Case Series
A Case Based Approach to Evaluation and Management of Simple and Mixed Disorders of Sleep
Alexandre R Abreu and Alejandro D Chediak*
Department of Medicine-Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of Miami
Miller School of Medicine, USA
*Corresponding author: Alejandro D Chediak, Department of Medicine-Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of Miami Miller School of Medicine, P.O. Box 016960 (D-60) Miami, Florida 33101, 305-243-9999, USA
Published: 07 Jul, 2017
Cite this article as: Abreu AR, Chediak AD. A Case
Based Approach to Evaluation and
Management of Simple and Mixed
Disorders of Sleep. Ann Clin Case Rep.
2017; 2: 1394.
Abstract
Sleep apnea is a common respiratory disorder of sleep which when untreated or inadequately treated has profound adverse effect on behavioral, metabolic and cardiovascular health outcomes. Breathing disturbances of sleep may be characterized as obstructive, central, mixed or a complex combination were both central and obstructive breathing disturbances of sleep coexist. In cases with high clinical index of suspicion for isolated moderate to severe obstructive sleep apnea, the diagnosis and optimal treatment can be delivered with a traditional laboratory approach or with domiciliary tools. However, many cases of sleep apnea are multifaceted or overlap with other disturbances of sleep, rendering such cases challenging to diagnose and manage thereby necessitating comprehensive assessment in an accredited sleep laboratory. Rather than treat individual disorders of sleep and breathing out of context with clinical practice, this manuscript aims to present real-life clinical cases that facilitate the discussion and education pertaining to the evaluation and management of selected disorders of sleep and breathing.
Introduction
Sleep can be considered rapidly alternating, naturally occurring behavioral state where the
brain dissociates from the environment. For many years, the principle medical concern pertaining
to sleep was its absence, namely insomnia, and disorders of sleep were generally considered rare,
infrequently studied and, therefore, poorly understood. The past several decades has seen an upsurge
in sleep research with parallel growth in clinical sleep disorders as a unique discipline of medicine.
The third edition of the International Classification of Sleep Disorders (ICDS-3) [1] describes over 90 distinct disorders of sleep and it is not uncommon for two or more distinct disorders of sleep to
coexist in one subject [2].
The term Sleep Disordered Breathing (SDB) encompasses several respiratory disturbances
of sleep including Obstructive Sleep Apnea (OSA), Central Sleep Apnea (CSA) and sleeprelated
hypoventilation syndromes. Of these, OSA is the most common with prevalence, in one
population study, estimated to be 14% in men and 5% in women [3]. In selected populations, the prevalence of OSA can be considerably higher, approaching 80% and 70% in bariatric surgery and
ischemic cerebrovascular disease populations, respectively [4,5]. OSA sufferers are often sleepy during the day, manifest cognitive impairment and are at increased risk for developing metabolic
derangements, and cerebrovascular and cardiovascular disease including, coronary artery disease,
difficult to control hypertension, arrhythmias and stroke [6-8]. Using cost data from the year prior to the diagnosis of SDB, Kapur [9] and colleagues reported a mean annual medical cost savings of $1336 (49% reduction) per case compared to age and gender matched controls. Further, they
estimate that in the United States, untreated sleep apnea may add $3.4 billion in medical costs.
Diagnosing SDB requires the measurement of breathing during sleep. ICSD-3 defines OSA as a
polysomnography (PSG) derived obstructive respiratory disturbance index (RDI) ≥ 5 events/hour
associated with symptoms or an obstructive RDI ≥ 15/hour in the absence of symptoms [1]. The RDI is derived by the sum of all apneas, hypopneas and respiratory effort related arousals (RERA)
divided by the number of hours of sleep while the apnea hypopnea index (AHI) is similar with the
exception of the exclusion of RERA events from the calculation. There is general consensus on the
definition of apnea. However, the criteria for identifying hypopnea are not uniform [10]. Hypopnea can be scored if associated with either a cortical arousal in the sleep EEG or a non-artefactual decline
in oxyhemoglobin saturation by 3% to 4%. In this manuscript, all case specific indices of breathing
required a 4% decline in oxyhemoglobin saturation as prerequisite for identifying hypopnea.
