clinical Course
Based on the report of mood symptoms during the private inter-

view, John was administered the Patient Health Questionnaire
(PHQ-9). The responses recorded by John resulted in the rating
scores indicating high risk for clinical depression. On brief safety
assessment, John was deemed to be safe without any acute concern
for self-harm or suicide. Office-based labs including urine drug
screen was performed and the results were negative for any illicit
drugs. It was decided to first address the depressive symptoms due
to the temporal link between the onset of his depressive symptoms
followed by sleep disturbance. On detailed discussion with parents
and John, they felt comfortable with starting an SSRI—Fluoxetine
(Prozac), and were referred to a psychiatrist for further manage-
ment. About 4 weeks later, John returned to clinic for follow-up
and reported partial resolution of depressive symptoms with bet-
ter energy, school participation, and engagement in the family.
7 Sleep in Adolescents with Psychiatric Disorders 97
However, he did report continued difficulty in falling asleep and

daytime fatigue mainly on school days due to continued worries
about his break up and how he “let the parents down.” He was
advised to see the psychologist in office for cognitive behavioral
therapy for insomnia. After about 6 weeks of weekly intervention
that included relaxation training and correction of cognitive distor-
tions, he has progressive improvement of his sleep patterns.
Discussion
Sleep disturbance is one of the core symptoms in the diagnostic

criteria of depressive disorders. Insomnia, hypersomnia, fatigue,
and lack of energy are often observed in adolescents with depres-
sion. Contrary to adults, depressed youth often present with irrita-
bility and behavioral dysregulation, instead of pervasive sadness
and can be easily misdiagnosed with other mood disorders.
Adolescent depression is one of the most common psychiatric dis-
orders and is estimated to affect 8 % of adolescents with a life time
prevalence of over 20 % by age 18 due to its relapsing and remit-
ting course [1]. Despite the high prevalence, more than 70 % of
children and adolescents with depression are not diagnosed or
treated, leading to further risk of more severe psychiatric disor-
ders. Due to the significant prevalence of depression, it is impor-
tant to screen patients under age of 18 presenting with sleep
disturbance in presence of irritability and decline in their social
and academic functioning for possible depression as an underlying
primary psychopathology.
In the recent revision of Diagnostic and Statistical Manual—
DSM-5, major depressive disorder diagnostic criteria require five
or more symptoms to be present during the same period of 2 weeks
leading to change in functioning accompanied by alteration of
mood or loss of interest (anhedonia). These symptoms include
insomnia or hypersomnia occurring nearly daily, fatigue, psycho-
motor agitation, difficulty concentrating, weight loss or appetite
changes, decreased interest in activities, feeling worthless, and
thoughts of death [2]. There are several additional specifiers to fur-
ther characterize the subset of depression (Table 7.1).
Table 7.1 Major depressive disorder criteria based on DSM-5

A. Five or more of the following symptoms during the same 2-weeks period
and represent a change from previous functioning where at least one of the
symptoms is depressed mood or loss of interest and interest or pleasure
1. Depressed mood most of the day, almost every day, indicated by
your own subjective report or by the report of others. This mood
might be characterized by sadness, emptiness, or hopelessness
2. Markedly diminished interest or pleasure in all or almost all
activities most of the day nearly every day
3. Significant weight loss when not dieting or weight gain
4. Inability to sleep or oversleeping nearly every day
5. Psychomotor agitation or retardation nearly every day
6. Fatigue or loss of energy nearly every day
7. Feelings of worthlessness or excessive or inappropriate guilt
(which may be delusional) nearly every day
8. Diminished ability to think or concentrate, or indecisiveness, nearly
every day
9. Recurrent thoughts of death (not just fear of dying), recurrent
suicidal ideation without a specific plan, or a suicide attempt or a
specific plan for committing suicide
B. Symptoms cause clinically significant distress or impairment in social,
occupational, or other important areas of functioning
C. The episode is not due to the effects of a substance or to a medical condition
D. The occurrence is not better explained by schizoaffective disorder,
schizophrenia, schizophreniform disorder, delusional disorder, or other
specified and unspecified schizophrenia spectrum and other psychotic
disorders
E. There has never been a manic episode or a hypomanic episode
While the majority of adolescents with major depression often

report sleep complaints when compared with other age groups,
insomnia (74 %) as well as hypersomnia (36 %) are prevalent in
adolescents [3]. However, presence of both hypersomnia and
insomnia is indicative of increased severity of depression [4, 5].
The subset of depressive specifiers and symptoms are also noted to
be related to specific sleep complaints. In depression with melan-
cholic features, there is early morning awakening and worsening
of depression in the morning. In contrast, depression with atypical
features is characterized by hypersomnia. Insomnia is often asso-
ciated with psychomotor agitation, excessive worrying and somatic
complaints, whereas hypersomnia is associated with psychomotor

retardation, low mood, fatigue, reduced appetite, hopelessness,
and helplessness [5].
Several longitudinal studies have established a close relation-
ship between sleep disturbances and depressive illness over time
indicating possible shared neurophysiological pathways in
depression and sleep disorders [6, 7]. While the onset of sleep
complaints as early as age 4 has been considered a predictor of
depression in adolescence [8, 9], a recent longitudinal study has
also demonstrated that symptoms of depression established in
early adolescence are a moderate predictor of difficulty initiating
sleep (DIS) in early adulthood indicating possible bidirectional
relationship in the psychopathology and physiology [10]. On the
similar lines, there have been studies establishing reciprocal rela-
tionship between sleep complaints and depression. For example,
a community-based, prospective cohort study of adolescents
showed that insomnia at baseline increased the risk of developing
MDD by 2–3 fold and the presence of MDD increased the risk of
subsequent insomnia by 2–3 fold [11]. In addition to the pres-
ence of sleep disturbance, the severity also predicts the risk of
depression as demonstrated in a study of Norwegian adolescents
aged 16–18 years, where presence of insomnia increased the risk
of depression by 4–5 fold but those who slept for <6 h had more
than eightfold increase in risk of depression [12].
In addition to functional impairment, severe depression can
result in suicidal ideations, sometimes culminating in suicide
attempt or completed suicide. It is estimated that over 20 % of
depressed teenagers seriously contemplate suicide, whereas com-
pleted suicide is the third leading cause of death for 15–24-year-
olds [13]. Significant sleep disturbances, both insomnia and
hypersomnia, have been noted in youth with suicidal ideations,
suicide attempts, or completing suicide as compared to those with-
out suicidal thoughts [14, 15]. Moreover, the nature, duration, and
severity of sleep disturbance also appear to be an important risk
factor for suicidal thoughts. For example, the change in the sleep
disturbance in the preceding week has been associated with com-
pleted suicide, and having less than 5 h or more than 10 h of sleep
has been significantly correlated with higher risk of suicidality
[16]. A meta-analysis of studies examining relationship between
sleep disturbance and suicidal thoughts concluded that sleep dis-

turbances in general, as well as insomnia and nightmares individu-
ally, appear to represent a risk factor for suicidal thoughts and
behavior [17].
There have been several studies to identify the objective mark-
ers of depression using sleep measures such as polysomnography
and actigraphy in adolescents. However, the results have been vari-
able in the parameters used and inconsistent in the findings. In a
meta-analysis of PSG studies, the only robust correlation was
found for increased sleep latency and decreased intra and inter-
hemispheric coherence on EEG in depressed youth [18]. In a study
aimed to quantify circadian rhythms in rest-activity cycles using
actigraphy, depressed adolescents showed lower activity levels and
damped circadian rhythm when compared to healthy controls.
These findings were not seen in younger age group and were
unique to adolescents [19]. In general, sleep studies are not used
for the diagnostic or treatment purposes in depression.
Diagnosis of depression often requires comprehensive clinical
assessment by trained professionals to assess comorbid mental
health conditions, rule out general medical disorders as well as
medications that may present as depression (Table 7.2). However,
primary care and specialty medical providers caring for adoles-
cents play an important role in identifying the warning signs and
screening for depressive disorders.
There are several rating scales available for screening and mon-
itoring of depression which can be easily administered during rou-
tine clinic visits. One of the widely used depression rating scales
adapted for teenagers is PHQ-9 (Parent Health Questionnaire)
(Table 7.3), which is validated for use in the medical settings for
depression screening and severity monitoring against the gold
standard. Another adaptation, PHQ-2, has also been promising as
a brief screening tool but not for monitoring treatment, and it does
not appear to be as well-validated as the PHQ-9 in teenagers [20,
21]. Other specific rating scales for teenage depression include
Center for Epidemiologic Studies Depression Scale (CES-D) and
Columbia Suicide-Severity rating scale (CSS) that are shown to be
specific, sensitive, and valid in screening and monitoring severity
of depression [22, 23].
Table 7.2 Differential Medical disorders

diagnosis of depression in
• Hypothyroidism
adolescents
• Anemia
• Mononucleosis
• Chronic fatigue syndrome
• Autoimmune diseases
• Seizure disorders
• SLE or collagen vascular disorder
• Infectious mononucleosis
Medication induced
• Corticosteroids
• Contraceptives
• Stimulants
• Isotretinoin
• Beta blockers
Psychiatric disorders
• Adjustment disorder with depressive
features
• Bipolar disorder
• Substance abuse disorder
• Eating disorders
• ADHD—inattentive presentation
Treatment of adolescent depression consists of psychotherapy,

medication management or both depending on the severity of
symptoms. Cognitive behavioral therapy (CBT) has been found to
be more effective in treatment of milder forms of depression as
compared to other therapies. The first-line medications approved
for treating adolescents are Citalopram (Celexa), Fluoxetine
(Prozac), Sertraline (Zoloft), and Escitalopram (Lexapro).
However, the results from two large, multi-center, randomized
controlled trials—The Treatment for Adolescents with Depression
Study (TADS) and the Treatment of Resistant Depression in
Adolescents (TORDIA), indicate that the most therapeutic
response was found with the combination of cognitive behav-
ioral therapy and SSRI [24, 25]. Interestingly, the presence of
sleep complaints has been associated with responsiveness of
Table 7.3 PHQ-9 modified for teenagers
102
PHQ-9: Modified for teens

Name: ____________Clinician: ___________Date: ___________
Instructions: How often have you been bothered by each of the following symptoms during the past two weeks? For each
symptom put an “X” in the box beneath the answer that best describes how you have been feeling
(0) (1) (2) (3)
Not At All
Several Days
Nearly Every Day
More Than Half the Days
1. Feeling down, depressed, irritable, or hopeless?

2. Little interest or pleasure in doing things?
3. Trouble falling asleep, staying asleep, or sleeping too much?
4. Poor appetite, weight loss, or overeating?
5. Feeling tired, or having little energy?
6. Feeling bad about yourself—or feeling that you are a failure, or that you have let yourself or your family down?
7. Trouble concentrating on things like school work, reading, or watching TV?
8. Moving or speaking so slowly that other people could have noticed?
U. Ramtekkar and A. Ivanenko
7
Or the opposite—being so fidgety or restless that you were moving around a lot more than usual?
9. Thoughts that you would be better off dead, or of hurting yourself in some way?
In the past year have you felt depressed or sad most days, even if you felt okay sometimes?
[ ] Yes [ ] No
If you are experiencing any of the problems on this form, how difficult have these problems made it for you to do your work, take
care of things at home or get along with other people?
[ ] Not difficult at all [ ] Somewhat difficult [ ] Very difficult [ ] Extremely difficult
Has there been a time in the past month when you have had serious thoughts about ending your life?
[ ] Yes [ ] No
Have you EVER, in your WHOLE LIFE, tried to kill yourself or made a suicide attempt?
[ ] Yes [ ] No
Sleep in Adolescents with Psychiatric Disorders
103
depression-focused treatment as well as future relapse of depres-

sion. The TADS study results indicated that sleep issues were the
most common residual symptoms in adolescents under treatment.
Similarly, a longitudinal study of depressed adolescents treated
with different modalities indicated that persistent sleep distur-
bances were associated with poor treatment response independent
of treatment modality, age, and gender [26]. In addition to the
effect of sleep on treatment response of depression, there is also
evidence of the impact of SSRIs on sleep architecture, although
the findings have been inconsistent in various studies depending
on the medication, age, and psychiatric conditions [27]. Although
trazodone has been used in adults and children, co-treatment with
trazodone and SSRI in adolescent has not been more effective in
relieving insomnia [28]. Since there is scarcity of data about use,
effectiveness and safety of sleep adjunctive medications in adoles-
cents, it is important to consider medication properties, sleep
symptoms, and concurrent SSRIs when using sleep medications in
adolescents treated for depression.
In addition to traditional treatment of depression, specific psy-
chotherapy and behavioral interventions to address insomnia can
be used in the treatment of depressed adolescents. CBT for
Insomnia (CBT-i) is a specific modality for insomnia that includes
multiple interventions including sleep diary, sleep hygiene, stimu-
lus control, sleep restriction, and cognitive therapy. In adults with
insomnia and depression, CBT-i has been shown to improve mood
as well as sleep [29]. The application of CBT-i interventions in
depressed adolescents can be effective and may result in better
response to concurrent pharmacological treatment.
Clinical Pearls and Pitfalls: Depression
• Subjective sleep complaints including sleep onset and mainte-

nance insomnia and excessive daytime sleepiness are extremely
common in adolescents with major depressive disorder.
• Early recognition and treatment of sleep disturbance in youth
with major depression significantly improves their health out-
comes and reduces risk for relapse.
Learning Points
• Insomnia and hypersomnia are a major part of the current

DSM-5 diagnostic criteria for major depression.
• Sleep evaluation is an essential part of the assessment of ado-
lescents that present with symptoms of depressive disorders.
• Increased sleep onset latency emerged as a most consistent fea-
ture of insomnia associated with depression in youth.
• Several studies indicated a relationship between sleep distur-
bances and increased risk for suicide among adolescents with
depression.
• Successful treatment of sleep disturbances improves mental
health outcome and reduce risk for relapse in adolescents with
depression.
Clinical Case: PTSD
Jane is a 17-year-old girl senior class student who presents due to

concerns of feeling tired “all the time,” excessive daytime sleepi-
ness, and poor attention. Parents also report that she has been irri-
table, at times “lost in her own world,” and has been avoiding the
tennis practice despite getting selected to play at the state level.
Parents report that Jane has been insisting on quitting sports due
to “tiredness,” despite high chances of being awarded a sports
scholarship at the college of her choice. She is able to attend
school, but her academic grades have declined in the past quarter.
She has not had any history of ADHD, although she was evaluated
due to concerns of inattention, impulsivity, and agitation at age
14. At that time, the symptoms were attributed to exhaustion from
the busy schedule of tennis practice and traveling for tennis camps
in different cities. Jane and her parents denied any medical issues
except for a minor ankle sprain. She does not take any medica-
tions or OTC products. There is a family history of anxiety and
obstructive sleep apnea. On exploring sleep symptoms, she reports
having difficulty falling asleep, nonrestorative sleep despite >9 h
in bed, and feeling exhausted throughout the day. She denied any
OSA-like symptoms. On further questioning, she does report
nightmares on a daily basis with multiple awakenings. When
asked about the content, she reveals that she was sexually assaulted
by two boys at age 14 during the out of town tennis camp that she
disclosed only to close friends in the camp. However, during the
most recent tournament, she saw one of the boys and suddenly
started having anxiety, nightmares about the assault, and irritabil-
ity during the day due to intrusive thoughts. She reports feeling
emotionally drained and very guilty when thinking about the inci-
dent and always worries about the reaction of her parents and
friends if they were to find out. Jane reports that her decision to
quit sports is based on avoiding any chances to confront the boy
again. She also endorses significant anxiety interfering with her
ability to focus on school and family.
Management and Clinical Course
Jane’s parents were involved after she was encouraged to inform

them about the traumatic incident. Jane was referred to the clinic
psychologist who conducted a detailed clinical evaluation includ-
ing an interview of Jane and her parents. Jane was diagnosed with
PTSD and a specific from of psychotherapy—trauma-focused
cognitive behavioral therapy was suggested. Despite some
improvement in her symptoms of PTSD, she continued to report
insomnia and nightmares. She was initiated on low-dose Zoloft
and also suggested to implement relaxation exercises prior to bed-
time. Jane responded well to the combination of therapy and treat-
ment with improvement in anxiety and sleep. Parents also took
action by contacting the appropriate authorities and the tennis
camp organizers.
Discussion
Posttraumatic stress disorder (PTSD) is characterized by the direct

or indirect exposure to the traumatic event, persistent re-experienc-
ing of the event, avoidance of distressing trauma-related stimuli,
negative mood, hyper-arousal and increased reactivity to stimuli,
and at times dissociative symptoms lasting more than a month
(Table 7.4) [2]. According to the recent National Comorbidity
Survey Replication (NCSR), over 5 % adolescents meet criteria for

Posttraumatic stress disorder (PTSD) with higher prevalence in
girls (8 %) than boys (2.3 %) [30]. The increase in prevalence can
be attributed to the variety of traumatic life-threatening events in
the past few decades such as mass shootings, violent crimes, sui-
cide bombings, terrorist attacks, motor vehicle accidents, wars, in
addition to the natural disasters such as hurricanes, earthquakes,
floods, and fire. However, the major causes of traumatic experience
Table 7.4 DSM—5 criteria for PTSD

A. Exposure to actual or threatened death, serious injury, or sexual violence,
in one or more of the following ways:
1. Directly experiencing the traumatic event
2. Witnessing, in person, the event(s) as it occurred to others
3. Learning that the traumatic event(s) occurred to a close family member
or close friend. If the event involved actual or threatened death, it must
have been violent or accidental
4. Experiencing repeated or extreme exposure to aversive details of the
traumatic event(s), (e.g., first responders, collecting body parts; police
officers repeatedly exposed to details of child abuse). This does not
include indirect non-professional exposure through electronic media,
television, movies, or pictures
B. Presence of one (or more) of the following intrusion symptoms associated
with the traumatic event(s), beginning after the traumatic event(s) occurred
1. Recurrent, involuntary, and intrusive distressing memories of the
traumatic events(s)
2. Recurrent distressing dreams in which the content and/or the affect of
the dream is related to the traumatic event
3. Dissociative reactions (e.g., flashbacks) in which individual dream or
act as if the traumatic event(s) were recurring. (Such reactions may
occur on a continuum from brief episodes to complete loss of
awareness of present surroundings)
4. Intense or prolonged distress at exposure to internal or external cues
that symbolize or resemble an aspect of traumatic event
5. Marked physiologic reactions to internal or external cues that
symbolize or resemble an aspect of traumatic event
C. Persistent avoidance of stimuli associated with the traumatic event(s),
beginning after the traumatic event(s) occurred, as evidenced by one or
both of the following:
1. Avoidance of or efforts to avoid distressing memories, thoughts, or
feelings about or closely associated with the traumatic event(s)
(continued)

2. Avoidance of or efforts to avoid external reminders (people, places,
conversations, activities, objects, situations) that arouse distressing
memories, thoughts, or feelings about or closely associated with the
traumatic event(s)
D. Negative alterations in cognitions and mood that began or worsened after
the traumatic event as evidenced by two or more of the following:
1. Inability to remember important aspect of the traumatic event (usually
due to dissociative amnesia; not due to head injury, alcohol, or drugs)
2. Persistent and exaggerated negative beliefs and expectations about
oneself, others or the world (e.g., “I am bad,” “No one can be trusted,”
“The world is completely dangerous”)
3. Persistent, distorted cognitions about the cause and consequences of
traumatic event leading to individual blaming himself/herself or others
4. Persistent, negative, emotional state (e.g., fear, horror, anger, guilt, or
shame)
5. Markedly diminished interest or participation in significant activities
6. Feelings of detachment or estrangement from others
7. Constricted affect: persistent inability to experience positive emotions
E. Marked alterations in arousal and reactivity associated with the traumatic
event(s) as evidence by two (or more) of the following:
1. Irritable behavior and angry outbursts with little or no provocation.
2. Reckless or self-destructive behavior
3. Hypervigilance
4. Exaggerated startle response
5. Problems with concentration
6. Sleep disturbance (difficulty falling or staying asleep or restless sleep)
F. Duration of disturbance (Criteria B, C, D, and E) for more than 1 month
G. Disturbance causes clinically significant distress or impairment in social,
occupational, or other areas of functioning
H. Disturbance is not attributable to the physiological effects of a substance
or another medical condition
in adolescents remain physical abuse, sexual abuse, and witnessing

community violence [31]. Adolescents are more likely than younger
children or adults to exhibit impulsive and aggressive behaviors.
They are also likely to exhibit traumatic re-enactment, in which
they incorporate aspects of the trauma into their daily lives.
Sleep-related symptoms such as recurrent distressing dreams
related to the content of traumatic events and marked alterations in
arousal due to persistent sleep disturbance are the sleep-specific

diagnostic features for PTSD indicating the importance of sleep in
defining the disorder. Over 70 % of individuals in the general popu-
lation diagnosed with PTSD indicate sleep-related symptoms
mainly in the form of initial and intermittent insomnia and night-
mares [32]. In general, adolescents are more likely to exhibit adult-
like PTSD symptoms such as intrusive thoughts and nightmares;
avoidance of discussion of the traumatic event and places or people
psychologically associated with the event; amnesia for an important
aspect of the trauma; withdrawal from friends or usual activities;
detachment from others and hyper arousal, such as sleep difficul-
ties, hyper vigilance, and increased startle response. Adolescents
with chronic PTSD may present with predominantly dissociative
features, including derealization, depersonalization, self-injurious
behavior, substance abuse, and intermittent angry or aggressive out-
bursts. Overall, acute trauma results in hyperarousal states with
insomnia and nightmares; chronic effects of trauma at an early age
can present as dissociation, irritability, and increased sleep [33].
Despite experiencing traumatic events, not everyone develops
PTSD. While sleep problems are part of PTSD phenomenology,
the presence of sleep disturbance and nightmares are also predic-
tive of development of PTSD in the future. In community-based
studies investigating the aftermath of hurricanes, it was reported
that presence of nightmares had a strong correlation with develop-
ment of PTSD in the future and the persistence of sleep problems
predicted the maintenance as well emergence of PTSD symptoms
[34, 35]. Similarly, trauma in childhood can continue to affect
sleep parameters at later ages in adolescence and adulthood in the
form of increased sleep onset latency, lower sleep efficiency, and
increased nocturnal activity [36]. Careful consideration should be
given to comorbid psychiatric disorders during assessment of ado-
lescent PTSD due its effect on treatment outcomes (Table 7.5).
Population-based studies have shown that youth with PTSD have
high risk of anxiety and affective disorders, externalizing disorders
such as ADHD, and oppositional defiant disorder [33, 37]. Of
these, anxiety disorders are the most common comorbid disorder.
Interestingly, in contrast to depressed youth, anxious children and
adolescents are often noted to under-report the sleep problems
despite objective sleep findings and parent report of sleep
Table 7.5 Differential diagnosis of adolescent PTSD

Psychiatric disorders
• Anxiety disorder
• Obsessive compulsive disorder
• Dissociative disorders
• Conversion disorder (functional neurological symptom disorder)
• Schizophrenia
• Mood disorder with psychotic features
• Substance use disorders
Medical disorders
• Traumatic brain injury
• Delirium
• Medication reactions
• Psychosis due to general medical conditions
disruption [38–40]. The number of sleep-related problems is also

positively correlated with severity of the anxiety disorder and
functional impairment [41]. The early onset of sleep problems
may also have predictive value with anxiety [42], as evidenced by
the longitudinal, community-based studies that have demonstrated
that persistent sleep problems as early as at age 5 are a unique
predictor for the development of anxiety disorders, but not depres-
sion during adolescence and adulthood [8, 43].
Diagnosis of adolescent PTSD is largely clinical, based on the
data collected from adolescent and parent interview. The Primary
Care PTSD Screen (PC-PTSD) (Table 7.6) is often used for screen-
ing of PTSD in primary care and other medical settings [44]. In
adolescents, general rating scales such as Child behavior checklist
and self-report rating scales specific for PTSD symptomatology
such as UCLA PTSD reaction index and PTSD symptom scale can
be reliably used to identify and assess the severity of PTSD [45,
46]. Since there is high risk of comorbid psychiatric disorders such
as depression, ADHD, substance abuse in adolescents with PTSD,
it is advised to screen those using disorders using standard screen-
ing instruments such as PHQ-9, Vanderbilt rating scales, etc.
Studies using objective methods to characterize sleep in adolescent
PTSD are scarce. The limited number of studies using actigraphic
investigations of pediatric PTSD suggests that this population
experiences increased sleep onset latency, nocturnal activity, and
Table 7.6 The Primary care PTSD screen (PC-PTSD)

Description: The PC-PTSD is a 4-item screen that was designed for use in
primary care and other medical settings and is currently used to screen for
PTSD in veterans at the VA. The screen includes an introductory sentence to
cue respondents to traumatic events. The authors suggest that in most
circumstances the results of the PC-PTSD should be considered “positive” if
a patient answers “yes” to any 3 items. Those screening positive should then
be assessed with a structured interview for PTSD. The screen does not
include a list of potentially traumatic events
Scale instructions: In your life, have you ever had any experience that was so
frightening, horrible, or upsetting that, in the past month, you:
1. Have had nightmares about it or thought about it when you did not want
to? YES/NO
2. Tried hard not to think about it or went out of your way to avoid situations
that reminded you of it? YES/NO
3. Were constantly on guard, watchful, or easily startled? YES/NO
4. Felt numb or detached from others, activities, or your surroundings? YES/NO
Current research suggests that the results of the PC-PTSD should be
considered “positive” if a patient answers “yes” to any 4 items
fragmentation of sleep [47]. However, it appears that the presence

of trauma rather than fully formed PTSD is associated with these
sleep changes. There are no studies using polysomnography data
for adolescent PTSD.
Treatment of adolescent PTSD using medications is mostly
extrapolated from the treatment approaches in adult PTSD. While
SSRIs are approved for treatment of depression and anxiety in
adolescents, there are no large controlled trials to support their use
in adolescent PTSD. However, they are primarily used to treat the
comorbid affective symptoms based on the preliminary evidence
that SSRIs may also be effective in adolescent PTSD. Due to the
multiplicity of symptom complex, different medications are used
for specific target symptoms, such as intrusiveness, aggression,
sleep disturbances, and dissociative symptoms. Additional phar-
macologic agents that are used empirically to treat these symptoms
in children and adolescents include alpha agonists (Guanfacine,
Clonidine), beta-blockers (Propranolol), mood stabilizers
(Carbamazepine, Valproic acid), and atypical antipsychotic medi-
cations (Quetiapine) [48–50]. Prazosin, an adrenergic-inhibiting
agent, is a promising agent for cases of PTSD where nightmares
and insomnia are prominent symptoms and has shown efficacy in
adult population. There have been case reports in adolescents with

PTSD-related nightmares with successful outcomes on treatment
with Prazosin, but no other data with larger sample size or random-
ized controlled studies are available [51–53].
Trauma-focused psychotherapies have the most empirical sup-
port in the treatment of pediatric PTSD. One of the most com-
monly used modality, Trauma-Focused Cognitive-Behavioral
Therapy (TF-CBT), is a conjoint parent–child treatment developed
that uses cognitive–behavioral principles and exposure techniques
to prevent and treat posttraumatic stress, depression, and behav-
ioral problems [54]. There are five core components of TF-CBT
including psychoeducation; coping strategies, such as relaxation,
identification of feelings, and cognitive coping; gradual exposure,
for example, through imagining or in vivo exposure; cognitive pro-
cessing; and caregiver participation, such as parent training and
conjoint sessions. The TF-CBT has been widely accepted as
evidence-based therapeutic modality, due to its effectiveness and
applicability to various trauma types, growing evidence base, and
active dissemination, which includes web-based training and
implementation in group setting [55]. Another therapy, Eye move-
ment desensitization and reprocessing (EMDR), uses cognitive
therapy with directed eye movements and has shown effectiveness
in children with PTSD especially when combined with CBT [56].
Clinical Pearls and Pitfalls: PTSD
• Symptoms of hypervigilance including sleep complaints are a

hallmark feature of PTSD.
• Evaluation and treatment of sleep disturbances associated with
PTSD helps to reduce hyperarousal and improve long-term
outcomes in adolescents with PTSD.
Learning Points
• Sleep disturbances, including sleep initiation and maintenance

insomnia and trauma-related nightmares, are essential features
of PTSD.
• Sleep evaluation is part of the comprehensive assessment of

adolescents that present with symptoms of PTSD.
• Studies of traumatized youth have indicated that trauma con-
tributes to sleep problems (especially nightmares) beyond the
diagnosis of PTSD.
• Effective treatment of sleep-related symptoms like Cognitive-
Behavioral Therapy for insomnia and Imagery Rehearsal
Therapy for nightmares improves long-term outcomes in ado-
lescents with PTSD.

