Sleep Disorders: An Algorithmic Approach to Differential Diagnosis

By Hrayr Attarian

This book reviews and discusses the differential diagnoses for the common sleep related complaints encountered in sleep and primary care clinics. It meets the market need for a book that covers differential diagnosis in sleep medicine, and does so in a comprehensive manner.

Organized into two sections by age demographic, adult and pediatric, clinical case studies are presented with medications, treatments, diagnoses, and patient medical histories. Specified sleep disorders examined include insomnia, nocturnal awakenings, restless sleeping, nightmares, and sleep apnea. Additionally, chapters include medical questionnaires created for patients in clinical scenarios to aid in learning.

Unique and pedagogic, Sleep Disorders is written for physicians who practice in all primary care settings and as well as those sleep physicians in training.

• Language: English
• Publisher: Springer
• Release date: Mar 23, 2021
• ISBN: 9783030653026

Book preview

Part IAdult Sleep Medicine

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2021

A. S. Sahni et al. (eds.)Sleep Disordershttps://doi.org/10.1007/978-3-030-65302-6_1

1. Sleepiness

Alok Sachdeva¹  

(1)

Michael S. Aldrich Sleep Disorders Center, Department of Neurology, University of Michigan Health System, Ann Arbor, MI, USA

Alok Sachdeva

Email: [e-mail]

Keywords

SleepinessExcessive daytime sleepinessHypersomnolenceObstructive sleep apneaNarcolepsyIdiopathic hypersomniaMultiple sleep latency test (MSLT)Epworth sleepiness scale

Case 1: Obstructive Sleep Apnea

(Also refer to Chap. 5 , Case 1 for another presentation)

History

A 55-year-old non-obese woman presents to a sleep medicine clinic complaining of sleepiness and fatigue. Shortly after the onset of menopause at the age of 51 years, she noticed decreased daytime energy, which started gradually and progressed slowly. She mentioned this to her primary care physician, who ruled out possible medical causes of fatigue, including hypothyroidism and anemia. Unfortunately, her fatigue persisted, and she eventually developed daytime sleepiness, at times necessitating a mid-day nap. She first noticed daytime sleepiness when recovering from influenza at the age of 53 years, and she initially attributed this symptom to her acute viral illness. When her daytime sleepiness had outlasted other viral symptoms by more than 1 month, she assumed the sleepiness was due to hormonal changes or to a depressed mood, which had been present since her youngest daughter left home for college 1 year earlier.

Differential Diagnosis

Insufficient sleep

Circadian rhythm sleep-wake disorder

Sleep-disordered breathing

Post-viral hypersomnia

Mood disorder

Sleepiness due to a medication/substance

Sleep-related movement disorder

History Continued

The patient’s husband often complains that she snores loudly and is a restless sleeper. In addition, she has awakened from sleep a few times with shortness of breath and gasped for air. When she wakes up in the morning, her mouth is often dry and she sometimes has a sore throat. She wakes up approximately 2–4 times per night for unknown reasons or to urinate, and she can usually fall back asleep quickly. She denies morning headaches.

She denies symptoms consistent with parasomnia or narcolepsy. She also denies symptoms of restless legs syndrome, though she has had intermittent burning pain in her toes on both feet for a few months.

Her depressed mood has improved since sertraline was started about 3 months ago. She also sees a therapist every 6 months. However, she still at times has difficulty falling asleep and may wake up earlier than she would like. A few times per month, she takes diphenhydramine, which helps her fall asleep, but does not improve sleep quality.

Sleep Schedule/Sleep Hygiene

The patient sleeps in a queen-size bed with her husband. They read in bed, but do not use electronics in bed and do not watch television at bedtime. She usually sleeps on her side or her back, and her husband has noticed that she snores more loudly on her back.

Time in bed:

10:30 PM

Lights out:

11:00 PM

Sleep onset latency:

15 minutes; 1–2 times per week, up to 90 minutes

Sleep aids:

Diphenhydramine 25–50 mg a few times per week

Number of awakenings:

3–4 per night

Cause of awakenings:

Unknown, or to urinate

Wake after sleep onset time:

5–10 minutes per awakening

Wake time:

7:30 AM; a few times per week, she wakes at 630 AM

Rise time:

Same as wake time

Naps:

Approximately 2 per week, usually from 1 to 2 PM. Naps are not refreshing.

Total sleep time:

Approximately 7–8 hours per 24-hour period

Scales/Questionnaires

STOP-BANG Scale :

4 points (high risk of obstructive sleep apnea)

Epworth Sleepiness Scale :

13 points (excessive daytime sleepiness)

Fatigue Severity Scale :

37 points (clinically relevant fatigue)

Patient Health Questionnaire-9 :

8 points (mild depression)

Past Medical History

Non-insulin-dependent type 2 diabetes mellitus

Hypertension

Depressive disorder NOS

Seasonal allergies

Past Surgical History

Tonsillectomy in childhood

Cholecystectomy at age 43 years

Allergies

Pollen

Dust

Fluoroquinolone antibiotics

Medications

Family History

Type 2 diabetes mellitus, father

Coronary artery disease, mother

Obstructive sleep apnea, mother and brother

Ischemic stroke, maternal grandfather

Social History

She is married and has 2 children. Her youngest child is 19 years old and recently left home for college. The patient is a homemaker, and lives at home with her husband. She does not smoke cigarettes or drink alcohol. She does not use recreational drugs.