OSA is a potentially life-threatening disorder that may be
comorbid with a secondary sleep disturbance or masquerade as
another sleep disorder [2,11]. Therefore, it follows that, when OSA
is suspected, a comprehensive sleep evaluation and appropriate
diagnostic testing is necessary to address OSA along with any possible
comorbid sleep disturbances. This narrative aims to highlight
the evaluation and management of SDB with cases illustrative of
uncomplicated isolated OSA and OSA complicated by another sleep
disorder, specifically CSA and narcolepsy.
Table 1
Case 1
History and clinical features
OS presented to the sleep specialist as a 55-year-old male with
disruptive snoring, spouse observed apnea and Excessive Daytime
Sleepiness (EDS). Onset and severity of symptoms correlated with
a 50-pound weight increase over the preceding 2 years. Prior to the
weight increase, he neither snored loudly nor complained of EDS.
Hypersomnia was severe as evidenced by 2 episodes of unintended
dozing while driving. The Epworth Sleepiness Scale score [12] was 12
in the light of 8 hours of reported sleep per night on workdays and 10
hours on days off. Increasing the opportunity for sleep at night and
daytime sleep was not helpful at alleviating EDS.
Salient features on physical examination include a body mass
index of 36.8 kg/m2, neck circumference of 17.5 inches, blood
pressure 154/103 mmHg and oxyhemoglobin saturation of 97%
while at rest and breathing room air. The oral pharyngeal aperture
is Mallampati class 3 [13] with scalloping of the tongue, narrowing
of the maxilla and marked enlargement of the uvula and soft palate.
The maxillary overjet was 1 mm. The STOP BANG [14] score was 8, a
value predictive of moderate to severe OSA. As the presentation was
characteristic for OSA, a home sleep apnea test (HSAT) was deemed
appropriate [15,16].
HSAT was performed with a device meeting criteria for a type III
monitor [15]. The recording, consisting of 7 hours and 11 minutes of
artifact free data, shows AHI of 40 and oxyhemoglobin saturation was
below 90% during 9% of the recording. After a session of education
and positive airway pressure (PAP) therapy mask fitting, Automatic
Positive Airway Pressure (APAP) was prescribed.
On follow-up, 30 day mean daily utilization of positive airway
pressure therapy was 6 hours and 39 minutes and APAP was used
for 4 hours or more on 80% of days. The apnea plus hypopnea index
(AHI) on APAP was 3.3 indicating optimal control of OSA [17].
APAP treatment of obstructive sleep apnea completely controlled
disruptive snoring, spouse observed apnea and normalized diurnal alertness. The 6-week posttreatment Epworth sleepiness scale score was 4 and systemic blood pressure had decreased to 140/87 mmHg
without weight reduction or resorting to pharmaceutical intervention.
Discussion
This case represents the characteristic presentation of a patient
with increased risk of moderate to severe OSA in an individual without
clinically relevant comorbid conditions that might otherwise degrade
the accuracy of HSAT [15,16,18]. Among randomized control trials
comparing an at home versus in laboratory paradigm that most closely
approximates clinical circumstances for the diagnosis and treatment
of OSA, the clinical definition of increased risk for moderate to severe
OSA varies [19-22]. However, the 2017 clinical practice guideline for
diagnostic testing for adult sleep apnea from the American Academy
of Sleep Medicine (AASM) [16] promotes the notion that increased
risk for moderate to severe OSA can be defined as EDS on most days
plus the presence of at least 2 of the 3 following criteria: habitual
loud snoring; witnessed apnea or gasping or choking; or diagnosed
hypertension.