References
1. Birmaher B, Birmaher B, Brent D, et al. Practice parameter for the assess-
ment and treatment of children and adolescents with depressive disorders.
J Am Acad Child Adolesc Psychiatry. 2007;46(11):1503–26. doi:10.1097/
chi.0b013e318145ae1c.
2. American Psychiatric Association. Diagnostic and statistical manual of
mental disorders, 5th ed. (DSM-5); 2013. doi:10.1176/appi.books.
9780890425596.744053.
3. Ryan ND, Puig-Antich J, Ambrosini P, et al. The clinical picture of major
depression in children and adolescents. Arch Gen Psychiatry.
1987;44(10):854–61. doi:10.1001/archpsyc.1987.01800220016003.
4. Roberts RE, Lewinsohn PM, Seeley JR. Symptoms of DSM-III-R major
depression in adolescence: evidence from an epidemiological survey.
J Am Acad Child Adolesc Psychiatry. 1995;34(12):1608–17.
doi:10.1097/00004583-199512000-00011.
5. Liu X, Buysse DJ, Gentzler AL, et al. Insomnia and hypersomnia associ-
ated with depressive phenomenology and comorbidity in childhood
depression. Sleep. 2007;30(1):83–90.
6. Patten CA, Choi WS, Gillin JC, Pierce JP. Depressive symptoms and ciga-
rette smoking predict development and persistence of sleep problems in
US adolescents. Pediatrics. 2000;106(2), E23. doi:10.1542/peds.106.2.e23.
7. Szklo-Coxe M, Young T, Peppard PE, Finn LA, Benca RM. Prospective
associations of insomnia markers and symptoms with depression. Am
J Epidemiol. 2010;171(6):709–20. doi:10.1093/aje/kwp454.
8. Gregory AM, O’Connor TG. Sleep problems in childhood: a longitudinal
study of developmental change and association with behavioral problems.
J Am Acad Child Adolesc Psychiatry. 2002;41(8):964–71. doi:10.1097/
00004583-200208000-00015.
9. Gregory AM, Rijsdijk FV, Lau JYF, Dahl RE, Eley TC. The direction of
longitudinal associations between sleep problems and depression symp-
toms: a study of twins aged 8 and 10 years. Sleep. 2009;32(2):189–99.
10. Hayley AC, Skogen JC, Sivertsen B, et al. Symptoms of depression and
difficulty initiating sleep from early adolescence to early adulthood: a lon-
gitudinal study. Sleep. 2015;38(10):1599–606. doi:10.5665/sleep.5056.
11. Roberts RE, Duong HT. Depression and insomnia among adolescents: a
prospective perspective. J Affect Disord. 2013;148(1):66–71. doi:10.1016/
j.jad.2012.11.049.
12. Sivertsen B, Harvey AG, Lundervold AJ, Hysing M. Sleep problems and
depression in adolescence: results from a large population-based study of
Norwegian adolescents aged 16–18 years. Eur Child Adolesc Psychiatry.
2013;28(3):681–9.
13. AACAP. Facts for families teen suicide. http://www.aacap.org/AACAP/
Families_and_Youth/Facts_for_Families/Facts_for_Families_Pages/
Teen_Suicide_10.aspx.
14. Liu X. Sleep and adolescent suicidal behavior. Sleep. 2004;27(7):1351–8.
15. Barbe RP, Williamson DE, Bridge JA, et al. Clinical differences between
suicidal and nonsuicidal depressed children and adolescents. J Clin
Psychiatry. 2005;66(4):492–8. doi:10.4088/JCP.v66n0412.
16. Goldstein TR, Brent DA, Bridge JA. Sleep disturbance preceding com-
pleted suicide in adolescents. Int J Emerg Ment Health. 2008;10(2):155–6.
doi:10.1037/0022-006X.76.1.84.
17. Pigeon WR, Pinquart M, Conner K. Meta-analysis of sleep disturbance
and suicidal thoughts and behaviors. J Clin Psychiatry. 2012;73(9):e1160–
7. doi:10.4088/JCP.11r07586.
18. Augustinavicius JLS, Zanjani A, Zakzanis KK, Shapiro CM.
Polysomnographic features of early-onset depression: a meta-analysis.
J Affect Disord. 2014;158:11–8. doi:10.1016/j.jad.2013.12.009.
19. Armitage R, Hoffmann R, Emslie G, Rintelman J, Moore J, Lewis K.
Rest-activity cycles in childhood and adolescent depression. J Am
Acad Child Adolesc Psychiatry. 2004;43(6):761–9. doi:10.1097/01.
chi.0000122731.72597.4e.
20. Kroenke K, Spitzer RL. The PHQ-9: a new depression measure. Psychiatr
Ann. 2002;32(9):509–15.
21. Gilbody S, Richards D, Brealey S, Hewitt C. Screening for depression in
medical settings with the Patient Health Questionnaire (PHQ): a diagnos-
tic meta-analysis. J Gen Intern Med. 2007;22(11):1596–602. doi:10.1007/
s11606-007-0333-y.
22. Posner K, Brown GK, Stanley B, et al. The Columbia-suicide severity
rating scale: initial validity and internal consistency findings from three
multisite studies with adolescents and adults. Am J Psychiatry.
2011;168(12):1266–77. doi:10.1176/appi.ajp.2011.10111704.
23. Garrison CZ, Addy CL, Jackson KL, McKeown RE, Waller JL. The CES-D
as a screen for depression and other psychiatric disorders in adolescents. J Am
Acad Child Adolesc Psychiatry. 1991;30(4):636–41. doi:S0890-8567
(09)64332-X [pii]\r10.1097/00004583-199107000-00017.
24. March JS, Silva S, Petrycki S, et al. The treatment for adolescents with
depression study (TADS): long-term effectiveness and safety outcomes. Arch
Gen Psychiatry. 2007;64(10):1132–43. doi:10.1001/archpsyc.64.10.1132.
25. Brent D, Emslie G, Clarke G, et al. Switching to another SSRI or to ven-
lafaxine with or without cognitive behavioral therapy for adolescents with
SSRI-resistant depression: the TORDIA randomized controlled trial.
JAMA. 2008;299(8):901–13. doi:10.1016/S0084-3954(08)79063-8.
26. Manglick M, Rajaratnam SM, Taffe J, Tonge B, Melvin G. Persistent
sleep disturbance is associated with treatment response in adolescents
with depression. Aust N Z J Psychiatry. 2013;47(6):556–63. doi:10.1177/
0004867413481630.
27. Drago A. SSRIs impact on sleep architecture: guidelines for clinician use.
Clin Neuropsychiatry. 2008;5(3):115–31.
28. Shamseddeen W, Clarke G, Keller MB, et al. Adjunctive sleep medica-
tions and depression outcome in the treatment of serotonin-selective reup-
take inhibitor resistant depression in adolescents study. J Child Adolesc
Psychopharmacol. 2012;22(1):29–36. doi:10.1089/cap.2011.0027.
29. Manber R, Edinger JD, Gress JL, San Pedro-Salcedo MG, Kuo TF, Kalista
T. Cognitive behavioral therapy for insomnia enhances depression out-
come in patients with comorbid major depressive disorder and insomnia.
Sleep. 2008;31(4):489–95.
30. Kessler RC, Avenevoli S, Costello J, et al. Severity of 12-month DSM-IV
disorders in the national comorbidity survey replication adolescent sup-
plement. Arch Gen Psychiatry. 2012;69(4):381–9. doi:10.1001/archgen-
psychiatry.2011.1603.Severity.
31. Kilpatrick DG, Acierno R, Saunders B, Resnick HS, Best CL, Schnurr PP.
Risk factors for adolescent substance abuse and dependence: data from a
national sample. J Consult Clin Psychol. 2000;68(1):19–30. doi:10.1037//
0022-006X.68.1.19.
32. Ohayon MM, Shapiro CM. Sleep disturbances and psychiatric disorders
associated with posttraumatic stress disorder in the general population.
Compr Psychiatry. 2000;41(6):469–78. doi:10.1053/comp.2000.16568.
33. Cohen JA, Bukstein O, Walter H, et al. Practice parameter for the assess-
ment and treatment of children and adolescents with posttraumatic stress
disorder. J Am Acad Child Adolesc Psychiatry. 2010;49(4):414–30.
doi:10.1016/j.jaac.2009.12.020.
34. Brown TH, Mellman TA, Alfano CA, Weems CF. Sleep fears, sleep distur-
bance, and PTSD symptoms in minority youth exposed to Hurricane
Katrina. J Trauma Stress. 2011;24(5):575–80. doi:10.1002/jts.20680.
35. Lonigan CJ, Phillips BM, Richey JA. Posttraumatic stress disorder in chil-
dren: diagnosis, assessment, and associated features. Child Adolesc
Psychiatr Clin N Am. 2003;12:171–94.
36. Bader K, Schäfer V, Schenkel M, Nissen L, Schwander J. Adverse childhood
experiences associated with sleep in primary insomnia. J Sleep Res.
2007;16(3):285–96. doi:10.1111/j.1365-2869.2007.00608.x.
37. Copeland WE, Keeler G, Angold A, Costello EJ. Traumatic events and
posttraumatic stress in childhood. Arch Gen Psychiatry. 2007;64(5):577–
84. doi:10.1016/S0084-3970(08)79296-X.
38. Alfano CA, Pina AA, Zerr AA, Villalta IK. Pre-sleep arousal and sleep
problems of anxiety-disordered youth. Child Psychiatry Hum Dev.
2010;41(2):156–67. doi:10.1007/s10578-009-0158-5.
39. Schreck KA, Mulick JA, Rojahn J. Parent perception of elementary school
aged children’s sleep problems. J Child Fam Stud. 2005;14(1):101–9.
doi:10.1007/s10826-005-1125-9.
40. Forbes EE, Bertocci MA, Gregory AM, et al. Objective sleep in pediatric
anxiety disorders and major depressive disorder. J Am Acad Child Adolesc
Psychiatry. 2008;47(2):148–55. doi:10.1097/chi.0b013e31815cd9bc.
41. Chase RM, Pincus DB. Sleep-related problems in children and adoles-
cents with anxiety disorders. Behav Sleep Med. 2011;9(4):224–36.
doi:10.1080/15402002.2011.606768.
42. Talamini LM, Bringmann LF, de Boer M, Hofman WF. Sleeping worries
away or worrying away sleep? Physiological evidence on sleep-emotion inter-
actions. PLoS One. 2013;8(5), e62480. doi:10.1371/journal.pone.0062480.
43. Gregory AM, Caspi A, Eley TC, Moffitt TE, O’Connor TG, Poulton
R. Prospective longitudinal associations between persistent sleep problems
in childhood and anxiety and depression disorders in adulthood. J Abnorm
Child Psychol. 2005;33(2):157–63. doi:10.1007/s10802-005-1824-0.
44. Sonis J. PTSD in primary care—an update on evidence-based management.
Curr Psychiatry Rep. 2013;15(7):373. doi:10.1007/s11920-013-0373-4.
45. Broome MV. Comparison of the Trauma symptom checklist for children,
UCLA PTSD index, and child behavior checklist in children with a trauma
history. ProQuest Diss Theses; 2009. http://search.proquest.com/docview
/305071472?accountid=14553\n; http://openurl.library.uiuc.edu/sfxlcl3?
url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&ge
nre=dissertations+&+theses&sid=ProQ:ProQuest+Dissertations+&+The
ses+Full+Text&atit.
46. Foa EB, Johnson KM, Feeny NC, Treadwell KRH. The child PTSD symp-
tom scale: a preliminary examination of this psychometric properties.
J Clin Child Adolesc Psychol. 2010;30(3):376–84. doi:10.1207/
S15374424JCCP3003_9.
47. Kovachy B, O’Hara R, Hawkins N, et al. Sleep disturbance in pediatric
PTSD: current findings and future directions. J Clin Sleep Med.
2013;9(5):501–10. doi:10.5664/jcsm.2678.
48. Connor DF, Grasso DJ, Slivinsky MD, Pearson GS, Banga A. An open-
label study of guanfacine extended release for traumatic stress related
symptoms in children and adolescents. J Child Adolesc Psychopharmacol.
2013;23(4):244–51. doi:10.1089/cap.2012.0119.
49. Stathis S, Martin G, McKenna JG. A preliminary case series on the use
of quetiapine for posttraumatic stress disorder in juveniles within a
youth detention center. J Clin Psychopharmacol. 2005;25(6):539–44.
doi:00004714-200512000-00006 [pii].
50. Donnelly CL. Pharmacologic treatment approaches for children and

adolescents with posttraumatic stress disorder. Child Adolesc Psychiatr
Clin N Am. 2003;12(2):251–69. doi:10.1016/S1056-4993(02)00102-5.
51. Kung S, Espinel Z, Lapid MI. Treatment of nightmares with prazosin: a
systematic review. Mayo Clin Proc. 2012;87(9):890–900. doi:10.1016/j.
mayocp.2012.05.015.
52. Strawn JR, DelBello MP, Geracioti TDJ. Prazosin treatment of an adoles-
cent with posttraumatic stress disorder. J Child Adolesc Psychopharmacol.
2009;19:599–600. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=ref
erence&D=psyc6&NEWS=N&AN=2009-20848-019.
53. Fraleigh LA, Hendratta VD, Ford JD, Connor DF. Prazosin for the treat-
ment of posttraumatic stress disorder-related nightmares in an adolescent
male. J Child Adolesc Psychopharmacol. 2009;19(4):475–6. doi:10.1089/
cap.2009.0002.
54. Cohen JA, Mannarino AP, Perel JM, Staron V. A pilot randomized con-
trolled trial of combined trauma-focused CBT and setraline for childhood
PSTD symptoms. J Am Acad Child Adolesc Psychiatry. 2007;46(7):811–9.
doi:10.1097/chi.0b013e3180547105.
55. De Arellano MAR, Lyman DR, Jobe-Shields L, et al. Trauma-focused cog-
nitive-behavioral therapy for children and adolescents: assessing the evi-
dence. Psychiatr Serv. 2014;65(3):1–12. doi:10.1176/appi.ps.201300255.
56. Rodenburg R, Benjamin A, de Roos C, Meijer AM, Stams GJ. Efficacy
of EMDR in children: a meta-analysis. Clin Psychol Rev. 2009;29(7):
599–606. doi:10.1016/j.cpr.2009.06.008.
Medical Disorders
8
Vicky Chiang and Alcibiades J. Rodriguez
Abbreviations
AHI Apnea/hypopnea index

BMI Body mass index
CBC Complete blood count
CMP Comprehensive metabolic panel
CPAP Continuous positive airway pressure
ENT Ear nose and throat
ESS Epworth sleepiness scale
OSA Obstructive sleep apnea
PLMS Periodic limb movements of sleep
PSG Polysomnogram
RLS Restless legs syndrome
TPO Thyroid peroxidase
TSH Thyroid-stimulating hormone
V. Chiang, B.S.
Department of Neurology, New York University Medical School,
16019 Crestline Dr., La Mirada, CA 90638, USA
e-mail: vc936@nyumc.org
A.J. Rodriguez, M.D. (*)
Department of Neurology, New York University Medical School,
724 Second Avenue, New York, NY 10016, USA
e-mail: alcibiades.rodriguez@nyumc.org

120 V. Chiang and A.J. Rodriguez
Clinical Case 1
The patient is a 14-year-old boy with a history of asthma referred to

the sleep clinic for evaluation of excessive daytime sleepiness. He
has just started the ninth grade and has been struggling in his classes
as he is unable to stay awake. His parents are concerned as he was
previously a very good student.
The patient states that his daytime sleepiness started about
4 months ago, around the same time school started. He reports that
he frequently falls asleep during class and always feels tired despite
having adequate sleep or going to bed earlier than usual. Even when
he is not in school, he often nods off throughout the day. He denies
having any difficulty falling asleep at night or staying asleep through-
out the night. He denies any abnormal movements or snoring. He
normally goes to bed between 10 and 11 pm and wakes up at 7 am,
though he admits that he occasionally stays up late at night playing
computer games. He may sleep longer on weekends, but still feels
sleepy. He does not snore and he is quiet during sleep. He frequently
takes 1-h naps after school, but wakes up feeling unrefreshed.
He was first diagnosed with asthma at the age of 6. He has mod-
erate persistent asthma for which he takes fluticasone 2 puffs twice
daily. However, since school started, he has been less compliant
with his medication because he is often rushed in the mornings. He
denies any drug and caffeine use. He states that his only stressor is
his current academic issues, but he is otherwise well-liked by his
teachers, has many friends in school, and is on the soccer team.
On physical exam, he is a tired-appearing, thin, pre-pubescent
male. His blood pressure is 107/75, pulse is 72 per minute and
regular. He is 163 cm tall and weighs 52.1 kg with a Body Mass
Index (BMI) of 19.6. Lung, heart, abdomen, and neurological
exam do not reveal any abnormalities.
Discussion
This 14-year-old patient has a long-standing history of asthma that

appears to be poorly controlled in recent months, likely secondary
to medication non-adherence. In this case, it is reasonable to sus-
pect that this patient’s symptoms are a consequence of asthma,
8 Medical Disorders 121
though it is important to rule out other common causes of adoles-

cent sleep disturbances first. A detailed history assessing nighttime
asthma symptoms and environmental or social triggers is crucial
because acute exacerbations often lead to frequent nighttime
awakenings and decreased quality of sleep in asthmatics [1].
Many asthmatics have worsened symptoms at night due to
increased bronchial hyper-reactivity, airway inflammation, and air-
way resistance. Patients may awaken in the night coughing, wheez-
ing, or feeling short of breath. These nocturnal asthma symptoms
are indicative of inadequate asthma control. As a result, children
with asthma often report daytime sleepiness, difficulty maintaining
sleep, and early morning awakenings [2]. Adolescents with asthma
also report insufficient sleep, poor sleep hygiene, and insomnia
[1]. In these youths with nocturnal asthma symptoms, sleep poly-
somnography normally shows frequent nighttime awakenings [3].
Other sleep complaints, such as, early morning awakenings and
restless sleep have been associated with asthma (Table 8.1).
Interestingly, about 71 % of patients with asthma also suffer from
allergic rhinitis, which also has an independent association with
sleep disturbances. Therefore, concurrent allergic rhinitis may be
an important cause of sleep disturbances in asthmatics [4].
These sleep disruptions are associated with significant morbid-
ity. Numerous studies have found that children with poorly con-
trolled asthma have overall lower quality of life with impairment
in their social and academic activities and adverse effects on their
psychological and emotional states. Presence of nocturnal symp-
toms is a particularly poor prognostic indicator. Asthmatic chil-
dren with increased nocturnal symptoms have been found to have
poorer sleep quality, more time awake at night, and lower scores
Table 8.1 Most common • Difficulties inducing sleep (12.7 %)

sleep complaints in asthma
• Early morning awakenings (11.2 %)
• Daytime sleepiness (25 %)
• Snoring (14.7–46 %)
• Self-reported apneas (OR = 3.7)
• Restless sleep (26 %)
• Nocturnal awakenings (30 %)
• Apnea (3.8–6 %)
• Daytime tiredness (17–23.2 %)
on tests of daytime cognitive performance [5]. They have poorer

school attendance and performance and their parents’ work atten-
dances are negatively impacted as well [6].
Treatment for asthma-related sleep disturbances is simply
improved asthma control. The importance of this must be empha-
sized, as about 34–40 % of asthmatic children experience nocturnal
awakening, and those children with poorly controlled asthma are sig-
nificantly more likely to have more nocturnal awakenings per week
compared to their well-controlled counterparts [7]. Studies done in
adolescents have also shown higher rates of sleep disturbances in
those with severe asthma compared to those with mild asthma [8, 9].
Thus, an important part of the treatment includes: adjusting the
patient’s medication regimen, educating the patient and family on
medication compliance, and avoiding environmental triggers that
may cause an acute exacerbation or worsen nocturnal symptoms.
Pitfalls
• Asthma-related sleep disturbance may be challenging to distin-

guish from other common adolescent sleep disorders and they
may be co-occurring as well.
• Many youths presenting with sleep disturbances may also have
undiagnosed asthma.
Learning Points
• In asthmatic youths, a detailed history assessing medication

compliance, potential environmental triggers, and presence of
nocturnal asthma is crucial when asthma-related sleep distur-
bance is suspected.
• Concurrent allergic rhinitis may be an important cause of sleep
disturbances in asthmatics.
• Presence of nocturnal asthma is a poor prognostic indicator for
daytime functioning in children
• Treatment for asthma-related sleep disturbances is adequate
control of asthma.
Clinical Case 2
The patient is a 13-year-old girl who was recently diagnosed with

obstructive sleep apnea (OSA) and started on Continuous Positive
Airway Pressure (CPAP), now presenting with continued com-
plaints of lethargy, daytime sleepiness, and poor concentration
over the past several weeks. She initially presented about 3 months
ago with similar symptoms and complaints of snoring and frequent
night awakenings. A polysomnography (PSG) was done at that
time which showed severe OSA. She subsequently underwent an
adenotonsillectomy which failed to relieve her symptoms. As a
result, she was started on CPAP about 2 months ago with marked
improvement. However, over the past few weeks, she has begun to
feel poorly again with additional complaints of muscle aches and
constipation. She states that she is compliant with using CPAP
every night, which her parents verify. Her compliance report shows
a usage of 9–10 h with no residual sleep disordered breathing. She
does sleep approximately 9.5 h every night. She denies any further
daytime sleepiness, but continues to feel fatigued and unable to
tolerate much physical activity in school.
On physical exam, she is an obese, prepubescent female who is
short for her age. Her hair and skin appear dry and brittle. Her
thyroid feels mildly enlarged on exam. Her neurological exam is
otherwise unremarkable.
Complete blood count (CBC) and comprehensive metabolic
panel (CMP) returned normal. Thyroid-stimulating hormone
(TSH) returned elevated and free T4 was low. Patient also had high
thyroid peroxidase (TPO) antibody levels. A diagnosis of autoim-
mune thyroiditis was made and she was subsequently started on
thyroxine with resolution of her symptoms. She continues on
CPAP for her OSA.
Discussion
This patient has OSA, most likely secondary to her hypothyroid-