Review of Systems

All systems were reviewed, and all concerns are noted above in the patient’s history.

Vital Signs

Blood pressure:

123/76 mmHg

Heart rate:

72 beats per minute

Respiratory rate:

14 breaths per minute

Height:

5 feet 3 inches

Weight:

159 pounds

BMI:

28 kg/m²

Physical Examination

General:

Normal body habitus. No apparent distress.

Eyes:

No conjunctival erythema, no scleral icterus.

ENT:

Ears unremarkable, hearing intact, nasal airflow unrestricted, nasal septum deviated to right, inferior nasal turbinates unremarkable, tongue large with scalloping, hard and soft palate unremarkable, uvula long, tonsils not visible, Friedman Class 3 airway.

Neck:

12.5-inches neck circumference, no cervical lymphadenopathy.

Respiratory:

Clear to auscultation bilaterally, no wheezing/rhonchi/crackles.

Cardiovascular:

Regular rate and rhythm, no murmur, rubs or gallops. No carotid bruit.

Musculoskeletal:

Normal gait and station.

Extremities:

No cyanosis, clubbing, or edema.

Skin:

No rash, lesions ulcers, induration, or nodules in visible regions.

Neurologic:

Cranial nerves II–XII are intact.

Mental status:

Alert and fully oriented, judgment and insight are good, her mood is Down.

Differential Diagnosis

Obstructive sleep apnea

Depressive disorder NOS

Sleepiness due to use of diphenhydramine

Diagnostic Testing

Diagnostic Polysomnogram (PSG)

Total sleep time:

315 minutes

Latency to sleep:

53.5 minutes

REM latency:

67 minutes

Wake after sleep onset:

44.5 minutes

Sleep efficiency:

76.1%

Apnea-hypopnea index (AHI):

18.5 events per hour of sleep

REM AHI:

33.3 events per hour of sleep

AHI with 4% O2 desaturation:

2.5 events per hour

Obstructive apnea index:

0.0 events per hour

Central apnea index:

0.0 events per hour

Hypopnea index:

18.5 events per hour

Mean sleep % SpO2:

97%

Min sleep % SpO2:

87%

Periodic limb movement index:

5.5 limb movements per hour

Assessment

Symptoms of fatigue, sleepiness, loud snoring, snort arousals, and frequent nocturnal awakenings in this post-menopausal woman with a crowded oropharynx are consistent with her polysomnographic diagnosis of moderate obstructive sleep apnea (OSA) (Figs. 1.1 and 1.2). While mild depression and intermittent use of diphenhydramine as a sleep aid could contribute to sleep fragmentation and reduced daytime energy, these factors are unlikely to be the primary cause of the patient’s symptoms.

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Fig. 1.1

A 90-second epoch shows an obstructive hypopnea during rapid eye movement (REM) sleep

../images/467236_1_En_1_Chapter/467236_1_En_1_Fig2_HTML.png

Fig. 1.2

A hypnogram shows REM-predominant obstructive sleep apnea , exclusively in the form of obstructive hypopneas

Diagnosis

Obstructive sleep apnea

Treatment

The patient’s sleepiness and fatigue resolved after 1 month of consistent use of auto-titrating continuous positive airway pressure (CPAP) for an average of 6 hours per night. Her mood also improved with this treatment, and she was able to discontinue use of diphenhydramine at bedtime.

Discussion

Obstructive sleep apnea is caused by recurrent obstruction of the upper airway during sleep with resulting transient absence of airflow (apnea) or reduction of airflow (hypopnea) despite continued respiratory effort. Apneas and/or hypopneas cause transient hypoxemia, arousals from sleep, or both. A diagnosis of OSA requires five or more obstructive respiratory events per hour in a patient with symptoms of OSA (habitual snoring, witnessed apneas, etc.) or certain comorbidities (hypertension, coronary artery disease, etc.). Alternatively, OSA can be diagnosed if there are 15 or more obstructive respiratory events in the absence of symptoms or associated medical conditions [1].

The number of apneas and hypopneas per hour of sleep (with EEG) or recording time (without EEG) is called the apnea-hypopnea index (AHI) and is a measure of OSA severity (an AHI of 5–15 is mild, 15–30 is moderate, and greater than 30 is severe). The patient in the above case has an AHI of 18.5 (moderate OSA).

OSA is a relatively common condition with an estimated global prevalence of approximately 3–7% [2]. In the United States, the prevalence of OSA is approximately 15% in men and 5% in women [3]. Risk factors for OSA include increasing age, male gender, obesity, menopause, craniofacial anomalies (e.g., retrognathia), and a family history of OSA. Many studies have confirmed that menopause independently increases the risk of OSA after adjusting for confounding factors; one study showed that post-menopausal women have approximately threefold increased odds of moderate OSA (an AHI greater than or equal to 15 events per hour) compared to perimenopausal women [4, 5].