HSAT is less sensitive than PSG for detection of OSA. Employing
Type 3 HSAT devices and using an AHI ≥ 5 cut off for diagnosing
OSA, Kapur and company [16] calculated HSAT accuracy in a
high risk population ranges from 84% to 91% whereas in a low risk
population, accuracy ranges from 70% to 78%. Similar analysis using
an AHI ≥ 15 and AHI ≥ 30 cut off in a high-risk population estimates
accuracy of 65% to 91% and 88%, respectively. A false-negative HSAT
can lead to significant harm. Considering the afore mentioned and
given that repeat HSAT is unlikely to change diagnostic outcome, a
single negative, inconclusive or technically inadequate HSAT should
be followed by PSG.
Continuous positive airway pressure (CPAP) therapy after
titration with attended PSG in the sleep laboratory has long been
considered the standard of care for treating OSA. Technological
advance has fostered PAP devices capable of assessing breathing
patterns and responding to impending respiratory instability by
modifying their output. Collectively known as APAP technology,
these devices are purported to auto-adjust and control OSA thereby
obviating the need for titration polysomnography. In properly
selected patients treated by sleep experts, APAP titration yields
treatment settings and clinical outcomes similar to that derived using
CPAP with setting based on attended laboratory titration [19,21,22].
However, not all APAP devices sense or respond to breathing with
similar algorithm and device accuracy should be considered device
dependent. Outcomes of OSA treated with PAP have been shown to
be superior when delivered by board-certified sleep specialist and/or
in facilities accredited by the AASM [23-25]. It is, therefore, advisable
for PAP management to be directed by the sleep specialist or through
an AASM credential facility equipped with a PAP management
program.
Key learning points
1. OSA often occurs in the context of obesity and weight
increase [26].
2. Inappropriately selected uncomplicated cases of OSA
managed by a sleep specialist, HSAT can reliably diagnose OSA and
produce outcomes similar to that using a paradigm that involves PSG
for diagnosis and adjustment of PAP therapy [19,21,22,27].
3. APAP treatment of uncomplicated OSA is an acceptable
alternative to CPAP and may obviate the need for CPAP titration
PSG [18,19,21,22,28].
4. Treatment utilization by an objective means is an important
outcome metric [29,30].
5. Follow up in a sleep specialty clinic with physician
credentialing in sleep medicine and/or AASM facility credentialing
may improve outcomes in OSA treated with PAP [23,25].
Table 2
Table 3
Case 2
History and clinical features
OF is a 69-year-old male referred to the sleep specialist in Miami,
Florida by his cardiologist in the evaluation of suspected OSA.
The syndrome was considered because of EDS (Epworth 14), loud
snoring, hypertension and atrial fibrillation. Additionally, insomnia,
described as hourly awaken to void his urinary bladder plus, about
3-4 times per week, prolonged awakenings after nocturia. Selfreported
sleep duration was 6-9 hours on nights without prolonged
awakenings and less than 4 hours on nights when nocturia was
followed by prolonged awakening. His medical history was positive
for hypertension, diabetes, chronic kidney disease and recent onset
atrial fibrillation. OF has ceased smoking cigarettes at age 35 years,
consumed only one decaffeinated coffee in the morning and less than
1 alcoholic beverage per month. Opiates were not being used. The
family history was negative for disorders of sleep.
Salient features on physical examination include a BMI of 29.5
kg/m2. Neck circumference was 18.75 inches and the oral pharyngeal
appearance is Mallampati class 3 with thick tongue, enlarged soft
palate and a wide and slightly long uvula. Maxillary overjet is 0 mm -
1 mm. Examination of the heart was remarkable for irregular rhythm.
The STOP BANG [14] score was 6, a value predictive of moderate to
severe OSA. Recent onset atrial fibrillation, chronic kidney disease
and insomnia prompted a recommendation for attended PSG over
HSAT. PSG with both diagnostic and therapeutic components (split
night) was ordered.
Split-night PSG confirmed sleep apnea with AHI 53.7 and RDI
54.4. However, central apnea index was 14 on the diagnostic portion
of the PSG and on the therapeutic portion with application of CPAP,
obstructive events were abolished but CSA persisted with central apnea
index (CAI) of 60 on CPAP. Cardiac rhythm was atrial fibrillation. His
final sleep diagnosis was severe obstructive and treatment emergent
CSA. After confirmation of left ventricular ejection fraction > 45%,
PSG for titration of adaptive servo ventilation (ASV) PAP technology
was conducted. The ASV titration PSG confirmed optimal control of
obstructive and central sleep apnea events.