ism. OSA is a fairly common pediatric disorder, occurring in about
1–4 % of children and is particularly prevalent between the ages of
2 and 8 years [10]. In the pediatric population, it is usually second-

ary to lymphoid hyperplasia and adeno-tonsillar hypertrophy, so it
often resolves with an adenotonsillectomy. However, OSA is also
frequently associated with many other medical conditions such as
hypothyroidism, as is the case here. Hypothyroidism is of special
significance in the pediatric and adolescent population as it is the
most common thyroid disorder. It is usually secondary to autoim-
mune thyroiditis, though may also be congenital or secondary to
drugs or iodine deficiency.
Several studies have cited an increased prevalence of OSA in
hypothyroidism. It has been theorized that this is likely a result of
obesity, macroglossia, upper respiratory tract myopathy, deposi-
tion of mucopolysaccharides in the upper respiratory tract, and
decreased central ventilatory control [11, 12]. However, it remains
controversial whether or not to screen for hypothyroidism in
patients presenting with OSA given that there is a subset of the
population with both disorders [13]. Furthermore, OSA and
hypothyroidism have overlapping clinical pictures which may
make it difficult to distinguish between the two (Table 8.2).
Nevertheless, though it is accepted that there is a significantly
higher occurrence of sleep apnea in hypothyroid patients, the
inverse has not found to be true, with several studies finding no
significant difference in the prevalence of hypothyroidism
between patients with sleep apnea and the general population
[14]. Thus, current guidelines do not recommend screening for
hypothyroidism in patients with OSA [15].
It is unclear whether the treatment of the hypothyroidism with
thyroid hormone replacement therapy leads to improvement of
sleep apnea in patients with hypothyroidism-associated OSA.
Several studies have been done with contrasting results, with some
researchers reporting resolution of OSA after thyroxine treatment
and others reporting persistent apnea with continued CPAP
requirement in spite of correction of thyroid abnormalities [16,
17]. In any case, treatment for hypothyroidism-associated OSA
should be no different from the typical management of the two
disorders when they occur independently.
Table 8.2 Obstructive sleep apnea (OSA) and hypothyroidism clinical features
Clinical OSA Hypothyroidism
Obestiy Yes Yes
Sleepiness Variable in children, Mostly fatigue
hyperactive
Snoring Most of the time Variable, present if OSA
Thyroid levels Normal Abnormal
Enlarged thyroid No Variable
Systemic None usually Constipation, slow reflexes, brittle
manifestations hair, sensitivity to cold increased
Depression At times if severe Frequent
Cognition Decreased attention, Impaired memory if severe,
hyperactive, irritable irritable
Pitfalls
• OSA and hypothyroidism may be challenging to distinguish as

patients often have overlapping symptoms and the two also fre-
quently occur together.
• Patients with OSA do not need to be screened for hypothyroid-
ism unless there is increased clinical suspicion.
• It is unclear whether adequate thyroid replacement therapy
leads to improvement of OSA symptoms.
Learning Points
• There is an increased prevalence of OSA in patients with hypo-

thyroidism than the general population, so clinicians should
screen for OSA by taking a thorough history.
• Treatment of hypothyroidism-associated OSA is simply treat-
ment of hypothyroidism and of OSA.
Clinical Case 3
Sixteen year-old girl who presents with his mother due to exacerba-
tion of migraine headaches for the last two months. She has had
headaches since age 11. These headaches are throbbing, unilateral
(either left or right side), associated with nausea and, at times, vomit.
She mentions phonophobia and photophobia associated with them.
The typical headaches occur, at least, once a week and last from
4–12 h if untreated, but she also has chronic daily headaches, which
may last the whole day if untreated. In the past, the headaches
occurred once or twice a year. She has tried acetaminophen and ibu-
profen for these headaches with no success. She has been given
butalbital/acetaminophen/caffeine tablets with resolution of her
headaches, but these return quickly after the effect wears off. She
takes this medication several times a day. She was recommended to
take valproic acid for headache prevention, but she did not like the
side effects profile and she did not take it.
Her mother and paternal aunt have a history of migraines. Her
past medical history is significant for having heavy menstrual peri-
ods since 1 year ago and significant weight gain. She sleeps from
10–11 PM and she does not have any problems to fall or stay asleep.
She wakes up at 7:00 AM with help of an alarm clock. She snores
loudly every night and she is very restless sleeper. She has noted
being more tired lately. Her Epworth Sleepiness Scale (ESS) is
10/24. There has been a minor decrease in grades at school and she
seems irritable at times.
Her physical exam is normal, except for her weight at 95 kg;
height is 152.4 cm. This accounts for a BMI of 40.9. Upon more
questioning, she also admits feeling a “crawly” feeling in legs at
night or when sitting quietly. She feels better moving the legs.
Discussion
The intimate connection between sleep and headaches has been rec-
ognized for centuries. Pain stimuli and pain disorders may affect
sleep quality and quantity. One of the most common triggers for
headaches is sleep deprivation [18, 19], and it is well-known that
sleep can terminate migraine attacks [18].
There are different ways a headaches and sleep interact
(Table 8.3). First, sleep deprivation may be the cause of headaches.
This headache is usually dull and localized in the frontal head
regions [20]. A sleep disorder, such as, OSA can produce morning
Table 8.3 Headaches and Sleep disorders as a cause or exacerbation

sleep interaction of headaches
Headaches as a cause of sleep disturbances
Medical disorders sharing headaches and
sleep disturbances
type headaches, usually generalized and dull, which subsides on

its own as the day continues. Up to half of patients with OSA may
have this type of headache [21]. The prevalence of migraine in
patients with Restless Legs Syndrome (RLS) has been reported to
be 16.9 % compared to 8.7 % in controls. RLS is also more severe
in patients with migraine. This could be related to reports that
sleep quality is decreased in patients with migraine and headaches
compared to controls [22].
There are headaches that also may occur during sleep, such as,
migraine, cluster headaches, and chronic paroxysmal hemicrania
[23]. Hypnic headaches are defined in part by occurrence only in
sleep [23, 24]. Exploding head syndrome, despite its name, is not
a headache. It is characterized by sudden loud noise or sense of
explosion in the head occurring in the wake-sleep transition or
upon waking up at night. There is an abrupt arousal and sensation
of fear and it is not significant pain complaint [25].
Headaches also can affect sleep quality and quantity [18, 19].
Chronic tension type headaches are associated with subjective and
objective evidence of fragmented sleep and excessive daytime
sleepiness [26]. Other disorders, such as, depression and fibromyal-
gia may be accompanied of headaches and sleep disturbances.
Often, these two issues are related to the underlying primary disease
entity [18]. Of note, patients with chronic headaches and sleep dis-
orders, such as, insomnia may also lead to anxiety and depression
[27] (Fig. 8.1).
Our patient meets criteria for migraine headache without aura:
(1) at least 5 attacks; (2) duration 4–72 h (untreated or unsuccess-
fully treated); (3) Unilateral and pulsating; (4) nausea, vomiting,
photophobia, and phonophobia [24]. She also meets criteria for
medication-overuse headache: (1) headache occurring on ≥15 days
per month in a patient with preexisting headache disorder; (2) regu-
lar overuse for >3 months or one of more drugs for acute headache
treatment [24]. Migraine is one of the most common types of
Headaches
Migraine
Tension type
Others
Disrupted sleep Medical conditions

Sleep deprivation Fibromyalgia
Sleep disorders Depresssion
Others
Fig. 8.1 Relationship between headaches, disrupted sleep, and medical conditions
headaches in children. Approximately, 24–42 % of patients with

migraine have attacks related to sleep or upon awakening [19].
This patient had a PSG showing a total Apnea/hypopnea index
(AHI) of 15 with a minimal oxygen saturation of 82 %. She also
had a Periodic Limb Movements of Sleep (PLMS) index of 20.
She had an arousal index of 35. Subsequently, the patient was sent
for CPAP titration study and treatment for her OSA was started at
8 cm of water pressure. Of note, her PLMS index during titration
was similar to baseline. She was also sent for an evaluation by an
Ear-nose-throat (ENT) physician, which did not consider any sur-
gical intervention since there was no enlarged adenoids/tonsils or
anatomical deformities. She was also sent to endocrinologist and
nutritionist for appropriate evaluation and counseling about
weight loss. Her complete blood count was normal, but she had a
ferritin level of 15 ng/mL and percentage of iron saturation of
12 %. Iron supplementation was initiated. She was advised to
decrease analgesics slowly every day and offered low-dose topira-
mate for headache prophylaxis, but she declined since she did not
want to take any prescription medications.
After 2 months of treatment, her headaches were much better
with only one episode of migraine since then. She has lost 10 lb
and participates in a strict nutritional regimen. She uses CPAP
every day. Her ferritin level is now 35 ng/mL.
There is evidence in adults and adolescents that treatment of

OSA with CPAP or an oral appliance may help some patients with
mostly morning type headaches, which are typical of OSA [28,
29]. However, there is some evidence it may help to control
migraine too [30]. The mechanism of the headache is postulated to
be hypoxemia, hypercarbia, increased intracranial pressure, or
increased systemic blood pressure related to arousals [19].
One article found an improvement in migraine frequency in
50 % of patients after dopaminergic therapy for RLS [31]. Low
ferritin levels, specifically, below 50 ng/mL, correlates with RLS
and PLMS [32]. So, correcting ferritin will certainly help her RLS
and PLMS and her migraines. It is common sense that improve-
ment in sleep quantity and quality (if PLMS present) may account
for this improvement; however, more studies are needed.
The slow withdrawal of analgesics needs to be accompanied by
a prophylactic treatment and the understanding of the patient that
these medications are making the headaches worse. Our patient’s
improvement in headaches, in part, could be attributed to the con-
trol of the sleep disorders, which allowed her to be taken off the
daily analgesic use.
Pitfalls
• Physicians often see headache as an isolated entity without

careful attention to comorbidities.
• Inquiring about sleep quantity and quality is overlooked at pri-
mary care settings.
• Sleep disorders could be more than just sleep-disordered
breathing and to have a full evaluation requires sleep medicine
consultation.
Learning Points
• Clinicians must recognize that even primary headache diagno-

sis may have comorbidities that can affect headache treatment.
• A comprehensive evaluation of headaches requires inquiring
about sleep quality and quantity.
• Adequate treatment of the sleep disturbances/disorders helps

headache control and, conversely, better headache therapy
improves sleep.
Conclusions
As we can see, medical disorders can impair sleep and sleep affect
disease entities in different ways. Asthma and related conditions,
such as, allergic rhinitis may produce sleep disturbances that can
affect daytime functioning. We also have hypothyroidism, which
may be overlooked since all symptoms may be attributed to
OSA. Hypothyroidism may cause OSA due to weight gain and
macroglossia. Persistent symptoms after treated OSA or clinical
characteristics not typical of the condition may require further
evaluation (including the possibility of another sleep disorder), in
which hypothyroidism must not be forgotten. Headaches and sleep
interaction could be complex. The treatment of one disturbance
certainly will help control the other one.
A detailed evaluation of the above disorders requires sleep as
part of the clinical history and, sometimes, physical exam. A good
sleep evaluation takes into account medical comorbidities.

interest.
No off-label use of drugs or products has been discussed in the
manuscript.
References
1. Meltzer LJ, Ullrich M, Szefler SJ. Sleep duration, sleep hygiene, and
insomnia in adolescents with asthma. J Allergy Clin Immunol Pract.
2014;2(5):562–9.
2. van Maanen A, Wijga AH, Gehring U, Postma DS, Smit HA, Oort FJ,
et al. Sleep in children with asthma: results of the PIAMA study. Eur
Respir J. 2013;41(4):832–7.
3. Stores G, Ellis AJ, Wiggs L, Crawford C, Thompson A. Sleep and psycho-
logical disturbance in nocturnal asthma. Arch Dis Child. 1998;78(5):
413–9.
4. Janson C, De Backer W, Gislason T, Plaschke P, Bjornsson E, et al.

Increased prevalence of sleep disturbances and daytime sleepiness in sub-
jects with bronchial asthma: a population study of young adults in three
European countries. Eur Respir J. 1996;9(10):2132–8.
5. Fitzpatrick MF, Engleman H, Whyte KF, Deary IJ, Shapiro CM, Douglas
NJ. Morbidity in nocturnal asthma: sleep quality and daytime cognitive
performance. Thorax. 1991;46(8):569–73.
6. Diette GB, Markson L, Skinner EA, Nguyen TT, Algatt-Bergstrom P, Wu
AW. Nocturnal asthma in children affects school attendance, school per-
formance, and parents’ work attendance. Arch Pediatr Adolesc Med.
2000;154(9):923–8.
7. Dean BB, Calimlim BC, Sacco P, Aguilar D, Maykut R, Tinkelman
D. Uncontrolled asthma among children: impairment in social functioning
and sleep. J Asthma. 2010;47(5):539–44.
8. Li Z, Huang IC, Thompson L, Tuli S, Huang W, DeWalt D, et al. The rela-
tionships between asthma control, daytime sleepiness, and quality of life
among children with asthma: a path analysis. Sleep Med. 2013;14(7):641–7.
9. Desager KN, Nelen V, Weyler JJJ, De Backer WA. Sleep disturbance and
daytime symptoms in wheezing school-aged children. J Sleep Res.
2005;14(1):77–82.
10. Marcus CL. Sleep-disordered breathing in children. Am J Respir Crit Care
Med. 2001;164(1):16–30.
11. Mete T, Yalcin Y, Berker D, Ciftci B, Guyen Firat S, Topaloglu O, et al.
Relationship between obstructive sleep apnea and thyroid disease.
Endocrine. 2013;44(3):723–8.
12. Parker DC, Pekary AE, Hershman JM. Effect of normal and reversed
sleep-wake cycles upon nyctohemeral rhythmicity of plasma thyrotropin:
evidence suggestive of an inhibitory influence in sleep. J Clin Endocrinol
Metab. 1976;43(2):318–29.
13. Takeuchi S, Kitamura T, Ohbuchi T, Koizumi H, Takahashi R, Hohchi N,
et al. Relationship between sleep apnea and thyroid function. Sleep Breath.
2015;19(1):85–9.
14. Lin CC, Tsan KW, Chen PJ. The relationship between sleep apnea syn-
drome and hypothyroidism. Chest. 1992;102(6):1663–7.
15. Marcus CL, Brooks LJ, Draper KA, Gozal D, Halbower AC, Jones J, et al.
Diagnosis and management of childhood obstructive sleep apnea syn-
drome. Pediatrics. 2012;130(3):576–84.
16. Grustein RR, Sullivan CE. Sleep apnea and hypothyroidism: mechanisms
and management. Am J Med. 1988;85(6):775–9.
17. Mickelson SA, Lian T, Rosenthal L. Thyroid testing and thyroid hormone
replacement in patients with sleep disordered breathing. Ear Nose Throat
J. 1999;78(10):768–75.
18. Dodick DW, Eross EJ, Parish JM. Clinical, anatomical, and physiological
relationship between sleep and headache. Headache. 2003;43(3):282–92.
19. Guidetti V, Dosi C, Bruni O. The relationship between sleep and headache
in children: implications for treatment. Cephalalgia. 2014;34(10):767–76.
20. Blau JN. Sleep deprivation headache. Cephalalgia. 1990;10(4):157–60.

21. Cao MT, Guilleminault C, Kushida CA. Clinical features and evaluation
of obstructive sleep apnea (OSA) and upper airway resistance syndrome.
In: Kryger MH, Roth T, Dement WC, editors. Principles and practices of
sleep medicine. 5th ed. St. Louis: Elsevier; 2011. p. 1206–18.
22. van Oosterhout WP, van Someren EJ, Louter MA, Schoonman GG,
Lammers GJ, Rijsman RM, et al. Restless legs syndrome in migraine
patients: prevalence and severity. Eur J Neurol. 2016;23(6):1110–6.
doi:10.1111/ene.12993.
2014. p. 350–5.
24. Headache Classification Committee of the International Headache Society
(HIS). The international classification of headache disorders, 3rd ed. (beta
version). Cephalalgia 2013 Jul;33(9): 629–8.
2014. p. 264–6.
26. Sahota PK, Dexter JD. Sleep and headache syndromes: a clinical review.
Headache. 1990;30(2):80–4.
2014. p. 19–41.
28. Goksan B, Gunduz A, Kardeniz D, Agan K, Tascilar FN, Tan F, et al.
Morning headache in sleep apnea: clinical and polysomnographic evalua-
tion and response to nasal continuous positive airway pressure.
Cephalalgia. 2009;29(5):635–41.
29. Carra MC, Huynh NT, El-Khatib H, Remise C, Lavigne GJ. Sleep brux-
ism, snoring, and headaches in adolescents: short-term effects of a man-
dibular advancement appliance. Sleep Med. 2013;14(7):656–61.
30. Johnson KG, Siemba AM, Garb JL. Improvement in headaches with con-
tinuous positive airway pressure for obstructive sleep apnea: a retrospec-
tive analysis. Headache. 2013;53(2):333–43.
31. Suzuki K, Suzuki S, Miyamoto M, Miyamoto T, Numao A, Watanabe Y,
et al. Does pramipexole treatment improve headache in patients with con-
comitant migraine and restless legs syndrome? Tremor and other
Hyperkinet Mov. 2013;3. pii: tre-03-176-4234-1.
2014. p. 281–91.
Brain Tumors
9
Danielle M. Graef and
Valerie McLaughlin Crabtree
Clinical Case
“Henry” was a 12-year-old, right-handed, and previously healthy

biracial male who was diagnosed with craniopharyngioma (month
1 as indicated in Table 9.1) after an MRI revealed the presence of
a sellar and suprasellar mass extending to the third ventricle with
resulting obstructive hydrocephalus. Henry underwent subtotal
resection of the tumor (month 1), with the surgical pathway extend-
ing through the left anterior portion of the corpus callosum, and he
received proton therapy (months 2 through 4). Medical complica-
tions related to his craniopharyngioma and treatment included
excessive daytime sleepiness (EDS) and several endocrinopathies
(i.e., growth hormone deficiency, hypothyroidism, and adrenal
insufficiency), for which he was prescribed levothyroxine and
hydrocortisone.
Henry was followed with serial neurocognitive and sleep
assessments as part of his enrollment on a clinical research trial.
He was then referred for a clinical (non-research) psychological
assessment in month 12 due to concerns related to weaknesses in
intellectual functioning and verbal learning and memory noted
D.M. Graef, Ph.D. • V.M. Crabtree, Ph.D. (*)

Department of Psychology, St. Jude Children’s Research Hospital,
262 Danny Thomas Place, Memphis, TN 38105, USA
e-mail: danielle.graef@stjude.org; valerie.crabtree@stjude.org

134
Table 9.1 Assessment and intervention schedule

Assessment/intervention Month 1 Month 2 Month 3 Month 4 Month 12 Month 15 Month 21
Tumor resection x
Polysomnography sleep study x x
Multiple sleep latency testing x x x
Sleep questionnaires x x x
Proton beam therapy x x x
Research cognitive assessment xa x
Clinical cognitive assessment x
Modafinil intervention initiation xb
a
Prior to proton beam therapy
b
After cognitive assessment
D.M. Graef and V.M. Crabtree
9 Brain Tumors 135
during his research-based assessment prior to initiating proton

therapy (month 2), as well as because of poor academic perfor-
mance in spite of academic supports in place. See Table 9.1 for an
outline of his assessment and intervention schedule.
History
At the time of Henry’s diagnosis, concerns were denied regarding

problematic sleep and fatigue. His mother noted mild daytime
sleepiness that was not described as problematic prior to the initia-
tion of medical treatment. He was reportedly obtaining adequate
sleep (i.e., approximately 9 h per night), and there were no reported
concerns historically or at the time of diagnosis regarding sleep
hygiene, sleep onset, sleep maintenance, tonsillar hypertrophy, or
sleep-disordered breathing. There were also no concerns regarding
cataplexy, hypnagogic or hypnopompic hallucinations, or sleep
paralysis historically and across all assessment time points.
Henry received special education services for reading and speech
difficulties that predated his tumor diagnosis, though it was unclear
when the tumor first presented relative to the academic concerns,
due to the often delayed recognition of craniopharyngioma [1].
Henry’s mother reported that he continued to be “just getting by”
academically despite his relative improvements overall since proton
therapy. She also stated that his EDS interfered with his alertness
and attention in both the home and classroom settings. Henry’s
mother described concerns with his attention, distractibility,
organization, learning and memory, and speed of task completion.
Family history was significant for Attention-Deficit/Hyperactivity
Disorder (ADHD) and undiagnosed difficulties with attention.
Diagnostic Studies
At the time of his diagnosis, Henry had experienced a notable

change in his mental status, and an MRI revealed the presence of a
left subdural hematoma and large suprasellar mass (2.2 cm ×
2.4 cm × 1.3 cm) with obstructive hydrocephalus that was consis-
tent with craniopharyngioma (month 1). He experienced recurrent
136 D.M. Graef and V.M. Crabtree
subdural hematomas of varied degrees of thickness (i.e., up to

6 mm) in the left frontal and parietal regions of the brain during the
first 6 months following resection. In month 2 following his tumor
resection and prior to his research-driven cognitive evaluation, an
MRI revealed mass effect on the hypothalamus, resolution of the
hydrocephalus, and a continued subdural hematoma and moder-
ately enlarged third and lateral ventricles. A PET scan in month 2
indicated decreased uptake in the left frontal region of the brain
that was suggestive of possible hypoperfusion. His MRI in month
6 revealed decreased size of the mass, midline shift, and distorted
ventricles related to his hematoma, as well as mass effect on the
superior sagittal sinus and left frontal and parietal lobes. There
were no noted hematomas in the month 9 MRI or thereafter.
Henry’s most recent MRI at the time of his psychological assess-
ment (month 12) indicated a decrease in the size of his tumor and
an improved appearance of the subdural collections.
Initial Sleep Study and Subjective Sleep Ratings

(Month 2)
In month 2 during his baseline assessment prior to proton therapy,

Henry and his mother completed subjective sleep questionnaires,
and Henry underwent a nocturnal polysomnography (PSG) that
was followed by daytime multiple sleep latency testing (MSLT;
see Table 9.2). He received an adequate quantity of sleep during
his PSG (500.0 min), with a sleep onset latency (SOL) of 2.0 min
and a sleep efficiency of 97.1%. The distribution of his sleep stages
was atypical due to the decreased proportion of time spent in REM
sleep (i.e., 10.5%). Henry exhibited 20 spontaneous arousals, as
well as 11 respiratory-related arousals. His apnea/hypopnea (AHI)
index was 2.6 per hour of sleep, which included five obstructive
apneas and 16 hypopneas with no central or mixed apneas. Henry’s
minimum oxygen saturation (SpO2) was 95%, and seven desatura-
tions occurred over the course of the PSG. There were no periodic
limb movements during the study. On the MSLT, Henry fell asleep
at each nap opportunity. His mean sleep onset latency was 2.6 min
(Range = 0.5–4.0 min), and he exhibited sleep onset REM
(SOREM) at each opportunity (Range = 4.5–8.0 min), indicating
clinically significant hypersomnia.
9 Brain Tumors 137
Consistent with MSLT findings, Henry endorsed significant

EDS on the modified Epworth Sleepiness Scale (ESS = 12; see
Table 9.2). He did not endorse concerns regarding fatigue across
Table 9.2 Results of objective and subjective sleep assessments

PSG Month 2 Month 15 Month 21
Total time in bed 500.0 485.5 547.5
Total sleep time (TST) 485.5 429.5 527.5
Sleep onset latency 2.0 7.0 9.0
REM latency 225.5 245.0 188.0
Sleep efficiency (%) 97.1% 88.5% 96.3%
Sleep stages (percent of sleep time)
Stage N1 sleep 3.3% 1.9% 0.3%
Stage N2 sleep 50.8% 50.4% 36.9%
Stage N3 Sleep 35.4% 38.9% 52.1%
REM sleep 10.5% 8.8% 10.7%
Number of spontaneous arousals 31.0 71.0 65
Apnea/hypopnea index (AHI, events per 2.6 2.0 0.2
hour)
SpO2 minimum (%) 95.0% 93% 86%
PLM index 0.0 0.0 0.0
MSLT Month 2 Month 15 Month 21

Mean sleep onset latency (minutes) 2.6 4.75 15.0
REM onset (number per opportunity) 4/4 0/4 0/4
Nap 1 (minutes)
Sleep onset REM 4.5 N/A N/A
Nap 2 (minutes)
Nap 3 (minutes)
Nap 4 (minutes)
(continued)

Sleep questionnaires Month 2 Month 15 Month 21
Excessive daytime sleepinessa 12.0 4.0 4.0
Self-reported fatigueb
General fatigue 100 79.2 83.3
Sleep/rest fatigue 100 83.3 91.7
Cognitive fatigue 100 100 100
Total fatigue 100 87.5 91.7
Parent-proxy fatigueb
General fatigue 50.0 66.6 100
Sleep-rest fatigue 37.5 25.0 100
Cognitive fatigue 12.5 50.0 75
Total fatigue 33.3 47.2 91.7
N/A Not applicable, as REM onset did not occur
a
Higher scores equate to greater excessive daytime sleepiness
b
Higher scores indicate higher quality of life or less fatigue
any of the domains of the Pediatric Quality of Life Multidimensional

Fatigue Scale (PedsQL MFS); however, parent-proxy report indi-
cated significant fatigue across the general, sleep/rest, cognitive,
and overall fatigue domains (see Table 9.2). Henry’s mother indi-
cated that he “often” or “almost always” felt tired, felt physically
weak, slept and rested a lot, and experienced difficulties with sus-
tained attention, remembering what people told him or what he
just heard, remembering more than one thing at a time, and think-
ing quickly. No pharmacological intervention was initiated due to
the limited presence of and interference from EDS in the home and
school settings and his plan to initiate proton therapy, with recom-
mendations that symptoms be monitored.
Time Between Scheduled Sleep Assessments

(Months 6–12)
During medical follow-up at month 6, Henry’s mother indicated

that he was experiencing increased sleep problems since diagno-
sis, including fatigue, worsened daytime sleepiness, and late
9 Brain Tumors 139
afternoon napping. At the time of cognitive testing (month 12),

Henry was experiencing persistent EDS that resulted in his falling
asleep in school, and he was taking daily naps from 4–6 pm despite
a full night’s sleep (i.e., approximately 9 h, with no reported diffi-
culties with sleep initiation or maintenance). His neurologist also
recommended a follow-up sleep study (scheduled month 15) and
consideration of stimulants given Henry’s persistent EDS.
One Year Follow-Up Sleep Study and Subjective

Sleep Ratings (Month 15)
In month 15, Henry and his mother completed subjective sleep

questionnaires, and Henry underwent a repeat PSG followed by
MSLT (see Table 9.2). He received an adequate quantity of sleep
during his PSG (429.5 min), with a SOL of 7.0 min and a sleep
efficiency of 88.5%. The distribution of his sleep stages continued
to be atypical due to the decreased proportion of REM sleep (i.e.,
8.8%). Henry exhibited 66 spontaneous arousals and five respira-
tory-related arousals. His AHI index was 2.0 per hour of sleep,
which included three obstructive apneas and 11 hypopneas. Henry’s
minimum oxygen saturation (SpO2) was 93%, and 38 desaturations
occurred. There were no periodic limb movements. On the MSLT,
Henry initiated sleep at each nap opportunity. His mean sleep onset
latency was 4.75 min (Range = 1.5–6.0 min), and there were no epi-
sodes of SOREM. Although the results of his MSLT indicated
SOREM improvements compared to month 2, Henry continued to
exhibit clinically significant daytime sleepiness.
Henry did not endorse significant EDS on the modified ESS at
month 15 (ESS = 4; see Table 9.2). He did endorse increased con-
cern on the PedsQL MFS regarding fatigue across the general,
sleep/rest, and total fatigue domains. For example, Henry
endorsed that he “sometimes” felt tired, slept a lot, and spent a lot
of time in bed, and that he “often” felt too tired to spend time with
his friends. Henry’s mother continued to express significant con-
cerns regarding Henry’s fatigue. She endorsed concerns on simi-
lar items as she did in month 2, with the exception of her also
endorsing in month 15 that he “often” felt tired when waking up
in the morning.
Cognitive Testing
Behavioral Observations
During his research-based cognitive assessment prior to proton
therapy (month 2), Henry was described as exhibiting some lapses
in attention and motivation as well as frequent fidgeting, but he
otherwise appeared to be adequately engaged throughout testing.
He put forth strong effort throughout his cognitive testing in month
12, and he did not exhibit outward signs of inattention, distractibil-
ity, or impulsive behaviors. There were also no observable signs of
sleepiness (e.g., dozing off, “zoning out”). Henry displayed poor
speech articulation, and he frequently exhibited difficulties with
word finding and expressive language (i.e., poor coherence of sen-
tence construction and often talking around the point he was mak-
ing). He did not demonstrate difficulties following directions (i.e.,
receptive language). The results were thought to reflect valid esti-
mates of his functioning at the time of administration.
Intellectual Functioning
Henry was administered the Wechsler Intelligence Scale for
Children, 4th edition (WISC-IV) in month 2 during his baseline
research-based cognitive assessment. In month 12, given the
recent WISC-IV administration, Henry was administered the
Wechsler Abbreviated Scale of Intelligence, 2nd Edition
(WASI-II), as a brief re-assessment of cognitive functioning as
part of his clinical assessment. The results in months 2 and 12
indicated variable and generally underdeveloped cognitive abili-
ties. His performance fell 1.33 to 2.75 standard deviations (SDs)
below age-based norms across domains, including verbal reason-
ing, nonverbal reasoning, and working memory. Henry exhibited
a significant personal strength in his Average range processing
speed skills. During his month-15 research-based follow-up
assessment, Henry continued to exhibit impairments on verbal
reasoning and working memory tasks. He exhibited a significant
improvement in his performance on nonverbal reasoning tasks
(i.e., nearly 2 SD increase), which fell within expected age limits.
The variability between domains and across time points called
into question the stability of his cognitive functioning. See
Table 9.3 for results.
9 Brain Tumors 141
Table 9.3 Intellectual, verbal fluency, and academic functioning

Measure/scalea Month 2 Month 12b Month 15
WISC-IV/WASI-II
Full scale IQ 71 74 72
Verbal comprehension 71 58 71
Similarities (4) [22] (4)
Vocabulary (6) [27] (6)
Perceptual reasoning 73 – 100
Block design (7) – (10)
Matrix reasoning (4) [42] (10)
Working memory 71 – 65
Digit span (6) – (4)
Letter-number sequencing (4) – (4)
Processing speed 94 – 97
Coding (8) – (6)
Symbol search (10) – (13)
WJ-III cognitive
Retrieval fluency 70 – 84
WJ-III achievement
Math
Calculation 83 80 70
Applied problems – 69 -
Math fluency 79 81 80
Reading
Letter-word identification 83 78 88
Passage comprehension – 74 -
Reading fluency 66 78 81
a
Standard score, (scaled score), [T-score]
b
WASI-II administered
Academic Achievement
Henry was administered selected subtests of the Woodcock-
Johnson III Tests of Achievement to obtain an assessment of his
academic achievement in the domains of reading and mathematics.
His performance consistently fell below expected age and grade
limits across measures of reading and mathematics overall, with a
particular weakness in his calculation and applied math skills. His
performance was consistent across assessments (i.e., <1 SD differ-
ence), with the exception of his significantly increased perfor-
mance for reading fluency (i.e., 1 SD; see Table 9.3).
Verbal Fluency
On the Woodcock-Johnson Tests of Cognitive Abilities, 3rd Edition
(WJ-III Cognitive; see Table 9.3), Henry’s performance in month 2
fell within the low end of the Borderline range and below expected
age limits on a task assessing speeded retrieval of categorical and
verbal information. His performance was nearly 1 SD higher and
falling within the Low Average range during his month-15 follow-up
assessment.
Learning and Memory

On the California Verbal Learning Test, Children’s Version
(CVLT-C) administered in month 2, Henry displayed severe
impairments in his performance across trials and after both short
and long delays, as well as in his discrimination between learned
and new information. Henry was administered the Children’s
Memory Scale (CMS) during his month-12 clinical assessment to
re-assess his learning and memory across verbal and visual
domains. He continued to exhibit impairments (i.e., Borderline to
Very Low range), with variability between and within domains
(see Table 9.4). Henry appeared to have minimal benefit from rec-
ognition tasks (i.e., multiple choice) at either time point. He exhib-
ited a high number of false positives on these tasks, and only
approximately one-third of his errors were semantically or phone-
mically similar. Henry had relatively less difficulty with informa-
tion that was visual or less detailed and complex in nature.
Executive Functioning and Attention

During his research-based assessments (months 2 and 15), Henry
was administered the Delis-Kaplan Executive Function System
(DKEFS) Color-Word Interference subtest, and Henry’s mother
completed the Behavior Rating Inventory of Executive Function
(BRIEF) as objective and subjective assessments of Henry’s exec-
utive functioning, respectively (see Table 9.5). Henry was unable
to complete the executive functioning task (i.e., inhibition/switch-
ing) in month 2 due to his difficulty understanding the task, and his
performance in month 15 included a high number of errors (i.e., 10
total errors). Parent-proxy responses on the BRIEF in month 2
indicated clinically significant elevations on the working memory,
shifting, initiation, and monitoring subscales. More specifically,
9 Brain Tumors 143
Table 9.4 Assessment of verbal and visual learning/memory

Measure/scalea Month 2 Month 12
CVLT-C
List A Trial 1 [−2.5] –
List A Trial 5 [−2.5] –
List B free recall [−2.0] –
Short delay
Free recall [−2.5] –
Cued recall [−3.0] –
Long delay
Free recall [−1.5] –
Cued recall [−3.0] –
Delayed recognition
Correct recognition hits [0.0] –
False positives [4.5] –
Discriminability [−5.0] –
Children’s memory scale
Verbal memory (immediate) – 66
Verbal memory (delayed) – 60
Delayed recognition memory – 63
Stories
Immediate – (3)
Delayed – (2)
Delayed recognition – (6)
Word pairs
Immediate – (6)
Delayed – (5)
Delayed recognition – (2)
Visual memory (immediate) – 72
Visual memory (delayed) – 75
Dots
Immediate – (9)
Delayed – (8)
Faces
Immediate – (2)
Delayed – (4)
General memory – 56
a
Standard score, (scaled score), [Z-score]
Table 9.5 Objective and subjective measures of executive functioning

Measure/scalea Month 2 Month 15
DKEFS color-word interference
Color naming (12) (11)
Word reading (9) (9)
Inhibition (14) (12)
Errors (10) (10)
Inhibition/switching N/Ab (10)
Errors N/A (4)
BRIEF
Behavioral regulation index [56] [41]
Inhibit [44] [42]
Shift [67] [47]
Emotional control [58] [40]
Metacognition index [66] [55]
Initiate [75] [53]
Working memory [69] [67]
Plan/organize [56] [58]
Organization of materials [49] [42]
Monitor [69] [40]
Global executive composite [63] [49]
a
(Scaled score), [T-score]
b
N/A, Not applicable, as patient unable to complete
Henry struggled with initiating tasks, independently generating

ideas or engaging in flexible problem-solving strategies, switching
or alternating attention, checking his work, utilizing working
memory skills, displaying interpersonal awareness, and complet-
ing complex tasks. This was consistent with parent-reported con-
cerns during the clinical interview. During month 15, his mother’s
responses indicated a clinically significant elevation on the work-
ing memory subscale. She otherwise did not endorse significant
concerns across the remaining domains.
Adaptive Functioning
The Adaptive Behavioral Assessment System, 2nd Edition
(ABAS-II), was completed by Henry’s mother in month 2 as a
measure of his adaptive functioning. Her responses indicated that
9 Brain Tumors 145
Henry’s functioning was below expected age limits across the con-
ceptual, social, and global adaptive functioning composites
(Standard Score Range = 70–75). The exception to this was the
practical skills composite that fell within the Low Average range
(Standard Score = 85). Parent ratings indicated a relative strength
in health and safety skills (Scaled Score = 10) and relative weak-
nesses in social and self-direction skills (Scaled Scores = 3).
Subscale ratings otherwise ranged from Low Average (i.e., func-
tional academics, home living, self-care skills) to Borderline (i.e.,
communication, leisure, community use skills).
Diagnostic Impressions
Over the course of 15 months during treatment and follow-up for

craniopharyngioma, Henry’s symptoms of EDS increasingly inter-
fered with his functioning in the home and school settings. He fre-
quently fell asleep in school and typically took 2-h afternoon naps
despite adequate sleep with no reported difficulties with sleep
onset, maintenance, or timing. Thus, other possible explanations
for his EDS (i.e., insomnia, inadequate sleep, delayed sleep-wake
phase disorder) were ruled out. His baseline MSLT indicated that
he initiated sleep and experienced sleep onset REM (SOREM) at
each of the four nap opportunities. Henry did not exhibit SOREM
during his month 15 MSLT; however, he continued to exhibit short
sleep latency at each nap consistent with hypersomnolence. His
PSGs also revealed borderline to mild obstructive sleep apnea, but
his sleep medicine physician indicated that this was likely not a
contributing factor to his EDS. Henry was given a diagnosis of
Narcolepsy due to a Medical Condition without Cataplexy. This
was consistent with patient-reported concerns regarding EDS at
the beginning of medical treatment. Henry’s fatigue ratings in
month 2 and 15 were qualitatively consistent with or better than
healthy norms; while parent-proxy report indicated significant
fatigue across domains and time points that were qualitatively
poorer than both healthy and oncology norms. Because of Henry’s
lower performance on verbal comprehension measures, he may
have had difficulty in appropriately comprehending and respond-
ing to the fatigue questionnaires.
The results of psychological assessment indicated variable and

generally underdeveloped cognitive abilities, below grade level
academic performance, difficulties with word finding and expres-
sive language, executive dysfunction, and deficits in learning and
memory. His pattern of performance on language-based measures
may be attributed to the location of his tumor that included mass
effect on the hypothalamus and of his recurrent subdural hemato-
mas that included midline shift and distorted ventricles; however,
his most recent MRI indicated a decrease in size of the residual
tumor and resolution of the subdural collections and mass effect.
His vulnerability to poorer cognitive functioning may be attribut-
able to a combination of factors, including premorbid weaknesses
in cognitive functioning (e.g., developmental language delays), his
brain tumor, and emerging cognitive changes secondary to proton
therapy. Henry’s psychological assessment results were consistent
with other adolescents with craniopharyngioma who have been
shown to have deficits in executive functioning and attention. This
was likely further complicated by his narcolepsy. The specific etiol-
ogy of Henry’s learning and memory deficits was unknown, but
there were a number of factors that may have contributed to the
development and maintenance of these problems, including his his-
tory of a brain tumor, poorer executive functioning, and persistent
EDS. Henry met diagnostic criteria for Unspecified Mental Disorder
Due to Another Medical Condition because of his pattern of lower
cognitive functioning and its impact on his academic performance.
Management Chosen
Following Henry’s month-15 sleep study, his neurologist and radi-

ation oncologist initiated modafinil (50 mg QAM) due to persis-
tent concerns with hypersomnia on objective sleep testing and the
increased functional daytime impairment.
Clinical Course and Outcome
Henry’s MRI in month 21 indicated that his residual suprasellar

tumor was grossly stable (1.5 cm × 1.5 cm × 1 cm), with a small
extension to the midline inferiorly (4 mm × 3 mm). He exhibited a
9 Brain Tumors 147
slightly small pituitary gland, a deformed hypothalamus, mildly

enlarged third and lateral ventricles (unchanged), a mass effect
that mildly deformed the optic chiasm (i.e., intact vision), a grossly
stable surgical defect in the anterior corpus callosal body, and mild
encephalomalacia along the left frontal lobe that was likely sec-
ondary to surgery. His PET scan in month 21 revealed normalized
reuptake. Overall, Henry’s diagnostic imaging results were consis-
tent with his medical and surgical history. He continued to receive
growth hormone replacement and treatment for hypothyroidism
and adrenal insufficiency.
The results from Henry’s PSG and MSLT in month 21 (i.e., 6
months post-modafinil initiation) indicated significant improve-
ments compared to previous sleep studies (see Table 9.2). He
received an adequate and increased quantity of sleep during his
PSG (527.5 min), with a SOL of 9.0 min and sleep efficiency of
96.3%. The distribution of his sleep stages continued to include
a decreased proportion of REM sleep (i.e., 10.7%). Henry exhib-
ited 65 spontaneous arousals, none of which were associated
with respiratory arousals. There were improvements in his previ-
ously noted respiratory impairments, as his AHI was 0.2 events
per hour of sleep, which included no obstructive or central
apneas, one mixed apnea, and one hypopnea. Henry’s minimum
oxygen saturation (SpO2) was decreased (i.e., 86%), but the num-
ber of desaturations decreased (i.e., 13 desaturations). There con-
tinued to be no periodic limb movements. On the MSLT, Henry
again initiated sleep at each nap opportunity; however, his mean
sleep onset latency was improved (M = 15.0 min, Range = 8.5–
17.5 min), and there were no episodes of SOREM. His sleep phy-
sician recommended continued stimulant use given the
improvement in daytime sleepiness and SOREMs.
Consistent with MSLT findings, Henry did not endorse signifi-
cant EDS on the modified ESS at month 21 (ESS = 4; see
Table 9.2). He also endorsed decreased frequency of fatigue
symptoms since month 15 on the PedsQL MFS. Areas of relative
improvement (i.e., endorsing “never” rather than “sometimes or
“often”) included items related to feeling too tired to spend time
with friends, sleeping a lot, and spending a lot of time in bed.
Henry’s mother endorsed significant improvements in her con-
cerns regarding Henry’s fatigue since his initiation of modafinil.
She also indicated at medical follow-up significantly decreased
sleep problems and interference of daytime sleepiness on activi-

ties since initiating modafinil, as Henry was no longer taking day-
time naps or exhibiting EDS at home or school. He maintained a
full night’s sleep, with adequate sleep duration and no reported
difficulties with initiating sleep, sleep maintenance, or waking in
the morning.
The variability or changes in Henry’s performance during cog-
nitive testing were not consistent with the noted improvements in
his diagnostic imaging and indicated a lack of stability in his cog-
nitive functioning. This case example may highlight how vulnera-
ble patients with brain tumors, particularly craniopharyngioma,
can be from a morbidity perspective and how difficult it can be to
establish a true baseline of premorbid cognitive abilities. In
Henry’s case, pharmacological interventions such as stimulants
can be helpful in managing daytime alertness and related impair-
ment. This may not address his overall below average cognitive
performance, but it may optimize his current level of functioning.
Discussion
Craniopharyngiomas are low-grade intracranial tumors that

account for 6% of all pediatric brain tumors [2, 3]. Although the
5 year survival rate is greater than 90% [3], survivors of craniopha-
ryngioma frequently experience long-term morbidity, including
endocrinopathies, cognitive difficulties, and excessive daytime
sleepiness.
EDS is the most commonly reported sleep problem in children
and adolescents with cancer, with rates higher than those
observed in otherwise healthy obese adolescents [4–6]. EDS is
noted to include longer duration of sleep, daytime napping, sig-
nificant difficulty awakening in the morning, and/or difficulty
maintaining alertness during daytime activities [5, 7]. Although
they have excessive sleepiness, brain tumor survivors are not
likely to report symptoms of narcolepsy, such as cataplexy, hyp-
nagogic hallucinations, or sleep paralysis [8]. Approximately half
of pediatric oncology patients report fatigue and EDS, while up
to 80% of children and adolescents with brain tumors involving
9 Brain Tumors 149
the hypothalamus, thalamus, and brainstem experience signifi-

cant symptoms of daytime sleepiness [5, 9, 10]. Importantly,
greater extent of hypothalamic involvement of the tumor has
been associated with a higher likelihood of having objectively
documented hypersomnia in children and adolescents with cra-
niopharyngioma [9]. In adolescent survivors of brain tumors,
self-reported EDS is not well-recognized by parents [6], and they
describe impact of EDS on their academic functioning [8].
Furthermore, in a case series of three adolescent and young adult
patients with EDS who had been treated for craniopharyngioma
with surgery and radiation therapy, significant circadian disruption
was identified. In particular, both 24-h mean melatonin levels and
nighttime melatonin levels were markedly lower than historical
controls. In addition, although PSG demonstrated relatively stable
sleep architecture, circadian disruption was evident with higher
nighttime activity rates, lower daytime activity levels, and irregular
sleep routines [11]. This indicates that one potential significant
contributor to EDS is likely a disrupted circadian rhythm.
Symptoms of EDS are particularly important to attend to in
adolescents with brain tumors because sleep disturbances are
linked to a host of negative outcomes including difficulties with
physical and emotional health, academic performance, neurocog-
nitive function, immune function, and overall quality of life [12–
14]. In adolescent brain tumor patients and survivors, this is of
particular concern as sleep plays a crucial role in neural recovery
and tissue renewal [14, 15]. Healthy sleep also plays a crucial role
in many areas of cognitive functioning including memory, atten-
tion, and emotion regulation [16–19]. Even in healthy adolescents,
sleepiness is associated with more problematic executive function-
ing, which underlies many cognitive skills necessary for success-
ful academic performance [20]. Adolescents with brain tumors are
already at-risk for poor school performance from extended school
absences during treatment and neurocognitive late effects of can-
cer treatments [21–23], and excessive daytime sleepiness may
only compound this risk.
Henry’s case demonstrates the multitude of factors that can
impact adolescents with brain tumors both during and after treat-
ment. His craniopharyngioma was characterized by mental status
changes at the time of diagnosis with associated subdural hemato-

mas, enlarged ventricles, hypoperfusion of the left frontal region of
the brain, obstructive hydrocephalus, and midline shift with mass
effect on the hypothalamus. Although the hematomas resolved and
his brain perfusion improved, Henry continued to demonstrate
commonly observed difficulties following diagnosis and treatment
for a craniopharyngioma, particularly with hypothalamic involve-
ment, including endocrinopathies, excessive daytime sleepiness,
and cognitive and academic difficulties. While Henry and his
mother initially denied a history of sleep problems, hypersomnia
quickly was recognized with MSLT. Over time, his sleepiness
began to have a significantly negative impact on his functioning
both at home and at school. With the use of modafinil, Henry’s
objectively documented sleepiness, quality of life, and ability to
engage in appropriate daytime activities improved remarkably. It is
important to note, however, that with almost one third of a case
series of children with craniopharyngioma having QTc prolonga-
tion, all craniopharyngioma patients and survivors who are treated
with psychostimulants should be monitored with regular electro-
cardiograms [24]. This case highlights the importance of objec-
tively evaluating sleepiness in adolescents with brain tumors
(particularly those involving the hypothalamus), the importance of
closely monitoring cognitive and academic performance, and the
important role of medication management in impacting daytime
functioning in this vulnerable population.
Clinical Pearls/Pitfalls
• Children and adolescents with brain tumors, particularly those

of central location such as craniopharyngioma, are at risk for
excessive daytime sleepiness.
• Youth with brain tumors are also at risk for cognitive and aca-
demic difficulties.
• Vulnerability to cognitive and academic difficulties coupled
with excessive daytime sleepiness can result in children who
fall increasingly behind at school and suffer from ongoing
problems at home.
9 Brain Tumors 151
• Both nighttime and daytime sleep should be carefully moni-

tored in youth who have been diagnosed with centrally located
brain tumors.
• Without intervention, symptoms of excessive daytime sleepi-
ness and related daytime impairment are not likely to indepen-
dently resolve with time and, in fact, may worsen.
• Excessive daytime sleepiness can be improved with the use of
stimulants, such as modafinil.
• Improvements in alertness can also contribute to improved
symptoms of daytime fatigue and attention and have additional
benefit on improved quality of life.
Learning Points
• All children and adolescents with centrally located brain tumors

should have a PSG and MSLT to rule out a diagnosis of hyper-
somnia or narcolepsy, with careful monitoring over the course
of treatment and survivorship. The assessment should rule-out
other contributors of the excessive daytime sleepiness present
(e.g., insufficient sleep, sleep-related breathing disorders, and
circadian rhythm disorders).
• Hypersomnia in pediatric brain tumors should be adequately
treated, and psychostimulants, such as modafinil, should be
considered when treating daytime sleepiness.
• Patients should be encouraged to engage in good sleep hygiene
and establish regular sleep/wake schedules with adequate sleep
duration.
• Neuropsychological or psychological assessments may be nec-
essary to monitor and address daytime impairment.
References
1. Kukal K, Dobrovoljac M, Boltshauser E, Ammann RA, Grotzer MA. Does
diagnostic delay result in decreased survival in paediatric brain tumours?
Eur J Pediatr. 2009;168(3):303–10.
2. Garre ML, Cama A. Craniopharyngioma: modern concepts in pathogene-
sis and treatment. Curr Opin Pediatr. 2007;19(4):471–9.
3. NCI. Childhood craniopharyngioma treatment. 2015. http://www.cancer.