Domiciliary treatment with ASV led to resolution of nocturia,
prolonged awakenings and improvement in EDS (post treatment
Epworth 2). On follow-up, 180 day mean daily utilization of positive
airway pressure therapy was 5 hours and 42 minutes and APAP was
used for 4 hours or more on 80% of days. The AHI on APAP was 0
indicating optimal control of OSA [17].
Discussion
The patient has EDS, hypertension and loud snoring, clinical
features consistent with increased risk for moderate to severe OSA
as similarly described on the earlier case. However, the presence of
clinically significant comorbid cardiovascular disease and insomnia
render the case unsuitable for HSAT [15,16]. The presence of atrial
fibrillation increases the probability for concomitant CSA [31], a
respiratory arrhythmia where HSAT has not been suitably validated as
a means to establish the diagnosis [16]. Hence, PSG is the appropriate
diagnostic intervention. Indeed, had HSAT been conducted, he
would have required attended PSG for confirmation of CSA.
ICDS-3 [1] identifies 8 distinct types of CSA syndromes of which
2 are unique to infancy and prematurity. CSA with Cheyne-Stokes
breathing, CSA due to a medical disorder without Cheyne-Stokes
breathing (CSB), CSA due to high-altitude, CSA due to medication
or substance (i.e. opiates), primary CSA and treatment emergent
CSA are the purported adult forms of CSA. In this instance, CSA with
CSB, a form of crescendo decrescendo breathing most often seen in
patients with systolic or diastolic heart failure, high altitude CSA,
and medication related CSA can be excluded from the differential
diagnosis. Treatment emergent CSA, primary CSA and CSA due to a
medical disorder without CSB are the more likely CSA subtypes. CSA
attributed to medical disorder without CSB often occurs in the context
of severe neurologic disease with brainstem lesions, the breathing
pattern can be ataxic, and afflicted individuals can have diurnal and/
or nocturnal hypoventilation, features lacking in this case. Primary
CSA patients have a higher incidence of atrial fibrillation, but so do
patients with OSA, the latter as was diagnosed by PSG. Hence, CSA
in this instance is most representative of treatment emergent CSA.
Some use the term "complex sleep apnea" to identify cases was
OSA and CSA coexist. As used by some clinicians, the terminology
makes no distinction of CSA causality and as such is inherently vague
[32]. Nonetheless, the term continues to be used but with increasing
frequency to describe CSA and OSA occurring in the context of PAP
treatment of OSA [33,34]. The pathogenesis of treatment emergent
CSA is not well understood and may involve dual effects of anatomic
and physiologic vulnerability to OSA plus respiratory control
instability with enhancement of loop gain [35]. Maladaptation to
PAP with repeated arousals and sleep-onset central apneas and
activation of the inspiratory inhibitory component of the Hering-
Bruer reflex [36] are other proposed pathophysiologic mechanisms
of treatment emergent CSA, the latter consistent with the clinical
observation that treatment emergent CSA seems to be more common
in patients requiring higher levels of PAP. To the extent that one or
more of these mechanisms are involved in a given case is unknown.
However, in this instance the presence of CSA prior to the application
of CPAP suggests high loop gain was involved in the pathogenesis of
his treatment emergent CSA.
Treatment emergent CSA occurs in approximately 6% - 10%
of CPAP titration polysomnograms [37,38]. However, treatment
emergent central sleep apnea can be transitory and resolve with 2-3
months of continued CPAP treatment in all but about 2% - 8% of
cases [38,39].
The treatment of CSA syndromes in adults is based on the
underlying mechanism [40]. The science to support specific therapies
is limited and that which is available is based on case series, small
randomized trials with surrogate endpoints and a handful of
randomized controlled trials largely limited to patients with both
OSA and CSA. Table 1 list the evidenced based CSA subtype specific
therapeutic alternatives as advanced by the AASM in the 2012 and
2016 Practice Parameters for the treatment of central sleep apnea in
adults [40,41]. In Table 2 we list other therapeutic interventions of reported benefit in the treatment of CSA.
Key learning points
1. CSA can occur with and without with OSA.
2. The clinical circumstance when relevant numbers of central
apnea coexist with obstructive apnea has been termed complex sleep
apnea [34,38].
3. Complex sleep apnea at sea level is most often seen in
the context of heart failure (with and without preserved EF), atrial
fibrillation-flutter, opiate treatment and as a secondary effect of PAP
therapy of OSA. In this case, CSA was confirmed to present prior to
the application of PAP therapy, worsened on PAP and occurs in the
context of preserved EF. Therefore, the most likely explanation is
either treatment emergent CSA or atrial fibrillation cardiac rhythm
related CSA.
4. CPAP therapy is not universally effective for CSA.
5. In appropriately selected patients with CSA, ASV therapy
can be effective at normalizing AHI and alleviating sleep apnea
symptoms [41].
Case 3
History and clinical features
DA is female first seen when she was 24 years old and presented
with spontaneous onset of irresistible EDS with onset at age 21
years. EDS manifested as unintended dozing while studying and
when driving. She reported hypnagogic hallucinations but not
sleep paralysis and cataplexy. Dream recall was regular, vivid and
sometimes accompanied daytime sleep. EDS occurs despite selfreported
sleep duration of 8 hours per night plus twice weekly 30-45
minute naps and sleeps efficiency of 95%. Her boyfriend described
snoring and witnessing apnea. DA’s past medical and surgical history was unremarkable. Alcohol was consumed at a rate of 6 cocktails per week and she used 2 cans of caffeinated soda daily. There is no
history of illicit drug use. She did smoke 1 cigarette per day, a habit
she acquired at age 20 years. Her family history was remarkable for
OSA in her father.
Salient features on physical examination include a neck
circumference of 14 inches with body mass index (BMI) of 27 kg/m2.
The appearance of the oral pharyngeal airway is Mallampati class II
with +3 tonsils and normal uvula and tongue. The maxillary overjet is
1 mm. The STOP BANG questionnaire score was 3, a value predictive
of OSA [14].
OSA was suspected and diagnostic PSG was ordered but was
negative for OSA. An investigation for a primary central hypersomnia
syndrome followed. Her sleep logs showed stability and sleep-wake
pattern with average time in bed 8.5 hours per night. PSG consisted of
437 minutes of sleep of which 25% was REM. The REM sleep latency
was 4 minutes, consistent with a sleep onset REM period (SOREM).
Nearly the entire recording was conducted when she was in the supine
position. AHI and RDI was 2 and 3, respectively. Oxyhemoglobin
saturation nadir was 96%. Periodic limb movement index was 1.
Multiple sleep latency test (MS LT) conducted on the day following
PSG had mean sleep latency of 3.9 minutes and 4 SOREM in a 5 nap
protocol, findings consistent with narcolepsy as the cause of her EDS
[42]. Treatment with alertness promoting substances proved effective
at controlling symptoms until 8 years later when DA presented with
worsening hypersomnia despite using methylphenidate at doses that
had typically been fully effective. Her BMI was now 33.7 kg/m2 and
snoring was said to be louder and more disruptive. Reassessment
with diagnostic PSG was diagnostic of OSA with an AHI 8, RDI 29
and oxyhemoglobin saturation nadir of 90%. Subsequent PSG for
titration of PAP confirmed control of OSA with PAP and domiciliary
treatment with PAP restored subjective alertness without requiring
an increase in the dose of methylphenidate.
Discussion
DA presented with EDS, loud snoring and witnessed apnea,
features that are consistent with increased risk of moderate to severe
OSA [16] making HSAT or PSG appropriate for diagnosis. However,
full night attended diagnostic PSG was not diagnostic of sleep apnea.
An evaluation for a primary central hypersomnia syndrome is
warranted in cases where EDS is clinically relevant and the diagnostic
PSG fails to confirm sleep apnea [43,44].