gov/types/brain/hp/child-cranio-treatment-pdq.
4. O’Gorman CS, Simoneau-Roy J, Pencharz P, MacFarlane J, MacLusky I,
Narang I, et al. Sleep-disordered breathing is increased in obese adoles-
cents with craniopharyngioma compared with obese controls. J Clin
Endocrinol Metab. 2010;95(5):2211–8.
5. Rosen GM, Bendel AE, Neglia JP, Moertel CL, Mahowald M. Sleep in
children with neoplasms of the central nervous system: case review of 14
children. Pediatrics. 2003;112(1 Pt 1):e46–54.
6. Brimeyer C, Adams L, Zhu L, Srivastava DK, Wise M, Hudson MM, et al.
Sleep complaints in survivors of pediatric brain tumors. Support Care
Cancer. 2016;24(1):23–31.
7. Rosen GM, Shor AC, Geller TJ. Sleep in children with cancer. Curr Opin
Pediatr. 2008;20(6):676–81.
8. Crabtree VM. Sleep in children with cancer and other chronic diseases. In:
Kushida CA, editor. The encyclopedia of sleep. Waltham, MA: Academic;
2013. p. 632–3.
9. Jacola L, Conklin H, Scoggins M, Ashford J, Merchant T, Mandrell B,
et al. Investigating the role of hypothalamic tumor involvement in sleep
and neurocognitive outcomes among children treated for craniopharyngi-
oma. J Pediatr Psychol. 2016;41(6):610–22.
10. Kaleyias J, Manley P, Kothare SV. Sleep disorders in children with cancer.
Semin Pediatr Neurol. 2012;19(1):25–34.
11. Lipton J, Megerian JT, Kothare SV, Cho YJ, Shanahan T, Chart H, et al.
Melatonin deficiency and disrupted circadian rhythms in pediatric survi-
vors of craniopharyngioma. Neurology. 2009;73(4):323–5.
12. Beebe DW. Neural and neurobehavioral dysfunction in children with
obstructive sleep apnea. PLoS Med. 2006;3(8), e323.
13. Donaldson DL, Owens J. Sleep and sleep problems. In: Bear GG, Minke
KM, editors. Children’s needs III: development, prevention, and interven-
tion. Washington, DC: National Association of School Psychologists;
2006. p. 1025–39.
14. Mandrell BN, Wise M, Schoumacher RA, Pritchard M, West N, Ness KK,
et al. Excessive daytime sleepiness and sleep-disordered breathing distur-
bances in survivors of childhood central nervous system tumors. Pediatr
Blood Cancer. 2012;58(5):746–51.
15. Clanton NR, Klosky JL, Li C, Jain N, Srivastava DK, Mulrooney D, et al.
Fatigue, vitality, sleep, and neurocognitive functioning in adult survivors
of childhood cancer: a report from the childhood cancer survivor study.
Cancer. 2011;117(11):2559–68.
16. Astill RG, Van der Heijden KB, Van Ijzendoorn MH, Van Someren
EJ. Sleep, cognition, and behavioral problems in school-age children: a
century of research meta-analyzed. Psychol Bull. 2012;138(6):1109–38.
17. Born J, Wilhelm I. System consolidation of memory during sleep.
Psychological Research. 2012;76(2):192–203.
9 Brain Tumors 153
18. Walker MP, van der Helm E. Overnight therapy? The role of sleep in
emotional brain processing. Psychol Bull. 2009;135(5):731–48.
19. Weissman DH, Roberts KC, Visscher KM, Woldorff MG. The neural
bases of momentary lapses in attention. Nat Neurosci. 2006;9(7):971–8.
20. Anderson B, Storfer-Isser A, Taylor HG, Rosen CL, Redline S.
Associations of executive function with sleepiness and sleep duration in
adolescents. Pediatrics. 2009;123(4):e701–7.
21. Daly BP, Brown RT. Scholarly literature review: management of neuro-
cognitive late effects with stimulant medication. J Pediatr Psychol.
2007;32(9):1111–26.
22. Moore 3rd BD. Neurocognitive outcomes in survivors of childhood
cancer. J Pediatr Psychol. 2005;30(1):51–63.
23. Spencer J. The role of cognitive remediation in childhood cancer survivors
experiencing neurocognitive late effects. J Pediatr Oncol Nurs. 2006;
23(6):321–5.
24. Mong S, Pomeroy SL, Cecchin F, Juraszek A, Alexander ME. Cardiac risk
after craniopharyngioma therapy. Pediatr Neurol. 2008;38(4):256–60.
Insomnia
10
Mariya Narizhnaya and Matthew R. Ebben
Clinical Case
The case we will present is a 19 years old female college student

who lives on campus and shares a room with three roommates. She
complains of tiredness and trouble concentrating in class. She also
reports difficulty initiating sleep, frequent awakenings throughout
the night as well as early morning arousals with the inability to
quickly fall back to sleep.
Currently, she attends classes from 8:00 am to 3:00 pm and
reports having one cup of coffee in the morning. On days that she
needs to study for a test, she may have more coffee or energy
drinks throughout the day. After class, she attends mandatory dor-
mitory activities, studies, or participates in social activities with
her friends. Occasionally, the patient naps for several hours after
class. Her roommates are respectful of her sleep schedule, mean-
ing they turn off their lights and end their phone conversations
around 11:00 pm.
M. Narizhnaya, M.A. (*) • M.R. Ebben, Ph.D.

Department of Neurology, Weill Cornell Medical College,
425 East 61st St., New York, NY 10065, USA
e-mail: narizhnay@hartford.edu; mae2001@med.cornell.edu

156 M. Narizhnaya and M.R. Ebben
Physical Exam
The young woman was oriented to person, place, and time and is
of average height and weight. No abnormal movements were pres-
ent, and her posture and gait appeared normal. She is not suicidal,
homicidal, and did not display evidence of a thought disorder, or
serious psychopathology. She denies any substance abuse, medical
illnesses, history of trauma, or previous hospitalizations.
The patient’s general physical evaluation showed that she was
healthy. She did not appear to be in acute distress. Her vital signs
were within normal limits for her age. However, she yawned fre-
quently during the intake session and reported that she was suffer-
ing from excessive sleepiness and lack of energy. An evaluation of
her current lifestyle and daily habits, which was designed to iden-
tify behaviors and thought patterns that might contribute to her
sleep problems, indicated that she experiences situational distress
and does not possess coping skills to deal with this stress appropri-
ately. She stated that she thought that sleep was stressful and ter-
rible because of the pressure she experienced to fall asleep. She
also worried about not being able to sleep enough or not falling
asleep quickly at bedtime and negative effects of lack of sleep on
her daily functioning and performance in class.
Diagnostic Interview
During her first session, the patient was asked open-ended questions
about her presenting sleep problem. She began having trouble
sleeping at 17 years old. She remembers lying in bed and experienc-
ing worrisome thoughts about her performance on a math test. She
felt overwhelmed with her school work and lay in bed for hours, not
feeling tired. At the time of the initial consultation, the patient con-
tinued to experience worrisome thoughts at bedtime about the next
day and the effects of her insufficient sleep on her school work. She
frequently used her smartphone in bed to text her friends and peruse
social media websites. She experienced difficulty falling asleep
every night. She denied previous treatment for her sleep problems.
Often, she felt that she would never find relief from her sleep trou-
ble and needed to learn to function on limited sleep quantity.
10 Insomnia 157
The patient never considered taking medication to help her fall

asleep and is not interested in trying them. When she is tired at
school or needs to study, she has coffee or an energy drink. On days
that she does not need to study, she takes a nap from 5:00–6:00 pm.
She reported that the most significant effect of her lack of sleep is
being too tired to pay attention in her classes and not having enough
energy to do her homework. It is particularly burdensome for her to
study for tests. Because she is too tired to concentrate, she feels
frustrated and needs to read the material over and over.
When she was asked how she handles her inability to sleep at
bedtime, she reported that she stays in bed and tries to find a more
comfortable position. During the week, she usually goes to bed at
midnight, but on nights before tests, she may study until 2:00 am.
As a rule, she gets into bed with her smartphone, texts her friends,
and reviews social media pages for about an hour. She believes that
she has difficulty falling asleep due to her inability to stop thinking.
Typically, she is worried about her performance the next day. Her
thoughts sometimes wonder to her chores, tests, and relationships.
She is often concerned both about not sleeping at night and that the
next day, she will be tired during her classes. On many nights, she
can toss and turn in bed until 3:00 am, constantly looking at her
alarm clock and worrying that she will not be able to function dur-
ing the next day. She finally falls asleep around 3:00 am, but wakes
up every hour. She is able to fall back to sleep fairly quickly, after
checking the time on her phone. Frequently, she wakes up around
5:00 am and is unable to go back to sleep. Upon arousing, she feels
anxious and tired, but gets out of bed around 5:30 am to start her
day. On weekends, she may go to sleep as late as 4:00 am due to
social activities in the dorm. On most weekend nights, she does not
report worrisome thoughts about her ability to function the next
day. Nonetheless, even on weekends, she has several arousals dur-
ing the night. She may wake up around 7:00 am, stay in bed, and
fall back to sleep until 10:00 am. On both weekdays and weekends,
she indicates that she does not sleep well.
The patient complains of dissatisfaction with sleep quality and
quantity characterized by difficulty initiating (e.g., she reported
lying in bed for hours and not being able to fall asleep) and main-
taining sleep (e.g., she wakes up every hour and is not able to fall
back to sleep right away). In addition, although she does report that
her inability to fall asleep at bedtime is associated with not feeling

tired due her schedule, she has an irregular sleep schedule, and at
times, she takes naps during the day. She indicates that she is ready
to go to sleep and feels exhausted at bedtime, but cannot fall asleep
due to her inability to stop thinking. In addition, she does not have
difficulty waking up in the morning. She reports experiencing
sleep problems, which occur 4–5 times during the week, for about
2 years. She also complains of difficulties concentrating during her
classes and homework associated with the lack of sleep. Therefore,
the patient presents an irregular sleep/wake disorder with elements
of insomnia. The patient’s difficulties with concentrating on tests
may be explained by lack of sleep as well as frequent caffeine
consumption throughout the day, on days that she has tests.
Management Chosen
The young woman attended 6 weekly sessions of cognitive behav-

ioral therapy for insomnia (CBT-I). In order to understand the
patient’s sleep pattern over time, she was provided with a sleep log.
In the sleep log, she was advised to note the time she got into bed,
the time she fell asleep, as well as the time she took naps, had caf-
feine, took medication, and exercised. Her sleep patterns were
determined from the first week of the sleep log (see sleep log 1,
week 1 (Fig. 10.1)); her average total sleep time was calculated to
be about 6 h. Therefore, she was recommended a sleep restriction
schedule of 6 h of sleep. She was advised to go to bed no earlier
than 12:00 am and wake up no later than 6:00 am. However, she
was allowed to go to sleep later than 12:00 am or wake up earlier
than 6:00 am. It was also recommended to stop napping and elimi-
nate caffeine intake after 12:00 pm. In order to abstain from nap-
ping after classes, when she felt sleepy in her dorm, she was
encouraged to get up and walk around. She also enlisted the help
of her roommates. They promised to support her during treatment
and prevent her from napping during the day. During the third
week of treatment, the patient complained that she was feeling
frustrated due to lying in bed for several hours prior to initiating
sleep on Saturday and after an arousal on Sunday (see sleep log 2,
week 3 (Fig. 10.2)). She was encouraged to only get into bed when
10 Insomnia 159
Fig. 10.1 Sleep log 1

she felt tired and explained that the bed should only be used for
sleep or physical intimacy. If she did not feel sleepy while lying in
bed, she was recommended to get out of bed and perform relaxing
activities. The patient identified drawing and reading as calming.
Therefore, she was encouraged to perform those activities at her
desk instead of lying in bed and forcing herself to go to sleep. This
was recommended to help her form a positive association between
her bed and sleep.
A part of her nighttime regiment was getting into bed with her
smartphone. While in bed, she spent several hours texting, talking
on the phone, and visiting social media sites. Due to the stimulat-
ing social content as well as the potential effect of short wave blue
light emitting from this device on her melatonin levels and circa-
dian rhythms these activities prolonged her bedtime. Because
communicating with her friends was exciting and physically
arousing, she would not feel tired for several hours after the con-
versations were done. Therefore, she was advised to refrain from
going to bed with her smartphone. Removing the arousing and
emotionally and physiologically engaging stimulus from her bed-
time routine was recommended to help her relax.
Because the negative thoughts associated with sleep caused her
frustration at bedtime, cognitive restructuring was introduced. This
patient’s negative beliefs were identified with open-ended ques-
tions about her thoughts and feelings about sleep. Clinicians may
also utilize the Dysfunctional Beliefs and Attitudes about Sleep
(DBAS-16) [1] questionnaire, which is a tool that is often used to
assess dysfunctional beliefs about sleep. The patient was encour-
aged to begin to recognizing her negative thoughts associated with
sleep and bedtime. Some of the thoughts that she reported included,
“falling asleep is stressful and I’m not good at it,” “I will lie in bed
for hours,” “I will not be able to study for my test tomorrow because
I cannot sleep long enough.” Once the thoughts were identified, she
was taught the connection between her thoughts and their impact
on emotional and physiological arousal. Because her negative
thoughts about sleep contribute to emotional arousal and produce
anxiety at bedtime, she was encouraged to change her beliefs about
sleep from thoughts that induced feelings of stress, such as “I am
going to sleep right now,” to thoughts that would help her relax,
such as “I am going to lie in my bed and rest.” She was also taught
10 Insomnia 161
to change her negative thoughts about sleep: “falling asleep is

stressful” to positive thoughts “falling asleep is relaxing and com-
forting.” In addition, her irrational beliefs associated with popular
myths about most people needing 8 h of sleep to function during
the day were challenged. The patient was explained that the recom-
mended amount of sleep follows a normal distribution, with some
people needing more than 8 h and other needing less than 8 h. To
help her understand the amount of time that she needs to sleep, she
was shown her sleep log. The sleep log from the first week exhib-
ited that her average sleep time was 6 h. Therefore, she was
explained that for her, 6 h is a sufficient sleep amount.
To help the patient relax at bedtime and begin to gain control
over her fleeting thoughts, she was taught visual imagery
(Table 10.1). The patient was advised to think of a story, in which
she had to be the only character and needed to pay attention to
every single detail. In addition, the story needed to have a begin-
ning, middle, and an end. This technique was recommended to
help her to gain control over her mind–body relationship. The
patient was learning to recognize the effect of her worrisome
thoughts about daily stressors on her physiological parameters.
She noticed that as she was thinking about her test performance,
her heart rate became more rapid. She began using the technique
and reported that it provided a way to manage her never-ending
thinking process and de-escalated her heart rate.
In the beginning of every session, the patient and I reviewed her
sleep log from the previous week. In doing so, she could see the
impact of napping on her sleep routine. With the support of her
roommates, she was able to refrain from napping. Initially, the
patient complained of difficulty functioning due to feeling more
irritable and less focused during her studies. She was encouraged
to continue adhering to her sleep restriction schedule and explained
that these experiences are a normal part of treatment. The patient
reported experiencing stress prior to bedtime associated with poor
performance on a test she had recently taken. She also indicated
that she began experiencing worrisome thoughts about her future
and career. These thoughts kept her up until 5:00 am. On this night,
she was too upset to use cognitive restructuring and visual imag-
ery. In order to gain control over her stress, which may have exac-
erbated her physiological arousal, she was taught diaphragmatic
Table 10.1 Visual imagery and diaphragmatic breathing techniques, benefit, and description
162
Technique Benefit Description

Visual imagery This relaxation The patient is advised to lie down in bed, close his/her eyes, and think of a story that
technique uses has a beginning, a middle, and an end. He/she has to visualize every detail and must be
imagination to gain the only character in the story
control of worrisome
For example, I am going to a vacation to my beach house. I will need to pack. So, I
thoughts and allow
take my suitcase out of my close and put it on the floor. I unzip it. Then I take out a
the body to relax
shirt from my dresser drawer. I fold the shirt and place it in the suitcase
Diaphragmatic This relaxation The patient is advised to perform this technique at bedtime to help with relaxation. He/
breathing technique helps the she is instructed to place one hand on the chest and the other on the abdomen. When
body achieve a he/she takes a deep breath in, the hand on the abdomen should rise higher than the one
breathing rate that is on the chest. This insures that the diaphragm is pulling air into the bases of the lungs
associated with being
in a calm state After exhaling through the mouth, take a slow deep breath in through the nose
imagining that one is sucking in all the air in the room and hold it for a count of 7 (or
as long as one is able, not exceeding 7)
Slowly exhale through the mouth for a count of 8. As all the air is released with relaxation,
gently contract the abdominal muscles to completely evacuate the remaining air from the
lungs. It is important to remember that we deepen respirations not by inhaling more air but
through completely exhaling it
Repeat the cycle four more times for a total of 5 deep breaths and try to breathe at a
rate of one breath every 10 s (or 6 breaths per minute). At this rate our heart rate
variability increases which has a positive effect on cardiac health
M. Narizhnaya and M.R. Ebben
10 Insomnia 163
Table 10.2 Cognitive restructuring

The patient should Restructured thoughts
Automatic thoughts ask him/herself
Sleep is terrible What is a more Sleep is calming
positive thought?
I don’t like sleeping What is a more I like resting
positive thought?
Sleep is uncomfortable What is a more resting is relaxing
positive thought?
I feel pressure and stress What is a more I feel relaxed when I
when I think of sleep positive thought? think about dreaming
I am bad at sleeping What is a more I am good at resting
positive thought?
I will lie in bed for hours What is a more I am going to rest tonight
positive thought?
I need 8 h of sleep, or I What is a more My sleep log shows that
will not be able to pay realistic thought? I usually sleep for 6 h
attention in class
If I do not sleep, I will not What is a more I may be tired, but I will
be able to focus tomorrow realistic thought? get through my classes
breathing exercises (Table 10.1). She was also reminded that cog-
nitive restructuring and visual imagery have worked for her in the
past and that she should try to rely on these techniques even more
during stressful time periods.
The patient reported that using cognitive restructuring
(Table 10.2) aided her in gaining control over her stressful thoughts
at bedtime. She was successful at sleep restriction during the
school week, being able to sleep 6 h on most nights, with one or
two short awakenings. It was more challenging for the patient to
follow her sleep schedule during the weekends. She was engaged
in social activities with her friends and did not go to bed until
4:00 am. She reported being unable to wake up at 6:00 am because
she would not be able to study on this limited amount of sleep. She
also expressed that she could not get out of bed when her alarm
clock rang. She kept falling asleep and pressing the snooze bottom
until 8:00 am. However, showing her the impact her weekend sleep
schedule (e.g., bedtime of 4:00 am and morning awakening of
10:00 am) (see sleep log 3, week 5 (Fig. 10.3)) had on her daytime
functioning on Monday, motivated her to adhere to her designed
bedtime schedule. Despite her attempts, she has not been able to
maintain her sleep restriction schedule on weekends. She realizes

that waking up at 6:00 am on weekends is important to her treat-
ment, but has not been able to do so.
The patient reported improvement in initiation, maintenance,
and quality of sleep during the night. During treatment, she was
successful in eliminating naps and caffeine consumption from her
daily routine. She learned to identify the connection between her
thoughts, emotional experiences, and physiological reactions. The
patient may occasionally stay up to study later than 12:00 am, but
she adheres to her morning awakening time of 6:00 am most of her
time during the week. She indicated being able to concentrate bet-
ter in classes and reported improvement in daytime functioning.
Discussion
The 19 years old patient in this case study represents a typical

presentation of insomnia, which can be a significant problem for
adolescents. However, this population is least likely to seek help
10 Insomnia 165
[2]. Patients often report feeling tired during the day and can have
difficulty concentrating in class. Common complaints include
stress associated with bedtime, difficulty initiating sleep, frequent
and prolonged arousals during the night, and early morning awak-
enings, with the inability to go back to sleep. The individual dis-
cussed in this case study suffered from an irregular sleep schedule
marked by sporadic napping and a lack of a consistent bedtime,
inability to fall asleep at bedtime or following an early morning
arousal as well as frequent and long awakenings during the night.
She often worried that her daytime functioning would be nega-
tively impacted by her lack of sleep.
Undiagnosed and untreated insomnia can result in excessive
daytime sleepiness, irritability, difficulty concentrating, and poor
academic performance. Fatigue and inability to focus on school
work may not warrant concerns for adolescents. They may not be
aware that they are struggling with a sleep disorder. Therefore,
practitioners are encouraged to enquire about the adolescent’s sleep
when clinically indicated. Once insomnia has been diagnosed, an
individualized treatment plan should be designed, taking into
account the patient’s sleep schedule.
In order to formulate an appropriate treatment plan for an
insomniac, it is essential to properly diagnose the disorder. Sleep
problems can be associated with several factors, including sleep
hygiene problems (e.g., varied sleep schedule, frequent napping,
and emotionally and physically stimulating activities close to bed-
time). It should be noted that there are several sleep disorders, such
as delayed sleep phase (e.g., sleep disturbance due to changes to
the circadian rhythm), sleep disordered breathing, and movement
disorders, (e.g., restless legs or REM behavior disorder) as well as
psychiatric disorders (e.g., anxiety, depression, and attention defi-
cit hyperactivity disorder) that may cause individuals to have
symptoms that are similar to insomnia. In addition, family or
school pressure, and acute infection disease, or chronic disease
may also have a negative effect on sleep [3, 4]. Therefore, a practi-
tioner is advised to carefully evaluate the patient’s presenting prob-
lem. After thorough assessment, which includes open-ended
questions about sleep problems, bedtime and daytime regiment,
caffeine and medication use, and origin of the presenting problem,
a patient may be diagnosed with insomnia. Using a sleep log to
track sleep schedule, caffeine consumption, and medication usage

over time can help both make the diagnosis of insomnia and formu-
late the treatment plan.
Understanding insomnia though the 3P model can enlighten
both the patient and practitioner about the development and persis-
tence of this condition. This model describes three phases in the
development of persistent difficulty sleeping. These include pre-
disposing, precipitating, and perpetuating factors [5]. Predisposing
characteristics are temperament and personality traits, making a
patient more or less prone to hyperarousal. Individuals who are
more likely to have hyperarousals are more susceptible to develop-
ing the disorder [6]. Adolescent patients with insomnia tend to be
more prone to hyperarousal when compared with healthy controls
[7]. An individual’s sleep problems are further exacerbated by pre-
cipitating factors such as school-related stress [8]. The patient
reported that since she was 17 years old, she experienced stress
prior to bedtime associated with academic performance. Some
patients may think that in order to improve their sleep problems
that were worsened by a precipitating factor, such as school stress,
they may need to increase the time spent in bed to obtain the neces-
sary amount of sleep [8]. However, this behavior may become a
habit and exacerbate the patient’s insomnia after the precipitating
event has been resolved. The perpetuating habits, such as staying
in bed longer than needed and spending a majority of that time on
the internet or watching television close to bedtime, may attribute
to development of chronic insomnia [9]. Patients are advised to get
out of bed if they are not feeling sleepy and refrain from activities
that are not associated with sleeping.
While some individuals may find it comforting to use electronic
devices, such as smartphones and its immediate access to social
media when they are lying in bed, this habit may have a negative
effect on adolescents’ sleep [10]. Electronic media usage in ado-
lescents has been linked to delayed bedtime, long sleep onset, and
short sleep duration [11]. When adolescents visit social media sites
prior to sleep, they may experience psychophysiological arousal,
which is likely to prolong their bedtime. Adolescents indicated that
using electronic devices during bedtime was associated with poor
sleep quality [10]. In addition, electronic devices emit short wave-
length blue light. Continued exposure to blue light at bedtime may
10 Insomnia 167
lead to modification of circadian rhythms and impact the neurobe-

havioral function of sleep [12]. More specifically, the emitting blue
light may delay the circadian rhythm and inhibit levels of the
sleep-promoting hormone melatonin. Melatonin is a hormone that
is regulated by the central nervous system and secreted by the
pineal gland under dim light condition, approximately 2 h before
sleep onset [13]. It promotes sleep as well as has a role in regulat-
ing the circadian rhythms and body temperature. Melatonin sup-
pression is thought to promote wakefulness and increase alertness,
leading to a delayed bedtime as well as decreased alertness the
next morning [14]. Because the habit of using electronic devices
may prolong a patient’s bedtime and attribute to neurobiological
changes, they should be discontinued at least 1 h before bedtime.
Another recommended change to the patient’s daily habits was
eliminating napping during the day. The 2-process model of sleep-
wake regulation, which includes process C, or circadian system and
process S, or a homeostatic sleep drive, provides an explanation
about the detrimental effect of napping on a patient’s nighttime
sleep [15]. Process C refers to the collections of physiological
rhythms, with a cycle length of about 24-h that are driven by the
suprachiasmatic nucleus of the hypothalamus. Process S builds up
throughout the waking day and promotes sleep, while process C
promotes alertness. Sleep begins in late evening due to process
S. Once the homeostatic drive has been mostly reduced in the begin-
ning of a sleep cycle, the sleep period continues due to the declining
influence of the alerting function of circadian rhythm [16]. In indi-
viduals who do not experience sleep problems, process C and pro-
cess S are synchronized and sleep is relatively uninterrupted [9].
Studies show that buildup of delta pressure throughout the wak-
ing day appears to be weaker in patients with insomnia compared
to normal controls [16]. When individuals nap during the day, pro-
cess S during nighttime sleep may be affected by reducing delta
drive too early in the night [9]. This is likely to cause process S to
end prematurely, while process C is promoting alertness, leading
to a prolonged awakening in the middle of the night [9]. The
patient reported that she can initiate sleep quickly during a nap.
She wakes up from the nap and then is unable to go to sleep until
3:00 am, but easily wakes up at 6:00 am. According to the 2-pro-
cess model, she is having problems mounting sufficient process S.
The appropriate treatment for problems with process S is Cognitive