Components of REM sleep occurring while awake and in sleep
transitions such as hypnagogic and hypnopompic hallucinations,
sleep paralysis, and cataplexy are collectively termed dissociated
REM sleep phenomena. Of these, cataplexy is nearly pathognomonic
of narcolepsy but all occur more often in EDS caused by narcolepsy
than in other causes of EDS. DA did not have cataplexy but there
were clinical features consistent with hypnagogic hallucinations and
she manifested vivid dreaming and dreaming during naps, features
suggesting increased REM pressure and favoring narcolepsy as a
potential cause of EDS.
EDS can be quantified by the use of the MSLT [42] and the
diagnosis of narcolepsy requires fulfillment of specific clinical, PSG
and MSLT (Table 3) criteria or the demonstration of cerebral spinal
fluid hypocretin-1 concentration, assayed by immunoreactivity,
that is less than or equal to 110 pg/ml or less than one third of mean
values obtained in normal subjects with the same standardized assay
[1]. MSLT data derived by a standardized protocol was diagnostic of
narcolepsy [45].
ICSD-3 [1] classifies narcolepsy into Type 1 (narcolepsy with
cataplexy) and Type 2 (narcolepsy without cataplexy). Type 1
is prevalent in 0.02% - 0.18% in the US and Western European
populations and in 0.16% - 0.18% in the Japanese populations. The
prevalence of Type 2 disease is not known but estimated to be higher
than that of Type I narcolepsy. Lacking features of cataplexy, DA
was diagnosed with Type 2 narcolepsy and treated with alertness
promoting substances [43] with clinically significant beneficial
effect. Recurrence of EDS occurred in the context of a 25% increase
in BMI and coincides with more disruptive snoring and bed partner
observed apnea. Reassessment with PSG demonstrated moderate
OSA coincident with pre-existing Type 2 narcolepsy. The addition of
PAP therapy restored alertness to normal levels thereby establishing
a causal relationship between the developments of OSA in the
recurrence of EDS.
Key learning points
1. There are numerous causes of EDS such that establishing
a diagnosis can be complex. In the case of DA, the clinical history
on presentation and results of standardized questionnaires were
predictive of OSA. However, irresistible EDS, age of symptom onset,
the occurrence of hypnagogic hallucinations, regular dream recall
and dream recall after naps are atypical features in OSA but not so in
narcolepsy [46].
2. In cases where OSA is likely, an evaluation for a primary
central hypersomnia syndrome cannot proceed without first
excluding OSA or, if OSA is confirmed, controlling OSA with PAP.
The diagnostic hallmark of narcolepsy is the presence of physiologic
sleepiness (mean sleep latency on MS LT ≤ 8 minutes) and ≥ 2
SOREM on MSLT and prior night PSG. Individuals with untreated
OSA can have MSLT findings consistent with narcolepsy [47].
However, in contrast to those with narcolepsy, short sleep latency and
frequent SOREMs in sleep apnea resolves with adequately adjusted
and consistently used PAP therapy.
3. OSA can coexistent and/or complicate existing sleep
disorders as it occurred in this case [2,11].
4. The recurrence of EDS occurred while the patient was
on previously effective doses of alertness promotion therapy and
coincided with significant weight gain and worsening of snoring.
There is a strong relationship between OSA and obesity with
increasing prevalence and severity of OSA with increases in BMI [26].
5. Patient reported questionnaires like the STOP BANG [14]
and others [48], while of value in assessing pretest probability and
severity of OSA, are not sufficient to establish the diagnosis of sleep
apnea [16].
Summary
The previous several decades ushered significant expansion in the study of sleep and its disorders leading to the acceptance of sleep medicine as a formal discipline of medicine. ICSD-3 [1] provides the framework to describe and categorize currently accepted sleep disorders and it further serves to illustrate the diversity of sleep disturbances. In this manuscript, we offer a case based introduction into the diagnosis and management of selected disorders of sleep with emphasis on SDB syndromes.
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