behavioral therapy for insomnia (CBT-I) for insomnia [9].
CBT-I, which includes techniques, such as sleep restriction,
cognitive restructuring, stimulus control, and relaxation tech-
niques (e.g., deep breathing and guided imagery), has been shown
to improve sleep as well as daytime fatigue in adolescents and col-
lege students [2, 17–19]. The patient was able to follow cognitive
and relaxation techniques and reported that her sleep initiation,
quality, and maintenance improved. Although, initially the patient
had difficulty adhering to these techniques when she experienced
excessive stress, with redirection and reminders that the techniques
have worked previously, she was able to continue using them and
reported significant improvement in her nighttime sleep and day-
time functioning.
When treating insomnia in adolescent patients with CBT-I, it is
recommended to help them to understand the importance of adher-
ing to the sleep restriction schedule and eliminating napping.
Practitioners should be aware that social life and academic needs
may affect compliance with the sleep schedule. Therefore, it is
important to review the weekly sleep log with the patient to help
illuminate the effect that deviating from the designed schedule has
on sleep. During the initial phases of treatment, patients may
require additional support, due to the effects of sleep deprivation.
Moreover, in some cases, their daytime functioning may be com-
promised. Therefore, it is important to warn patients that their
focus may be affected in the first few weeks of treatment, until the
sleep quality begins to improve.
Clinical Pearls/Pitfalls
• When working with adolescents, practitioners are encouraged

to inquire about the patient’s sleep.
• In diagnosing the patient’s insomnia, it is essential to differenti-
ate insomnia from other medical and psychiatric disorders
which include symptoms of sleep disturbance.
• A sleep log is an effective tool to use with patients because it
provides a visual aid to help them to understand how changes in
behavior affect their sleep quality.
10 Insomnia 169
• Adhering to the scheduled wake time is critical to improving

sleep quality in many individuals.
• In order to improve sleep quality, patients are advised not to nap
during the day.
• Avoid caffeine after 12:00 pm.
• Implementing CBT-I with adolescents can be challenging due
to difficulty maintaining a restricted sleep schedule. Practitioners
should expect that during the initial phases of treatment, the
patient may experience problems associated with daytime tired-
ness/sleepiness.
• Socially and physiologically stimulating activities, such as
using social media, texting, and talking on the phone, should be
eliminated from the patient’s bedtime regiment.
Learning Points
• Diagnostic interview with open-ended questions that assess all

factors (e.g., situational stress, behavioral, medical, social, and
emotional components) contributing to the sleep disturbance is
essential in diagnosing insomnia in adolescents. Careful assess-
ment will help the clinician to distinguish between insomnia
and problems related to medical, psychiatric, and/or other
sleep-related illness.
• A vital component to assessing patients’ sleep patterns is a
sleep log. Information from the sleep log allows the clinician to
understand the patient’s sleep patterns and total sleep time in
order to construct a therapeutic sleep schedule.
• Factors such as caffeine intake after 12:00 pm, naps, electronic
device usage at bedtime, spending too much time in bed as well
as negative cognitions and irrational beliefs can exacerbate
insomnia in adolescents. Patients are encouraged to maintain a
consistent sleep schedule, eliminate naps, restrict caffeine
intake to before 12:00 pm, and not use electronic devices while
in bed. In addition, cognitive restructuring and relaxation tech-
niques are recommended to help patients gain control over the
mind–body relationship.
References
1. Morin CM, Vallières A, Ivers H. Dysfunctional beliefs and attitudes about
sleep (DBAS): validation of a brief version (DBAS-16). Sleep. 2007;
30(11):1547–54.
2. de Bruin EJ, Bögels SM, Oort FJ, Meijer AM. Efficacy of cognitive
behavioral therapy for insomnia in adolescents: a randomized controlled
trial with internet therapy, group therapy and a waiting list condition.
Sleep. 2015;38(12):1913–26.
3. Kloss JD, Nash CO, Horsey SE. The delivery of behavioral sleep medi-
cine to college students. J Adolesc Health. 2011;48(6):553–61.
4. Nunes ML, Bruni O. Insomnia in childhood and adolescence: clinical
aspects, diagnosis, and therapeutic approach. J Pediatr (Rio J). 2015;91:
S26–35.
5. Spielman A, Yang CM, Glovinsky PB. Assessment techniques for insom-
nia. In: Kryger M, Roth T, Dement WC, editors. Principles and practice of
sleep medicine. Philadelphia: WB Saunders; 2011. p. 1631–45.
6. Drake C, Richardson G, Roehrs T. Vulnerability to stress-related sleep
disturbance and hyperarousal. Sleep. 2004;27(2):285–91.
7. Fernandez-Mendoza J, Li Y, Vgontzas AN, Fang J, Gaines J, Calhoun SL,
Liao D, Bixler EO. Insomnia is associated with cortical hyperarousal as
early as adolescence. Sleep. 2016;39(5):1029–36. pii: sp-00549-15.
8. Bastien CH, Vallieres A, Morin CM. Precipitating factors of insomnia.
Behav Sleep Med. 2004;2(1):50–62.
9. Ebben MR, Spielman AJ. A practical guide to insomnia assessment. In:
Pagel JF, Pandi-Perumal SR, editors. Primary care sleep medicine: a prac-
tical guide, vol. 55. New York: Springer; 2014. doi:10.1007/978-1-
4939-1185-1_6.
10. Polos PG, Bhat S, Gupta D, O’Malley RJ, DeBari VA, Upadhyay H,
Chaudhry S, Nimma A, Pinto-Zipp G, Chokroverty S. The impact of sleep
time-related information and communication technology (STRICT) on
sleep patterns and daytime functioning in American adolescents.
J Adolesc. 2015;44:232–44.
11. Hysing M, Pallesen S, Stormark KM, et al. Sleep and use of electronic
devices in adolescence: results form a large population-based study. BMJ
Open. 2015;5, e006748. doi:10.1136/bmjopen-2014-006748.
12. Cajochen C, Frey S, Anders D, et al. Evening exposure to a light-emitting
diodes (LED)-backlit computer screen affects circadian physiology and
cognitive performance. J Appl Physiol. 2011;110(5):1432–8.
13. Zhu L, Zee PC. Circadian rhythm sleep disorders. Neurol Clin.
2012;30(4):1167–91. doi:10.1016/j.ncl.2012.08.011.
14. Carskadon MA. Sleep in adolescents: the perfect storm. Pediatr Clin N
Am. 2011;58(3):637–47. doi:10.1016/j.pcl.2011.03.003.
15. Borbely AA. A two process model of sleep regulation. Hum Neurobiol.
1982;1(3):195–204.
16. Pigeon WR, Perlis ML. Sleep homeostasis in primary insomnia. Sleep
Med Rev. 2006;10(4):247–54.
10 Insomnia 171
17. Taylor DJ, Zimmerman MR, Gardner CE, Williams JM, Grieser EA,
Tatum JI, Bramoweth AD, Francetich JM, Ruggero C. A pilot randomized
controlled trial of the effects of cognitive behavioral therapy for insomnia
on sleep and daytime functioning in college students. Behav Ther.
2014;45(3):376–89.
18. de Bruin EJ, Oort FJ, Bögels SM, Meijer AM. Efficacy of internet and
group-administered cognitive behavioral therapy for insomnia in adoles-
cents: a pilot study. Behav Sleep Med. 2014;12(3):235–54.
19. Hendricks MC, Ward CM, Grodin LK, Slifer KJ. Multicomponent cogni-
tive-behavioural intervention to improve sleep in adolescents: a multiple
baseline design. Behav Cogn Psychother. 2014;42(3):368–73. doi:10.1017/
S1352465813000623).
Epilepsy and Sleep
in Adolescents 11
Sejal V. Jain and Sanjeev V. Kothare
Clinical Case 1
A 7-year-old boy presented with “weird episodes” in sleep noticed

by his parents. The episodes are described as flailing movements
of arm and leg, lasting 1–2 min, occurring multiple times through-
out the night and up to a few times per month. The patient typically
wakes up following episodes, is able to return easily to sleep, and
reports some recall for episodes upon morning awakening. The
mother has a history of sleepwalking.
Discussion
In the case described here, the patient could be having nocturnal

seizures or arousal parasomnia. The features suggestive of seizures
are occurrence any time throughout the night and multiple times in
S.V. Jain, M.D.

Division of Neurology and Pediatrics, Banner University Medical Center,
Tucson, AZ, USA
e-mail: svjain2012@gmail.com
New York, NY 10016, USA

174 S.V. Jain and S.V. Kothare
the night, and the patient being partially aware of the events.
However, these features do not rule out the possibility of parasom-
nia, especially in the presence of a positive family history.
Nocturnal Frontal Lobe Epilepsy (NFLE)
Nocturnal frontal lobe epilepsy is a distinct epilepsy syndrome

where most of the seizures occur in sleep. The onset occurs during
the first and second decade in life with peak in childhood. Seizures
are typically brief, stereotypic and occur multiple times in night.
Occasional daytime seizures may occur, especially during daytime
naps. Seizure semiology may include motor events with varying
complexity [1].
A genetically inherited form called autosomal dominant noc-
turnal frontal lobe epilepsy also exists, resulting from a mutation
in the genes coding for the alpha4 and beta2 subunits of the nico-
tinic acetylcholine receptor (CHRNA4 or CHRNB2) [2]. The
clinical manifestations can vary between individuals in the fam-
ily, but for the individual, the seizures are stereotypic. These can
include sudden awakenings with dystonic or dyskinetic move-
ments (42.1 %), complex behaviors (13.2 %), and sleep-related
violent behavior (5.3 %) [3]. The corresponding EEG findings
may include ictal epileptiform abnormalities predominantly over
frontal areas or rhythmic ictal slow wave activity over larger
anterior cortical areas (Fig. 11.1). However, EEG changes may
be difficult to identify due to movement artifact. The diagnosis
can be difficult, as EEG may not show interictal epileptiform dis-
charges and, during the events, movements may obliterate ictal
changes on EEG. Additionally, bizarre motor movements that are
typically seen with seizures can be obscure the EEG and increased
the probability of a misdiagnosis of a parasomnia or conversion
disorder. A polysomnography along with prolonged 16-channel
EEG may help to diagnose the syndrome. Multiple events
recorded on video and EEG helps to identify the stereotypic
semiology and EEG changes.
Treatment with oxcarbazepine or other antiepileptic drug with
efficacy against partial epilepsy is effective and in many cases,
control the seizures [1].
11 Epilepsy and Sleep in Adolescents 175
Fig. 11.1 Seizure onset from the frontal lobe
Parasomnia
According to the international classification of sleep disorders,

second edition (ICSD-3) [4], parasomnias are defined as undesir-
able physical events or experiences that occur during entry into
sleep, during sleep, or during arousals from sleep. They are classi-
fied as (1) disorders of arousals from non-rapid eye movement
(NREM) sleep; (2) parasomnias associated with rapid eye move-
ment (REM) sleep; and (3) other parasomnias. NREM parasom-
nias include sleepwalking, confusional awakenings, and night
terrors. REM sleep-related parasomnias include REM behavioral
disorder, sleep paralysis, nightmare disorder, and sleep-related
hallucinations. Sleepwalking, night terrors, confusional arousals,

and REM behavioral disorder may have complex motor activity
associated with the events that may make it difficult to differenti-
ate from NFLE. Treatment includes improving sleep quality,
reducing stress, and clonazepam or similar medications.
Coexistence and Differential Diagnosis
Derry et al. compared video EEG to identify semiological differen-

tiating features of the arousal parasomnias and NFLE [5]. The
results indicate that dystonic posturing and hyperkinetic automa-
tisms (such as kicking, rocking, or cycling movements) are specific
for NFLE, while complex fearful behaviors like sitting, standing,
or walking may be seen in both NFLE and parasomnias.
Additionally, presence of verbal interaction without motor features
is suggestive of NFLE and incomplete arousal suggests parasom-
nia [5]. A clinical decision tree has also been suggested where,
becoming fully conscious, sudden offset, dystonic posturing, and
not getting out of bed were more likely to be associated with sei-
zures [5]. Additionally, a frontal lobe epilepsy and parasomnias
(FLEP) score is also available to differentiate between the two.
However, these tools have some limitations [6]. An additional dif-
ferentiating point is the sleep stage from which the events occur:
most seizures occur out of stages 1 or 2 sleep, while true non-REM
parasomnias occurred out of stage 3 sleep. Video EEG recording
with comparing semiology of multiple events aided by EEG char-
acteristics may help the diagnosis [6]. While differentiating NFLE
from parasomnia is difficult, parasomnia and NFLE may coexist in
the same patient, making management even more challenging.
Provini et al. in a survey of 100 cases of NFLE showed that 39 % of
the patients reported a family history and in 34 %, a personal his-
tory positive for parasomnias [7]. Another study of 33 NFLE
patients and 200 relatives of the probands and controls and rela-
tives of controls showed that the prevalence of arousal disorders
(and nightmares) was more frequent among NFLE and their rela-
tives compared to the controls and their relatives, respectively [8].
The parasomnias of childhood were found to be replaced by NFLE
later in life in predisposed subjects [9]. These data suggest that
these disorders share some common pathways and various hypoth-

eses such as liberation, disassociation, and pathological arousals
may coexist [9].
Pitfalls
• The diagnosis of NFLE vs parasomnia is difficult.

• No acceptable diagnostic criteria exist.
Learning Points
• Both NFLE and parasomnia may coexist in a same patient.

• Video EEG and polysomnography may help diagnosis.
• Starting treatment may not help the diagnosis as up to a third of
the patients with NFLE may not respond to low dose
carbamazepine.
Clinical Case 2
An 18 years old boy presents to the clinic with recent breakthrough

seizures since 5 months. His seizures occur in the morning and
start with small jerks of the arm and progress to whole body jerk-
ing. These last for 1–2 min. He loses consciousness but denies
tongue bite, urinary or bowel incontinence. He is sleepy after he
gains consciousness. He was diagnosed with juvenile myoclonic
epilepsy (JME) 2 years ago and is treated with lamotrigine. Prior
to 5 months, his seizures were under control. He denies missing
any doses of medications. He denies any recent head trauma.
For the past 6 months, he has been a college freshman and lives
in the dorm. He reports difficulty falling asleep and has been stay-
ing awake until 2 am. He has classes at 8 am 3 days a week and has
trouble waking up for class. He has fallen asleep in class, typically
during the early morning hours. Once he falls asleep, he is able to
stay asleep. If he does not have classes, he sleeps in until 10–11 am.
Upon further questioning, he reports that he has “been partying till
late” and drinking alcohol.
Discussion
This case describes a teenager with JME who has recently transi-
tioned to college. He starts having breakthrough seizures, which
could be caused by sleep deprivation. In order to ensure adequate
treatment of both his sleep and epilepsy, it is important to deter-
mine the existence of behavioral factors (staying up late and “par-
tying”) and/or circadian factors (delayed sleep phase/irregular
sleep schedule) that could interfere with successful management.
Delayed Sleep-Wake Phase Disorder (DSWPD)
The international classification of sleep disorder (ICSD-3) [4]

defines DSWPD as: (1) a significant delay in the phase of the major
sleep episode in relation to the desired or required sleep time and
wake-up time for at least 3 months. When patients are allowed to
choose their ad libitum schedule, they will exhibit improved sleep
quality and duration for age and maintain a delayed phase of the
24-h sleep-wake pattern. Additionally, the delay in the timing of
the habitual sleep period is demonstrated on sleep log and, when
possible, on actigraphy, which should include both work/school
and free days. Moreover, these symptoms should not be better
explained by any other disorder, medication, or substance use.
Seven to sixteen percent of adolescents are reported to have
DSWPD. About 10 % of patients presenting with insomnia have
DSWPD. The disorder is characterized by a habitual delay in the
sleep-wake cycle by 2 h or more as compared to normally accept-
able social standards. This leads to difficulty in falling asleep at
socially acceptable time. Once sleep onset occurs, the sleep is typi-
cally of normal duration, which leads to difficulty waking up on
time for school, work, or other activities. The onset typically
occurs in adolescence but sometime onset is seen at an even earlier
age. The onset may follow environmental, psychological, or medi-
cal stresses. Untreated, it can persist in adulthood; however, bio-
logical advance in sleep phase with increasing age may resolve the
condition. Untreated, the patient can turn to stimulants, which may
cause substance abuse issues. The patients tend to have evening-
type chronotype and are prone to mood disorders.
There are multiple factors that predispose or precipitate this

disorder. Family history is present in 40 % of the patients.
Additionally, polymorphisms in Per3, arylalkylamine
N-acetyltransferase, human leukocyte antigen, and Clock genes
such as BMAL have been suggested to be associated with
DSWPD. Environmental factors such as decreased exposure to
light during morning and midday may also influence it. Social,
behavioral, and occupational factors requiring activities in evening
hours may also contribute to DSWPD. Diagnosis is based on the
history and sleep logs. Actigraphy spanning over 14 days, includ-
ing weekend or off days, will help to identify delay on free nights.
Dim light melatonin onset (DLMO) and core body temperature
rhythm are in synch with the delayed sleep onset. Behaviorally
induced delay has to be differentiated from DSWPD. Detail his-
tory can help differentiate DSWPD from behavioral symptoms.
In DSWPD, sleep quality and quantity is normal once the patient
is sleeping at the desired time. Additionally, core body tempera-
ture and DLMO are not in synch with the late sleep onset in behav-
ioral symptoms.
Treatment involves phototherapy in the morning, reduced
bright light exposure in evenings, and melatonin to advance the
sleep phase.
Juvenile Myoclonic Epilepsy (JME)
JME is a relatively common and easily recognizable epilepsy syn-

drome, which has been described for over 200 years. In 1989, The
International League Against Epilepsy (ILAE) reported that JME
appears around puberty and is characterized by seizures with bilat-
eral, single or repetitive, arrhythmic, irregular myoclonic jerks,
predominantly in the arms. Jerks may cause some patients to fall
suddenly. No disturbance of consciousness is noticeable. The dis-
order may be inherited, and sex distribution is equal. Often, there
are generalized tonic–clonic seizures and, less often, infrequent
absences. The seizures usually occur shortly after awakening and
are often precipitated by sleep deprivation. Interictal and ictal
EEGs have rapid, generalized, often irregular spike–waves and
polyspike–waves; there is no close phase correlation between EEG
spikes and jerks. Frequently, the patients are photosensitive.

Response to appropriate drugs is good [10]. The prevalence of
JME has been estimated to be 0.1 to 0.2 per 100,000 with a peak
age of onset of 12–18 years. Three seizure types occur in patients
with JME: (1) early morning myoclonic jerks, (2) generalized
tonic–clonic seizures, and (3) absence seizures with the myoclonic
jerks being the most common and absence being the least. All
three seizure types are seen in a third of patients. These patients
are typically brought to medical attention after a generalized sei-
zure, which follows the onset of myoclonic jerks by 1.3–3.3 years.
Circadian distribution of the seizures is a major feature of the syn-
drome with most myoclonic jerks and generalized seizures occur-
ring in the early morning hours and during awakenings from sleep
[11]. In a study, the occurrence of generalized seizures was noted
between 6 am–12 pm [12]. In about 15 % of patients, the seizures
are provoked by flickering light. This phenomenon is called a pho-
toparoxysmal response, which can also be seen on EEG when
flashing light induces an electrographic seizure on the EEG [13].
Some of the most common precipitating factors are sleep depriva-
tion and alcohol consumption [11]. The diagnosis is assisted by the
presence of polyspike and wave discharges on EEG. Broad spec-
trum antiepileptic drugs like valproic acid, lamotrigine, and leveti-
racetam are effective in controlling the seizures [14].
Lifestyle modification is a mainstay in the management of these
patients. Adequate quantity of sleep and regular sleep-wake cycle
are essential in preventing breakthrough seizures. Lamotrigine
may induce insomnia, so it should be given earlier in the evening.
Alcohol, caffeine, and energy drinks should also be limited [14].
In addition to delayed sleep phase, other sleep disorders may
also occur in patients with epilepsy. Obstructive sleep apnea occurs
in epilepsy, especially in refractory epilepsy, at a higher prevalence
than in the general population [15]. Moreover, epilepsy patients
who use vagal nerve stimulator also have a higher prevalence of
OSA, as well as central apneic events. These seem to be higher
with higher frequency of stimulation of the vagus nerve. In addi-
tion to standard treatment of OSA, reduction in stimulation dura-
tion and frequency may help [16, 17].
Pitfalls
• Poor behavioral habits and occupational demands may appear

to be falsely diagnosed as delayed sleep phase syndrome. Sleep
disorders such as obstructive sleep apnea, or insomnia may also
be seen in patients with JME.
Learning Points
• JME onset is in adolescence, similar to DSWPD.

• Sleep deprivation and alcohol consumption can worsen the sei-
zure control in JME.
• DSWPD and other sleep disorders should be identified and
treated to facilitate seizure control in these patients.
• Alerting AEDs such as lamotrigine should be given earlier in
the evening, so as to avoid insomnia.
• Lifestyle modification is an important part of the management
for JME.
Clinical Case 3
A 20-year-old female with known JME presents to the clinic with

symptoms of excessive sleepiness, fragmented sleep at night, and
symptoms suggestive of depression. She also complains of having
vivid dreams when she falls asleep and inability to move body
parts when she arouses suddenly. She also complains of brief
slurred speech when she is laughing or excited. She was diagnosed
with JME at 16 years of age and she is taking levetiracetam. She
takes her medications regularly and has been seizure free for
3 years. She denies using stimulants/coffee in the evening. She
denies the use of TV, computer, etc. before bedtime. She wakes up
a few times in the night and is unable to return back to sleep. She
is tired through the day and takes 1–2 naps lasting 30 min. She
feels refreshed after the nap. She is also being evaluated by psy-
chiatry for a mood disorder.
Discussion
The case describes a young woman with the diagnosis of JME and
sleepiness. The sleepiness in patients with epilepsy can be multi-
factorial, caused by changes in antiepileptic drugs, poor quality
sleep that is associated with epilepsy, and poor behavior/psychiat-
ric disorders that are associated with epilepsy. In this case how-
ever, additional symptoms are very suggestive of narcolepsy. It is
important to get a proper history, as sleep paralysis and cataplexy
may be missed as symptoms of seizures.
JME
As discussed above, JME is an epilepsy syndrome with onset in

adolescence and young adulthood. Genetic mutations have been
identified in families and individuals. In 49 % of the families with
JME, an autosomal dominant mode of transmission is seen.
Various genetic loci have been identified, including genes located
on chromosome 6, such as EJM, EJM3, and JME. Specific genes
have also been identified that make an individual susceptible for
photosensitivity and a photoparoxysmal response on EEG [18].
Narcolepsy
Narcolepsy is also a rare disorder with prevalence of the symptoms

beginning in the first or second decade of life. It includes a tetrad
of excessive sleepiness, cataplexy, sleep paralysis, and hypnagogic
hallucinations. Additionally, fragmented sleep is also present.
Diagnosis is confirmed by a polysomnography with a multiple
sleep latency test (MSLT), which may show fragmented nocturnal
sleep and mean sleep latency <8 min during the day. Additionally,
low CSF-hypocretin levels may also be seen. The vast majority of
patients with sporadic onset and almost all patients with acute
onset narcolepsy with cataplexy following an H1N1 infection are
positive for human leukocyte antigen (HLA) allele DQB1*0602.
Treatment options include stimulants, sodium oxybate, modafinil,
and selective serotonin reuptake inhibitors [19].
The Interaction
In a recent study, three women were identified to have both JME

and narcolepsy out of 50,000 patients searched. This suggested
that the prevalence of coexistence of this disorder is much higher
than expected by chance 91/2,000,000 [20]. Another case series
also described coexistence of narcolepsy type 1 with idiopathic
generalized epilepsy including JME [21]. This discovery led to the
hypotheses that certain genetic factors may be contributing to the
co-occurrence of the disease. The HLA-DQB1 gene is located on
the short arm of the chromosome 6 at position 6p21.3, while the
JME gene EJM has been mapped to chromosome 6p21.2-p11 and
on 6p21.3 on a 10.1 cM region flanked by HLA-DQA1 and the
short tandem repeat polymorphism marker D6S1019. Hence, the
genes responsible for both the diseases coexist on same region on
chromosome 6. This suggests that the diseases may coexist [20].
Therefore, providers should be vigilant in screening of these disor-
ders in patients with a concomitant diagnosis. Stimulant medica-
tions and sodium oxybate have been shown to be safe to use in
epilepsy patients [20, 21].
Pitfalls
• The diagnosis of narcolepsy in JME may be difficult as some of

the antiseizure drugs may cause sleepiness and providers may
attribute sleepiness to the medications.
• Sleep fragmentation and poor sleep quality are also common in
patients with epilepsy, which may also present as sleepiness [22].
Learning Points
• JME and narcolepsy may coexist due to common genetic loci

on chromosome 6.
• The identification and diagnosis of coexisting disorder may be
difficult.
• Stimulants are safe to use in patients with epilepsy.
• Psychiatric disorders may also coexist.

References
1. Nobili L, et al. Nocturnal frontal lobe epilepsy. Curr Neurol Neurosci Rep.
2014;14(2):424.
2. Kothare SV, Kaleyias J. Sleep and epilepsy in children and adolescents.
Sleep Med. 2010;11(7):674–85.
3. Oldani A, et al. Autosomal dominant nocturnal frontal lobe epilepsy. A
video-polysomnographic and genetic appraisal of 40 patients and delinea-
tion of the epileptic syndrome. Brain. 1998;121(Pt 2):205–23.
4. Medicine AAOS, editor. International classification of sleep disorders. 3rd
ed. Darien, IL: American Academy of Sleep Medicine; 2014.
5. Derry CP, et al. NREM arousal parasomnias and their distinction from
nocturnal frontal lobe epilepsy: a video EEG analysis. Sleep. 2009;32(12):
1637–44.
6. Bisulli F, et al. Parasomnias and nocturnal frontal lobe epilepsy (NFLE):
lights and shadows—controversial points in the differential diagnosis.
Sleep Med. 2011;12 Suppl 2:S27–32.
7. Provini F, et al. Nocturnal frontal lobe epilepsy. A clinical and polygraphic
overview of 100 consecutive cases. Brain. 1999;122(Pt 6):1017–31.
8. Bisulli F, et al. Increased frequency of arousal parasomnias in families
with nocturnal frontal lobe epilepsy: a common mechanism? Epilepsia.
2010;51(9):1852–60.
9. Halasz P, Kelemen A, Szucs A. Physiopathogenetic interrelationship
between nocturnal frontal lobe epilepsy and NREM arousal parasomnias.
Epilepsy Res Treat. 2012;2012:312693.
10. Genton P, Gelisse P. The history of juvenile myoclonic epilepsy. Epilepsy
Behav. 2013;28 Suppl 1:S2–7.
11. Genton P, et al. Clinical aspects of juvenile myoclonic epilepsy. Epilepsy
Behav. 2013;28 Suppl 1:S8–14.
12. Zarowski M, et al. Circadian distribution and sleep/wake patterns of
generalized seizures in children. Epilepsia. 2011;52(6):1076–83.
13. Serafini A, et al. Neurophysiology of juvenile myoclonic epilepsy.
Epilepsy Behav. 2013;28 Suppl 1:S30–9.
14. Crespel A, et al. Management of juvenile myoclonic epilepsy. Epilepsy
Behav. 2013;28 Suppl 1:S81–6.
15. Jain SV, Kothare SV. Sleep and epilepsy. Semin Pediatr Neurol.
2015;22(2):86–92.
16. Parhizgar F, Nugent K, Raj R. Obstructive sleep apnea and respiratory
complications associated with vagus nerve stimulators. J Clin Sleep Med.
2011;7(4):401–7.
17. Khurana DS, et al. Vagus nerve stimulation in children with refractory
epilepsy: unusual complications and relationship to sleep-disordered
breathing. Childs Nerv Syst. 2007;23(11):1309–12.
18. Delgado-Escueta AV, et al. The quest for juvenile myoclonic epilepsy
genes. Epilepsy Behav. 2013;28 Suppl 1:S52–7.
19. Dye TJ, Jain SV, Kothare SV. Central hypersomnia. Semin Pediatr Neurol.
2015;22(2):93–104.
20. Joshi PA, Poduri A, Kothare SV. Juvenile myoclonic epilepsy and narco-
lepsy: a series of three cases. Epilepsy Behav. 2015;51:163–5.
21. Baiardi S, et al. Narcolepsy Type 1 and idiopathic generalized epilepsy:
diagnostic and therapeutic challenges in dual cases. J Clin Sleep Med.
2015;11(11):1257–62.
22. Ramachandraiah CT, et al. Interrelationship of sleep and juvenile myo-
clonic epilepsy (JME): a sleep questionnaire-, EEG-, and polysomnogra-
phy (PSG)-based prospective case–control study. Epilepsy Behav.
2012;25(3):391–6.
Traumatic Brain Injury
12
Kanwaljit Singh and Sanjeev V. Kothare
Clinical Case 1: Posttraumatic Narcolepsy
An 18-year-old football player sustained a concussion during a

game session when he collided with another player. He reportedly
lost consciousness for a brief period of time following the accident
and subsequently complained of headaches, dizziness, confusion,
and nausea for a few weeks following the incident. His brain imag-
ing studies were normal. Subsequently, he manifested with mild
cataplexy; excessive daytime sleepiness; vivid dream mentations;
and fragmented sleep consistent with narcolepsy type 1 [1]. There
was no history of seizure or sleep disorder prior to the accident.
He reported no family history of sleep disorders. The Epworth
Sleepiness Scale revealed a score of 13 [2]. Sleep studies
(Polysomnography and Multiple Sleep Latency Test) were per-
formed to confirm the diagnosis of narcolepsy. Mean sleep latency
K. Singh, M.D.
Department of Pediatrics (Neurology), University of Massachusetts
Medical School, Worcester, MA, USA
e-mail: kanwaljit.singh@umassmed.edu
Department of Neurology, NYU Langone Medical Center and NYU
School of Medicine, 223 East 34th Street, New York, NY 10016, USA

188 K. Singh and S.V. Kothare
(mean of the time to sleep onset during the 5 naps), and rapid eye
movement sleep latency (time from sleep onset to rapid eye move-
ment sleep onset), during the MSLT were shortened at 2, 3, and
10 min, respectively), while the sleep study showed mild periodic
limb movements of sleep (8/h) fragmented sleep characterized by
an arousal index of 30/h (normal < 10/h) and sleep efficiency at
58 % (normal > 85 and an early sleep onset REM latency of 8 min.
Twenty-four-hour electroencephalography and repeat magnetic
resonance imaging of the brain were normal. The serum chemistries
were normal as well.
Initially he was put on a course of daytime caffeine combined
with a sleep hygiene program, which failed to make any significant
impact on his symptoms. He was then started on a course of
modafinil 100 mg twice a day; one dose in the morning upon
awakening and a second dose at midday. He was also given a trial
with oral amantadine 100 mg three times a day for improving his
alertness. Within a month of starting this regimen, his cataplexy
and excessive daytime sleepiness started to improve without any
further dose titration. He reported no significant adverse effects
from modafinil. Three months later, his amantadine was discontin-
ued. Six months after the initiation of modafinil therapy, the patient
is completely asymptomatic. The plan would be to stop his
modafinil to assess for a spontaneous remission of his symptoms.
Learning Points
• Sleep problems often develop after an episode of TBI, even in

cases of mild TBI. Treating physician should be aware of such
an outcome and seek to actively manage them.
Pitfalls
• Missing or failing to anticipate development of sleep disorders

in TBI may lead to worsening of the symptoms, school absences
and may add to the comorbidity.
12 Traumatic Brain Injury 189
Clinical Case 2: Poor Sleep Hygiene

Following Traumatic Brain Injury
A 13-year-old boy reported to our clinic with complaints of sleep

onset and maintenance insomnia coupled with excessive daytime
sleepiness leading him to miss out on school. He is an avid baseball
player at school and 2 months ago he suffered from a moderate
traumatic brain injury when he was hit on his head with the base-
ball bat accidentally swung by another player. He briefly lost con-
sciousness following this incident and was admitted to the ER
overnight for observation and evaluation. Brain imaging was nor-
mal. He has had no past or family history of any sleep problems.
As per his social history he is a prolific video gamer and on week-
ends and during holidays he would spend several hours playing
video games late into the night. He was advised a “week of brain
rest” from school after the injury, during which time he watched
TV on a continuous basis into the late hours of the night, while
taking multiple daytime naps, and spending the rest of the time in
bed in front of the TV.
When he resumed school, he had difficulty with concentration
in the daytime and difficulty falling asleep and maintaining sleep
at night. He continued with daytime naps and lost multiple school
days. This caused his parents to bring him to our sleep center for
evaluation with a risk of truancy as threatened by the school.
Based on his history, his parents were advised to maintain detailed
sleep logs for at least 2 weeks documenting his exact sleep and
wake hours. These logs confirmed poor sleep efficiency, sleep
onset and sleep maintenance insomnia, with daytime naps. He was
started on daytime armodafinil plus a vigorous exercise regimen.
He was asked to take bright light via a light box in the morning and
was started on 3 mg melatonin at night at a chrono-hypnotic dose.
He was asked to not nap in the daytime and avoid TV and other
sources of social media after 8 pm. Within 4 weeks of this regi-
men, his sleep problems gradually started to subside and within
2 months, his sleep schedule was back to normal.
Learning Points
• Poor sleep hygiene can complicate recovery after traumatic

brain injury, worsening sleep problems and causing school
absenteeism.
• Forced brain rest after TBI as being advocated by schools and
Centers for Disease Control and Prevention can be helpful in
encouraging recovery post-injury, but may worsen sleep prob-
lems due to excess TV viewing and being on social media at
night.
• Educating families about this risk and maintaining strict sleep–
wake schedules may prevent this complication.
Pitfalls
• The “brain rest” period also has the potential to actually worsen
sleep problems if handled incorrectly. For example, the person
who is on brain rest spending their evenings watching TV can
quickly exacerbate their sleep problems. It is very important to
spend the “rest period” by actually giving complete cognitive
rest to the brain, especially in the evenings.
Clinical Case 3: Posttraumatic Hypersomnia

Unmasking Autoimmune Encephalitis
A high school student in his late teens and an accomplished ice

hockey player presented with complains of inattention, memory
problems, and sleep issues after sustaining a mild TBI. He had an
unremarkable past medical history, although he reported occa-
sional episodes of binge drinking on the weekend and recreational
drug use. There was no past history of brain injury or other neuro-
logical problems or a past history of sleep disorder. He suffered an
episode of mild TBI when he slipped on ice and hit his head on the
railing. Except for a brief period of disorientation, his immediate
post-injury recovery was uneventful. The CT scan done at the hos-
pital within hours of the incident was normal as well. After an
overnight observation, he was discharged from the hospital.
One-month post-injury he presented at the outpatient clinic

with complaints of problem with impaired attention, processing,
and memory. He had fragmented sleep, which was disrupted with
frequent brief awakenings. He reported significant difficulties fall-
ing and staying asleep and had daytime sleepiness and fatigue,
which affected his ability to participate in school activities at least
several times per week. He reported that he went to bed between
12 am and 1 am and it took him around 1 h to fall asleep, he got up
2–3 times per night and then had difficulty getting back to sleep.
He frequently woke up late, around 9.30–10 am and was report-
edly getting frequently fatigued during the daytime. In addition, he
had started noticing that he got anxious and irritable very easily.
He also reported a feeling of weakness on right side along with a
loss of balance, ataxia and involuntary movements of hands, cog-
nitive impairment, memory disturbances and delusions, as well as
visual hallucinations. Initially his symptoms were suspected of
being typical sleep impairment due to the TBI, and a typical regi-
men of stimulant medications (methylphenidate) in combination
with strict sleep hygiene was instituted.
However, 2 months of this treatment failed to elicit any
improvement in his sleep difficulties as well as his coordination
and psychiatric problems. This led to suspicion of an autoimmune
component to his sleep, memory, coordination, and psychiatric
problems. A subsequent MRI was done which was normal. Occult
tumor workup for a neuroblastoma and teratoma was negative.
EEG was abnormal, showing diffuse slowing of the background in
the delta-theta range with excessive spindling seen during sleep.
Cerebrospinal fluid (CSF) analysis and blood showed presence of
N-methyl-d-aspartate (NMDA) receptor antibodies in moderately
high titers. Accordingly, a trial with methylprednisolone (1 g daily
for 5 days) followed by immune globulin (0.4 g/kg daily for
5 days) was instituted, which leads to a rapid improvement in his
symptoms. He remains now in remission for over 6 months.
Learning Points
• If a TBI patient with sleep problems does not respond to the

typical regimen of stimulants and sleep hygiene, and instead
develops psychiatric manifestations, cognitive impairment, and

coordination issues, an autoimmune component complicating
his sleep problems should be suspected. In such cases, the TBI
may have unmasked a pre-existing, asymptomatic autoimmune
problem.
Pitfalls
• Missing the diagnosis of concomitant autoimmune disease may

result in a lost opportunity to reverse this condition and improve
overall quality of life.
Discussion
These clinical cases demonstrate the spectrum of sleep distur-

bances that can occur in cases of traumatic brain injury. The
regions of brain regulating arousal, alertness, attention, and sleep
are very vulnerable to TBI, hence the sleep and wakefulness cycles
often become disturbed with brain injury, irrespective of the sever-
ity [3, 4]. Recent research has indicated that the prevalence of
sleep disorders in TBI may be as high as 30–70 % [5–7]. Sleep
disorders can occur with TBI without regard to the severity of
injury, and even mild cases of TBI have been associated with prob-
lems such as sleep fragmentation and reduced sleep quality [8, 9].
In a study done in the outpatient setting, at least 30–50 % of
patients with minor TBI complained of insomnia, the majority of
whom had early awakenings, and some had sleep onset insomnia
[10]. Another study showed that in patients with mild TBI referred
for sleep problems, 36 % had a circadian rhythm disorder [11].
A broad spectrum of sleep disorders is associated with TBI, and
includes diagnoses such as hypersomnia, insomnia, sleep-related
breathing disorders (obstructive sleep apnea), movement disorders
such as periodic limb movement of sleep (PLMS), and narcolepsy
as well as self-reported problems such as poor sleep efficiency,
snoring, excessive daytime sleepiness, and poor sleep quality [12].
Sleep apnea, posttraumatic hypersomnia, narcolepsy, and periodic
limb movements of sleep are amongst the most common sleep dis-
orders diagnosed after TBI [13]. Excessive daytime sleepiness
(EDS) in conjunction with nighttime difficulty initiating or main-
taining sleep is also common after TBI, especially in patients
recently discharged from hospital after TBI [14] with various stud-
ies indicating a prevalence ranging from 25–52 % [15–18].
Symptoms of cognitive impairment have also been associated with
TBI and are correlated with increasing severity of injury [19].
Interestingly, patients with TBI and sleep disordered breathing
have a higher likelihood of impaired cognitive impairment, such as
problems with memory and sustained attention [16].
The prevalence of periodic limb movement of sleep (PLMS) in
institutionalized TBI patients was reported to be as high as 25.4 %
[17] while in another multicentered study, 17 % of both institution-
alized and ambulatory TBI patients had PLMS [15]. Another study
found the prevalence of parasomnias (most often REM behavior
disorder) in 25 % of patients with TBI [18].
Mechanisms of Sleep Disturbance After TBI
The mechanism behind sleep disturbances in TBI is likely multi-

factorial. Many brain regions, pathways, and neurotransmitter sys-
tems associated with sleep regulation, including the suprachiasmatic
nucleus, hypothalamus, midbrain, and ascending reticular activat-
ing system, are vulnerable to TBI [6]. Specifically, impaired hypo-
cretin (orexin) signaling and injury to sleep–wake modulating
systems in the brain stem and the mesencephalon play a significant
contributing role to impaired sleep in TBI [20–22]. Recent studies
have implicated damage to the histaminergic tuberomammillary
neurons as a contributing factor to impaired sleep–wake cycle in
TBI [23]. A study on severe TBI found a significant loss of the
wakefulness promoting histaminergic neurons in the tuberomam-
millary neurons, and of the melanin concentrating hormone and
orexin-A neurons [23].
One study has shown a possible disruption of circadian synthe-
sis of melatonin after TBI. A circadian pacemaker in the hypotha-
lamic suprachiasmatic nuclei regulates circadian rhythms in
humans. This system includes the production of melatonin from

the pineal gland. Lower levels of evening melatonin production
have been shown in individuals with TBI, which in turn was asso-
ciated with alteration of REM sleep [24]. In patients with exces-
sive daytime sleepiness who have had an episode of mild to
moderate TBI, reduced cortical excitability as measured by tran-
scranial magnetic stimulation has been demonstrated as late as
3 months after the injury. The authors speculate that this finding
may be due to an impaired excitatory hypocretin/orexin neu-
rotransmitter system, which has been associated with excessive
daytime sleepiness and hypersomnia [25].
Some investigators have hypothesized that sleep problems in
brain injury occur due to injury to the brain regions of ascending
reticular activating system, limbic system, and the basal ganglia,
thus affecting the striatal-thalamic-frontal cortical system [26].
This hypothesis was supported by subsequent observations in
patients with TBI showing increased brain activity in several
regions such as middle frontal, superior parietal, basal ganglia, and
anterior cingulate regions while performing a cognitive task [27].
There are several secondary factors implicated in sleep disor-
ders in TBI. Some of them include pain, depression, and anxiety
[5, 28]. In a study evaluating concussed in athletes, patients with
sleep complains were 3 times more likely to have concomitant
headaches in the first 6 weeks following a mild TBI. Interestingly,
impaired sleep was only correlated with pain from injury during
the first few weeks following the injury. Later on, symptoms such
as frequent nighttime awakenings continued independent from
pain [29] Some studies have shown depression exacerbating some
symptoms of sleep problems after TBI [24]. Recent research has
shown that patients who complained of moderate/severe head-
aches, dizziness, and psychiatric manifestations after a mild case
of traumatic brain injury were more likely to develop moderate/
severe sleep problems later on [30]. Another secondary factor
impacting sleep in TBI is fatigue. Fatigue may result in increased
frequency of daytime napping, which in turn may have an impact
on nighttime sleep quality.
The relationship of unmasking autoimmune encephalitis (AE)
after TBI as discussed in case 3 is conjectural, though we have
seen at least 6–7 cases of AE following TBI involving NMDA,

voltage gated potassium channelopathy (VGKC), and anti-
glutamic acid decarboxylase antibody (GAD) syndrome (unpub-
lished data). The comorbid burden of sleep disorders following AE
is well known and we recently published a case of recurrent insom-
nia secondary to anti-GAD antibody syndrome [31].
Assessment of Sleep Disorders in TBI
A detailed medical, psychiatric, sleep, and family history should

be obtained as the first step towards evaluating sleep disorders in
TBI [32]. The sleep history in particular should focus on sleep tim-
ings, such as time to go to bed, wake-up time, daytime sleepiness,
and any problems with initiating and maintaining sleep during the
night. A psychiatric consultation may be considered if suspicion of
a coexisting disorder such as anxiety or depression that may also
affect sleep is present. Family history should be obtained for
insomnia or other sleep problems. Another important aspect of
assessing sleep problems in TBI is recognizing any pre-existing
sleep problems (prior to TBI), and those patients with pre-existing
sleep issues will likely have more severe sleep problems post-
TBI. Therefore, questionnaires focused on pre-TBI and post-TBI
sleep complaints will help identify particularly impaired patients.
Once a sleep problem has been identified, actigraphy in con-
junction with detailed sleep logs, and in some cases sleep studies
may be useful in identifying the severity of the problem. Sleep
logs and actigraphy are helpful in identifying patterns with sleep
hygiene, nighttime sleep issues (irregular, excessive, or insuffi-
cient sleep), insomnia (whether it is sleep onset or sleep mainte-
nance), excessive daytime sleepiness, or circadian rhythm
disorders, as well as help educate patients and to evaluate the treat-
ment effectiveness.
The literature on usefulness of sleep studies in TBI has shown
mixed results. Some studies have found increased sleep fragmenta-
tion and increased sleep onset latency [5, 8]. Others have shown
reduced sleep efficiency [33]. However, a few studies could not find
any differences in sleep onset latency [34]. One study also found
reduced rapid eye movement (REM) sleep [34], yet another found
increased REM sleep in the second half of the night [35], one found
decreased REM onset latency [33], and another found increased N3
sleep [36] in patients with TBI. Another study found no differences
whatsoever in TBI patients as compared to healthy controls [33].
Therefore, sleep studies, such as polysomnography, and other
modalities such as maintenance of wakefulness tests and multiple
sleep latency tests (MSLT) may have limited utility in TBI. As a first
step, suspected insomnia cases can be evaluated using standard
insomnia questionnaires and sleep logs. If expected progress is not
achieved, objective tests should be considered to determine other dis-
orders, such as sleep-related breathing (obstructive sleep apnea, sleep
disruptive snoring), movement disorders such as PLMS, atypical
EEG arousal bursts and conditions such as narcolepsy, hypersomnia,
and parasomnias complicating the sleep problems in this population.
Management of Sleep Disorders With TBI
An optimal combination of sleep education combined with good

sleep hygiene, behavioral interventions, and pharmacologic inter-
vention are essential for successful management of sleep problems
in TBI (Table 12.1). Once a diagnosis is identified, appropriate
interventions include medications, behavioral measures, and/or
psychological counseling which should be instituted to manage
the sleep problems. Treatment should be tailored to the specific
disorder, as well as to any comorbid post-TBI symptoms, which
might require a multidisciplinary approach [37–39]. Patient edu-
cation is an important aspect of successful management of post-
TBI sleep complains, and will help improve patient compliance as
well as prevent any recurrences [40].
Medications such as stimulants (methylphenidate, dextroam-
phetamine, modafinil, armodafinil) are helpful in hypersomnia
[38], circadian rhythm disorder [39], and narcolepsy [32] by pro-
moting wakefulness during the day. Supplementation with melato-
nin is also helpful in patients with insomnia [37], and circadian
rhythm disorder [39]. Amantadine is helpful in improving alert-
ness in some TBI patients. It has been shown that TBI patients
treated with amantadine reported improvements in motivation,
attention, concentration, alertness, and executive functioning;
Table 12.1 Treatment considerations for sleep disorders in patients follow-

ing traumatic brain injury. Adapted from Singh et al. [32]
Sleep disorder Treatment optionsa
Insomnia [37]
Primary Sleep hygiene, cognitive behavioral therapy
(CBT), +/− melatonin, hypnotics, acupuncture
Secondary
Due to PTSD
SSRIs, psychology counsel, pain management
Due to pain counsel, CBT, sleep hygiene, +/− melatonin
Due to depression
Hypersomnia Stimulant medications (i.e., methylphenidate,
dextroamphetamine, modafinil, armodafinil)
[38]
Obstructive sleep apnea CPAP, surgical interventions, mandibular
devices, weight loss
Periodic limb movements Iron supplementation, dopamine agonists,
of sleep/restless leg gabapentin
syndrome
Circadian rhythm disorder Melatonin supplementation, +/− stimulant
[39] medication in daytimeb, +/− hypnotic
medication in eveningb, bright light therapy in
Delayed sleep phase AM/reduced light exposure in PM, prescribed
sleep/wake scheduling, sleep hygiene
education
Advanced sleep phase Advance chronotherapy (bright light therapy
in PM/reduced light exposure in AM),
+/− melatoninb, sleep hygiene education,
prescribed sleep/wake scheduling
Narcolepsy Stimulant medications (i.e., methylphenidate,
dextroamphetamine, modafinil, armodafinil),
sodium oxybate
a
All patients should be educated on future TBI prevention and consequence of
recurrent TBI
b
There is insufficient evidence to support the efficacy or safety of these medi-
cations in these disorders
reduced apathy, agitation, distractibility, fatigue, aggression, and

anxiety have also been reported [41]. Iron supplementation, dopa-
mine agonists, or gabapentin can be helpful in cases with periodic
limb movement of sleep and/or restless leg syndrome [32].
Forced brain rest/cognitive rest in which the individual with TBI
takes plenty of rest is very important and promotes brain healing,
and in turn prevents deterioration of any sleep problems. This
includes avoiding activities that are physically demanding and
those that require a lot of mental concentration, avoiding contact
sports, avoiding alcoholic beverages, and instituting good sleep
hygiene [42, 43]. Good sleep hygiene involves a combination of set
bedtime routines and also habits during the daytime and evening
which ensure an optimal sleep environment. It is important to limit
daytime, especially evening, naps and to avoid caffeine intake.
Limiting evening time visual stimulation and exposure to bright
lights (by way of avoiding television screens) will promote good
nighttime sleep habits. Limiting evening exposure to television and
bright lights is especially helpful because there have been studies
demonstrating a decrease in urinary excretion of melatonin metab-
olites after daily evening exposure to television for 1 week [44] and
suppression of melatonin secretion and a reduction of presleep
melatonin levels after exposure to bright lights [45]. Maintaining a
consistent night-to-night bedtime routine with as little variability as
possible is an important part of good sleep hygiene. Once estab-
lished, most patients will respond well to these bedtime routines.
In conclusion, sleep problems are an under-recognized problem
in patients with TBI. Better screening for these disorders and
appropriate management will lead to improved quality of life in
this population.

References
sleep disorders, Diagnostic and coding manual. 3rd ed. Chicago, IL:
American Academy of Sleep Medicine; 2014.
2. Johns MW. A new method for measuring daytime sleepiness: the Epworth
sleepiness scale. Sleep. 1991;14:540–5.
3. Mathias JL, Alvaro PK. Prevalence of sleep disturbances, disorders, and
problems following traumatic brain injury: a meta-analysis. Sleep Med.
2012;13:898–905.
4. Guilleminault C, Yuen KM, Gulevich MG, Karadeniz D, Leger D, Philip
P. Hypersomnia after head-neck trauma: a medicolegal dilemma.
Neurology. 2000;54:653–9.
5. Ouellet MC, Beaulieu-Bonneau S, Morin CM. Insomnia in patients with
traumatic brain injury: frequency, characteristics, and risk factors. J Head
Trauma Rehabil. 2006;21:199–212.
6. Baumann CR, Werth E, Stocker R, Ludwig S, Bassetti CL. Sleep-wake
disturbances 6 months after traumatic brain injury: a prospective study.
Brain. 2007;130:1873–83.
7. Borgaro SR, Baker J, Wethe JV, Prigatano GP, Kwasnica C. Subjective
reports of fatigue during early recovery from traumatic brain injury.
J Head Trauma Rehabil. 2005;20:416–25.
8. Kaufman Y, Tzischinsky O, Epstein R, Etzioni A, Lavie P, Pillar G. Long-
term sleep disturbances in adolescents after minor head injury. Pediatr
Neurol. 2001;24:129–34.
9. Parsons LC, Ver Beek D. Sleep-awake patterns following cerebral concus-
sion. Nurs Res. 1982;31:260–4.
10. Fichtenberg NL, Zafonte RD, Putnam S, Mann NR, Millard AE. Insomnia
in a post-acute brain injury sample. Brain Inj. 2002;16:197–206.
11. Ayalon L, Borodkin K, Dishon L, Kanety H, Dagan Y. Circadian rhythm
sleep disorders following mild traumatic brain injury. Neurology.
2007;68:1136–40.
12. Viola-Saltzman M, Watson NF. Traumatic brain injury and sleep disor-
ders. Neurol Clin. 2012;30:1299–312.
13. Castriotta RJ, Murthy JN. Sleep disorders in patients with traumatic brain
injury: a review. CNS Drugs. 2011;25:175–85.
14. Cohen M, Oksenberg A, Snir D, Stern MJ, Groswasser Z. Temporally
related changes of sleep complaints in traumatic brain injured patients.
J Neurol Neurosurg Psychiatry. 1992;55:313–5.
15. Castriotta RJ, Wilde MC, Lai JM, Atanasov S, Masel BE, Kuna
ST. Prevalence and consequences of sleep disorders in traumatic brain
injury. J Clin Sleep Med. 2007;3:349–56.
16. Wilde MC, Castriotta RJ, Lai JM, Atanasov S, Masel BE, Kuna
ST. Cognitive impairment in patients with traumatic brain injury and
obstructive sleep apnea. Arch Phys Med Rehabil. 2007;88:1284–8.
17. Masel BE, Scheibel RS, Kimbark T, Kuna ST. Excessive daytime sleepi-
ness in adults with brain injuries. Arch Phys Med Rehabil.
2001;82:1526–32.
18. Verma A, Anand V, Verma NP. Sleep disorders in chronic traumatic brain
injury. J Clin Sleep Med. 2007;3:357–62.
19. Dikmen S, Machamer J, Temkin N, McLean A. Neuropsychological

recovery in patients with moderate to severe head injury: 2 year follow-up.
J Clin Exp Neuropsychol. 1990;12:507–19.
20. Baumann CR, Stocker R, Imhof HG, et al. Hypocretin-1 (orexin A) defi-
ciency in acute traumatic brain injury. Neurology. 2005;65:147–9.
21. Baumann CR, Bassetti CL, Valko PO, et al. Loss of hypocretin (orexin)
neurons with traumatic brain injury. Ann Neurol. 2009;66:555–9.
22. Crompton MR. Hypothalamic lesions following closed head injury. Brain.
1971;94:165–72.
23. Valko PO, Gavrilov YV, Yamamoto M, et al. Damage to histaminergic
tuberomammillary neurons and other hypothalamic neurons with trau-
matic brain injury. Ann Neurol. 2015;77:177–82.
24. Shekleton JA, Parcell DL, Redman JR, Phipps-Nelson J, Ponsford JL,
Rajaratnam SM. Sleep disturbance and melatonin levels following trau-
matic brain injury. Neurology. 2010;74:1732–8.
25. Nardone R, Bergmann J, Kunz A, et al. Cortical excitability changes in
patients with sleep-wake disturbances after traumatic brain injury.
J Neurotrauma. 2011;28:1165–71.
26. Chaudhuri A, Behan PO. Fatigue in neurological disorders. Lancet.
2004;363:978–88.
27. Kohl AD, Wylie GR, Genova HM, Hillary FG, Deluca J. The neural cor-
relates of cognitive fatigue in traumatic brain injury using functional
MRI. Brain Inj. 2009;23:420–32.
28. Rao V, Spiro J, Vaishnavi S, et al. Prevalence and types of sleep distur-
bances acutely after traumatic brain injury. Brain Inj. 2008;22:381–6.
29. Gosselin N, Lassonde M, Petit D, et al. Sleep following sport-related con-
cussions. Sleep Med. 2009;10:35–46.
30. Tkachenko N, Singh K, Hasanaj L, Serrano L, Kothare S. Sleep disorders
associated with mild traumatic brain injury using sport concussion assess-
ment tool 3 (SCAT-3). Pediatr Neurol. 2016;57:46–50.e1.
31. Sabharwal P, Mahmoudi M, Berberi N, Vasquez BA, Friedman D, Kothare
SV. A case of recurrent insomnia: extending the spectrum of autoimmune
encephalitis. J Clin Sleep Med. 2016;15(5):763–5.
32. Singh K, Morse AM, Tkachenko N, Kothare S. Sleep disorders associated
with traumatic brain injury—a review. Pediatr Neurol. 2016;60:30–6.
33. Williams BR, Lazic SE, Ogilvie RD. Polysomnographic and quantitative
EEG analysis of subjects with long-term insomnia complaints associated
with mild traumatic brain injury. Clin Neurophysiol. 2008;119:429–38.
34. Schreiber S, Barkai G, Gur-Hartman T, et al. Long-lasting sleep patterns
of adult patients with minor traumatic brain injury (mTBI) and non-mTBI
subjects. Sleep Med. 2008;9:481–7.
35. Frieboes RM, Muller U, Murck H, von Cramon DY, Holsboer F, Steiger
A. Nocturnal hormone secretion and the sleep EEG in patients several
months after traumatic brain injury. J Neuropsychiatry Clin Neurosci.
1999;11:354–60.
36. Parcell DL, Ponsford JL, Redman JR, Rajaratnam SM. Poor sleep quality
and changes in objectively recorded sleep after traumatic brain injury: a
preliminary study. Arch Phys Med Rehabil. 2008;89:843–50.
37. Benca RM. Diagnosis and treatment of chronic insomnia: a review.
Psychiatr Serv. 2005;56:332–43.
38. Menn SJ, Yang R, Lankford A. Armodafinil for the treatment of excessive
sleepiness associated with mild or moderate closed traumatic brain injury:
a 12-week, randomized, double-blind study followed by a 12-month open-
label extension. J Clin Sleep Med. 2014;10:1181–91.
39. Sack RL, Auckley D, Auger RR, et al. Circadian rhythm sleep disorders:
part II, advanced sleep phase disorder, delayed sleep phase disorder, free-
running disorder, and irregular sleep-wake rhythm. An American Academy
of Sleep Medicine review. Sleep. 2007;30:1484–501.
40. Dams-O'Connor K, Spielman L, Singh A, et al. The impact of previous
traumatic brain injury on health and functioning: a TRACK-TBI study.
J Neurotrauma. 2013;30:2014–20.
41. Giacino JT, Whyte J, Bagiella E, et al. Placebo-controlled trial of amanta-
dine for severe traumatic brain injury. N Engl J Med. 2012;366:819–26.
42. Centers for Disease Control and Prevention. What can I do to help feel
better after a mild traumatic brain injury? 2016. http://www.cdc.gov/trau-
maticbraininjury/recovery.html. Accessed 30 Mar 2016.
43. Jones KB, Wilson B, Weedon D, Bilder D. Care of adults with intellectual
and developmental disabilities: traumatic brain injury. FP Essent.
2015;439:31–41.
44. Salti R, Tarquini R, Stagi S, et al. Age-dependent association of exposure
to television screen with children's urinary melatonin excretion? Neuro
Endocrinol Lett. 2006;27:73–80.
45. Gooley JJ, Chamberlain K, Smith KA, et al. Exposure to room light before
bedtime suppresses melatonin onset and shortens melatonin duration in
humans. J Clin Endocrinol Metab. 2011;96:E463–72.
Index
A B
Adaptive Behavioral Assessment Body mass index (BMI), 120
System, 2nd Edition Brain tumor, 4, 139–145
(ABAS-II), 144 cognitive testing
Adenotonsillectomy, 46, 48–52, 54, academic achievement and
56, 57 functioning, 141
ADs. See Arousal disorders (ADs) adaptive functioning,
AHI. See Apnea/hypopnea index 144–145
(AHI) behavioral observations, 140
American Academy of executive functioning and
Otolaryngology-Head attention, 142–144
and Neck Surgery intellectual functioning,
(AAO-HNSF), 48 140–141
American Academy of Pediatrics learning and memory,
(AAP), 48 142, 143
American Academy of Sleep verbal fluency, 141, 142
Medicine (AASM), 13, 48 craniopharyngioma
Anemia, 37 (see Craniopharyngioma)
Anti-glutamic acid decarboxylase EDS, 135, 138
(GAD) antibody follow-up sleep study and
syndrome, 195 subjective sleep
Apnea/hypopnea (AHI) index, ratings, 139
128, 136 MRI, 136, 146
Arousal disorders (ADs), 91 obstructive hydrocephalus, 133
Arousal parasomnias, 173, 176 PSG, 136
Asthma sleep and fatigue, 135
sleep complaints, 121 Bright light therapy, 14, 16, 18
Attention-deficit hyperactivity
disorder (ADHD), 8,
62, 64 C
Autosomal dominant nocturnal CA. See Confusional arousals (CA)
frontal lobe epilepsy, 174 Caffeine, 12, 18–20

in Adolescents, DOI 10.1007/978-3-319-41742-4
204 Index
California Verbal Learning Test, diagnosis and treatment, 150

Children’s Version diagnostic impressions, 145–146
(CVLT-C), 142 follow-up sleep study
Cataplexy, 62–64, 66, 67, 69, 71, and subjective sleep
72, 75, 76 ratings, 139
CBC. See Complete blood count initial sleep study and
(CBC) subjective sleep ratings,
CBT-I. See Cognitive behavioral 136–138
therapy for insomnia scheduled sleep assessments,
(CBT-I) 138–139
Center for Epidemiologic Studies EDS, 133, 149
Depression Scale hypothalamic, 149
(CES-D), 100 low-grade intracranial
Chronic kidney disease (CKD), 36 tumors, 148
Chronic renal failure, 29 objective and subjective sleep
Chronotherapy, 16 assessments, results,
Circadian phase delay, 47 137–138
Circadian rhythm, 11, 12, 14, 16, obstructive hydrocephalus, 135
18, 22
Circadian rhythm sleep-wake
disorders (CRSWD), 9 D
CKD. See Chronic kidney disease Delayed sleep phase disorder
(CKD) (DSPD), 69
CMP. See Comprehensive Delayed sleep-wake phase disorder
metabolic panel (CMP) (DSWPD), 2, 178, 179
Cognitive behavioral therapy bright light therapy, 14, 18
(CBT), 101 caffeine, 12, 20
Cognitive behavioral therapy for cataplexy, 19
insomnia (CBT-I), chronotherapy, 16, 17
158, 168 circadian rhythm, 11, 12
Columbia Suicide-Severity (CSS) EDS, 8
rating scale, 100 melatonin, 13, 16
Complete blood count (CBC), 123 phase advancement schedule, 14
Comprehensive metabolic panel polysomnography, 21
(CMP), 123 sleep history and sleep logs, 9
Confusional arousals (CA), 86, 87 sleep hygiene, 21
Continuous positive airway sleep-related breathing
pressure (CPAP), disorders, 23
51–57, 123 snoring and leg symptoms, 9
OSA, 123, 128, 129 trazodone, 12
thyroid abnormalities, 124 Depression
CPAP. See Continuous positive criteria, depressive disorder, 98
airway pressure (CPAP) description, 95
Craniopharyngioma, 136–139 diagnosis, 100, 101
assessment and intervention DSM-5, 105
schedule, 134 hypersomnia and insomnia, 97, 98
(see also Brain tumors) and PTSD, 4
Index 205
psychiatric disorders, 97, 110 hypersomnia\narcolepsy, 151

screening and monitoring sleep problem, children and
severity, 100 adolescents, 148
sleep measures, 100 symptoms, 149, 151
treatment, 100 Eye movement desensitization and
Diagnostic and Statistical Manual reprocessing (EMDR), 112
(DSM-5), 97
Dim light melatonin onset
(DLMO), 179 F
DISE. See Drug-induced sleep Fatigue
endoscopy (DISE) and EDS, 148
Disorders of arousal, 86, 91 and sleep, 135
Drug-induced sleep endoscopy PedsQL MFS, 138, 139
(DISE), 55–57 questionnaires, 145
DSM-5. See Diagnostic and sleep problems, 138
Statistical Manual symptoms, 147, 151
(DSM-5) Frontal lobe epilepsy and
DSPD. See Delayed sleep phase parasomnias (FLEP), 176
disorder (DSPD)
DSWPD. See Delayed sleep-wake
phase disorder (DSWPD) H
Dysfunctional Beliefs and H1N1 influenza, 71
Attitudes about Sleep Headaches, 126–128, 130
(DBAS-16), 160 Human leukocyte antigen
(HLA), 182
Hypersomnia
E hypocretin/orexin
Ear-nose-throat (ENT), 128 neurotransmitter
EDS. See Excessive daytime system, 194
sleepiness (EDS) posttraumatic, 192
Epilepsy, 5 Hypothyroidism
antiseizure drugs, 183 clinical features, 125
arousal parasomnias, 176 OSA, 123, 130
DSWPD, 178–179 sleep apnea, 124
EEG and polysomnography, 177 treatment of, 124
JME, 177, 179–180, 183
narcolepsy, 182
NFLE, 174, 176 I
nocturnal seizures, 173 ICSD-3. See International
parasomnia, 175–176 classification of sleep
Epworth sleepiness scale (ESS), 126 disorders (ICSD-3)
ESS. See Epworth sleepiness Insomnia, 5, 98
scale (ESS) anxiety and depression, 127
Excessive daytime sleepiness case study, 164–168
(EDS), 8 CBT-I, 158, 168
brain tumors, 149 cognitive restructuring, 160, 163
craniopharyngioma, 148 DBAS-16, 160
206 Index
Insomnia (cont.) OSA, 123

diagnostic interview, clinical RLS, 127
case, 156–158 Melatonin, 13, 16, 18, 23
electronic media usage, 166 Migraine headaches, 125–127
excessive daytime Morbid obesity, 49
sleepiness, 165 Multiple sleep latency test (MSLT),
irregular sleep/wake 63, 69, 182
disorder, 158
medical and psychiatric
disorders, 168 N
melatonin levels and circadian Napping, 158, 161, 165, 167, 168
rhythms, 160 Narcolepsy, 3, 5
melatonin suppression, 167 ADHD, 62
napping, 161 anti-cataplectic medications, 72
3P model, 166 attacks, cataplexy, 63
sleep log, 158, 161 cataplexy, 63, 66, 71
sleep problems, 156, 165 diagnosis, 64, 187
sporadic napping, 165 epilepsy, 182
symptoms, 165 excessive daytime sleepiness, 187
visual imagery and H1N1 virus infection, 70
diaphragmatic breathing medications, pregnancy
techniques, 161, 162 classification, 73–74
International classification of sleep MSLT, 63, 69, 182
disorders (ICSD-3), orthostasis, 69
83, 86 Pandemrix vaccination, 70
Irregular sleep/wake disorder, 158 polysomnogram and multiple
sleep latency, 69
pregnancy, 72
J PSG and MSLT, 70, 151
JME. See Juvenile myoclonic psychosocial screening
epilepsy (JME) questions, 74–75
Juvenile myoclonic epilepsy (JME) RBD, 66, 67
broad spectrum antiepileptic REM, 67
drugs, 180 safe sleep environment, 67
diagnosis, 182 sleep disorders, 193
epilepsy syndrome, 179, 182 SOREM, 62
excessive sleepiness, 181 symptom directed screening
OSA, 180 questions, 65, 66, 148
seizure types, 180 testing results, 69
tonic–clonic seizures, 179 National Comorbidity Survey
Replication (NCSR),
106–107
M NES. See Night eating syndrome
Medical disorders (NES)
asthma, 120 NFLE. See Nocturnal frontal lobe
CPAP, 124 epilepsy (NFLE)
Index 207
Night eating syndrome (NES), 84, 85 NES, 84

N-methyl-D-aspartate (NMDA) NFLE, 88
receptor antibodies, 191 night terrors, 88
Nocturnal cramps, 31, 33, 35 NREM parasomnia, 87
Nocturnal frontal lobe epilepsy OSAS, 84
(NFLE), 88, 174 polysomnogram, 82
Nocturnal myoclonus, 31, 32, 35 pramipexole, 85
Nocturnal seizures, 173 RBD, 80
RLS, 84
sleep terrors, 82
O SRED, 83, 85
Obesity, 48, 51 SSRI, 81, 84
Obesity hypoventilation SW, 88
syndrome, 52 SWS, 87
Obstructive sleep apnea syndrome Patient Health Questionnaire
(OSAS), 3, 84, 85 (PHQ-9), 96
adenotonsillectomy, 46, 48, Pediatric Quality of Life
49, 51 Multidimensional
airway obstruction, 56 Fatigue Scale
bariatric surgery, 52 (PedsQL MFS), 138
circadian phase delay, 47 Periodic limb movements of sleep
clinical features, 125 (PLMS), 63, 67, 83, 85,
comorbid circadian, 49 90, 193
CPAP, 51, 52, 123, 129 and RLS, 129
diagnosis, 50 Pharmacological interventions, 148
DISE, 55, 56 PLMS. See Periodic limb
excessive daytime sleepiness, 47 movements of sleep
features, 47 (PLMS)
high risk factors, 49, 50 Polysomnography (PSG), 70
hypertrophic lymphoid tissue, 51 Posttraumatic stress disorder
hypothyroidism, 124, 125, 130 (PTSD)
obesity hypoventilation assessment of adolescent, 109
syndrome, 52 case study, 105–106
pathophysiology, 51 diagnosis, 110
perioperative complications, 55 DSM—5 criteria, 107–108
polysomnography, 46, 55, 123 insomnia and trauma-related
REM-dominant, 54 nightmares, 112
troubleshooting, CPAP, 53 Prazosin, 112
weight loss, 54 sleep disturbances, 112
symptoms, 106, 109
trauma-focused
P psychotherapies, 112
Parasomnias, 4, 174–176 traumatic events, 106, 109
CA, 86–88 Primary care PTSD screen
disorders of arousal, 91 (PC-PTSD), 110, 111
ICSD-3, 83 PSG. See Polysomnography (PSG)
208 Index
Psychiatric disorders Sleep disorders

adolescent depression, 97 assessment of, 195–196
comorbid, 109, 110 impaired cognitive impairment,
193
management, TBI, 196–198
R (see Posttraumatic stress
Rapid eye movement (REM) sleep, disorder (PTSD))
67, 196 sleep fragmentation, 192
RBD. See REM behavior disorder TBI, 188, 194
(RBD) Sleep disturbances
REM. See Rapid eye movement asthma, 120–122
(REM) concurrent allergic
REM behavior disorder (RBD), 66 rhinitis, 122
Restless legs syndrome (RLS), 3, depression and fibromyalgia, 127
84, 85 Sleep hygiene, 21, 22
anemia, 30 Sleep log, 158, 161, 165, 168, 169
chronic renal failure, 29 Sleep onset REM (SOREM), 63,
CKD, 36, 40 69, 136, 145
depressed mood and emotional Sleep terrors (ST), 82, 86, 88
instability, 30 Sleep-onset insomnia, 2
diagnosis, 31 Sleep-related eating disorder
dopaminergic therapy, 35, 129 (SRED), 83, 86
ferritin and folic acid levels, 31 Sleepwalking (SW), 82, 84, 86,
ferritin levels, 37 88, 91
growing pains, 27 Slow wave sleep (SWS), 86, 87
iron deficiency, 29 Smith Magenis syndrome, 81
medications, treatment, 39 SOREM. See Sleep onset REM
mimics, adolescents SSRI, (SOREM)
32–35 SSRI. See Selective serotonin
neurologic sensorimotor reuptake inhibitor (SSRI)
disorder, 28 SW. See Sleepwalking (SW)
nocturnal cramps, 31
nocturnal myoclonus, 31, 35
pathophysiology, 29 T
pharmacologic agents, 37 Teenagers
polysomnography, 28 sleep disorder, 2
potential sleep problems, 38 Thyroid peroxidase (TPO), 123
prevalence of migraine, 127 Thyroid-stimulating hormone
serum ferritin, 29, 30 (TSH), 123
sleep disorder, 38 TPO. See Thyroid peroxidase
(TPO)
Trauma-focused cognitive-
S behavioral therapy
Selective serotonin reuptake (TF-CBT), 112
inhibitor (SSRI), 35, Traumatic brain injury (TBI),
80–82, 84 195–198
Sleep deprivation, 126, 127 actigraphy, 195
Index 209
autoimmune encephalitis transcranial magnetic

(AE), 194 stimulation, 194
EDS, 193 Traumatic brain injury
MSLT, 196 (TBI), 5
PLMS, 193 Treatment for Adolescents with
posttraumatic hypersomnia, Depression Study
190–192 (TADS), 101
posttraumatic narcolepsy, Treatment of Resistant Depression
187–188 in Adolescents
sleep disorders (TORDIA), 101
assessment, 195–196 TSH. See Thyroid-stimulating
management, 196–198 hormone (TSH)
treatment, 197
mechanisms, 193–195
sleep hygiene, 189–190 V
sleep problems, 196 Voltage gated potassium
striatal-thalamic-frontal cortical channelopathy (VGKC),
system, 194 195

Sanjeev V. Kothare, Rebecca Quattrucci Scott (Eds.) - Sleep Disorders in Adolescents - A Clinical Casebook-Springer International Publishing (2017)

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Sanjeev V. Kothare, Rebecca Quattrucci Scott (Eds.) - Sleep Disorders in Adolescents - A Clinical Casebook-Springer International Publishing (2017)

Uploaded by

Copyright:

Available Formats

Sanjeev V.

ISBN 978-3-319-41741-7 ISBN 978-3-319-41742-4 (eBook)

Library of Congress Control Number: 2016950520

© Springer International Publishing Switzerland 2017

Printed on acid-free paper

This Springer imprint is published by Springer Nature

New York, NY, USA Sanjeev V. Kothare

11 Epilepsy and Sleep in Adolescents .............................. 173

Index ...................................................................................... 203

Vicky Chiang, B.S. Department of Neurology, New York

Umakanth A. Khatwa, M.D. Division of Respiratory Diseases,

It is a known fact that sleep is vital for physical, cognitive and

S.V. Kothare, M.D. (*) • R. Quattrucci Scott, Ph.D.

© Springer International Publishing Switzerland 2017 1

As with adults, inadequate sleep in teenagers has signiﬁcant and

length. Comprehensive evaluation and treatment plans, including the

Chap. 6 reviews three cases of either non-REM or REM

following a pharmacological intervention for his narcolepsy are

AASM American Academy of Sleep Medicine

S.D. Jaquez, Ph.D.

© Springer International Publishing Switzerland 2017 7

EDS Excessive daytime sleepiness

Hannah is a 17-year-old female presenting to the sleep clinic with

with an inability to initiate sleep at a socially acceptable time at

Fig. 2.2 Sample actigraphy chart. An actigraphy is a wrist watch-like device

• DSWPD is a relatively common disorder that is frequently

• If excessive daytime sleepiness is a chief compliant, sleep logs

Andrew is a laconic 15-year-old male who presents with his mother

low-dose melatonin and morning exposure to sunlight. His mother

While several case reports have documented the effectiveness of

Table 2.1 Sample phase advancement schedule

Time Relative to Baseline DLMO (h)

gland in a well-deﬁned 24-h cycle. During the daytime, levels of

light exposure. It should be noted that light exposure at the wrong

• Often an erroneous diagnosis of insomnia or hypersomnia is

Endogenous Melatonin Level

Normal sleep time

Table 2.2 Sample phase delay schedule (chronotherapy)

• Westward travel may be transiently favorable for patients with

Carmen is an 18-year-old female presenting to the sleep clinic

Despite being a borderline obese teenage girl, Carmen’s physi-

Although Carmen presents with symptoms similar to DSWPD, the

signiﬁcant lack of knowledge about caffeine content of common

• Caffeine use can mask sleep-speciﬁc concerns, either by caus-

• Caffeine and other psychostimulants can result in delayed sleep

Zachary is a 10-year-old male presenting to the sleep clinic with

with her parents and occupying the unﬁnished basement. She

In Zachary’s case, sleep-related breathing disorders needed to ﬁrst be

• Poor sleep hygiene can mimic DSWPD.

• Sleep hygiene interventions are a useful part of all sleep-related

DSWPD involves a persistent and signiﬁcant phase shift in sleep-

sleep-related breathing disorders. A comprehensive sleep history

CKD Chronic Kidney Disease

Stephanie is a 14-year-old young woman who presents to clinic

© Springer International Publishing Switzerland 2017 27

Stephanie was likely misdiagnosed with growing pains during

age range, RLS remains frequently unrecognized, misdiagnosed,

enhance iron absorption. Iron studies should be done every 3 months

• A strong relation between body iron stores and the severity of

• Treatment with oral iron is recommended with serum ferritin

Mark is a 17 year-old young man who initially presented to the

school performance. Mark states that he goes to bed around 10 pm,

The diagnosis of RLS is based on the presence of clinical diagnos-