In addition to her increased risk for OSA as a post-menopausal woman, the patient in the above case reports loud snoring, gasp arousals, and excessive daytime sleepiness (EDS) , all of which are clinical features commonly encountered in patients with OSA. The Epworth Sleepiness Scale (ESS) , a validated measure of one’s average sleep propensity, is often used to quantify sleepiness in patients with and without OSA [6]. ESS scores greater than 10 are indicative of EDS. ESS scores have been shown to increase with the severity of OSA as measured by the respiratory disturbance index (RDI; the average number of obstructive apneas, hypopneas, and respiratory-event-related arousals per hour) [7]. However, one study did not find a statistically significant association between one’s ESS score and AHI, and a normal ESS does not rule out OSA [8].

Because EDS in patients with OSA can increase the risk of accidents/injuries and decrease quality of life, many studies have attempted to identify predictors of EDS in patients with OSA [9]. OSA severity as measured by the AHI or RDI does seem to correlate to increased sleepiness, but appears to be less important than sleep fragmentation (total arousals, arousal index, etc.) in provoking excessive sleepiness [10–12]. In addition, intermittent nocturnal hypoxemia without sleep fragmentation does not worsen daytime sleepiness in OSA patients treated with continuous positive airway pressure (CPAP) [13]. Other factors that may be predictive of EDS in OSA patients include severe snoring, increased sleep efficiency, and increased total sleep time [14, 15].

Although subjective sleepiness is often reported by patients with OSA, its absence does not rule out OSA; in certain populations of OSA patients, sleepiness may be reported less frequently than fatigue, tiredness, or low energy [16].

Treatment of OSA with CPAP has been shown to result in a greater reduction of subjective (ESS) and objective (multiple sleep latency test; MSLT ) measures of sleepiness relative to placebo [17]. Severe OSA (AHI ≥ 30), EDS, a high body movement index (number of body movements per hour of sleep), and high variability of EEG sleep depth have been shown to be predictive of a greater reduction in sleepiness following CPAP therapy [17, 18]. One study showed that increased alertness (as measured by a modified maintenance of wakefulness test) following CPAP therapy correlated strongly with a reduction in measures of sleep fragmentation [19]. Indeed, subjective (Stanford Sleepiness Scale ) and objective (MSLT) sleepiness may improve after only one night of CPAP use, and one subsequent night without CPAP can return sleepiness to its pre-treatment level [20].

A linear dose-response relationship (p < 0.01) has been shown between increasing CPAP use duration and decreasing subjective (ESS) and objective (MSLT) measures of sleepiness after 3 months of CPAP use in patients with a baseline AHI ≥ 15 [21]. Also, greater pre-treatment sleepiness (ESS > 10) in patients with OSA corresponds to higher rates of long-term (3+ years) CPAP use, possibly due to a greater perceived benefit from treatment [22].

While the sleepiness of the patient in the above case resolved after treatment with CPAP, some OSA patients struggle with persistent EDS despite CPAP use. In such cases, it is important to ensure complete treatment efficacy and excellent treatment adherence. If the patient struggles with EDS despite optimal CPAP efficacy and adherence, inadequate sleep hygiene and insufficient sleep should be corrected. When clinically indicated, other sleep disorders (e.g., narcolepsy) and medical conditions known to cause sleepiness should be investigated and treated if present (Fig. 1.7) [23].

For OSA patients with EDS despite effective and regular CPAP use in whom no other treatable causes of EDS are present, the wake-promoting medication modafinil may be prescribed and is approved by the Food and Drug Administration (FDA) of the United States of America (USA) for use in this patient population. The efficacy and tolerability of modafinil (for up to 12 weeks) in OSA patients with refractory EDS despite effective CPAP therapy has been shown in a number of randomized, double-blind, placebo-controlled trials [24, 25].

Key Learning Points

Patients with OSA often complain of EDS.

It is important to ask patients about decreased energy or fatigue; the absence of EDS does not rule out OSA.

Sleep fragmentation is one of the most important causes of sleepiness in patients with OSA.

Intermittent nocturnal hypoxemia is not a major contributor to EDS in patients with OSA.

Other factors that may predict EDS in OSA patients include severe snoring, increased sleep efficiency, and increased total sleep time.

Treatment of OSA with CPAP can reduce sleepiness, an effect that is due in part to reduced sleep fragmentation.

A longer duration of nightly CPAP use results in a greater reduction in daytime sleepiness.

Greater pre-treatment sleepiness in patients with OSA corresponds to higher rates of long-term CPAP use.

If a patient has EDS despite excellent CPAP efficacy and adherence, sleep hygiene and sleep duration should be optimized. When clinically indicated, other sleep disorders (e.g., narcolepsy) and medical conditions known to cause sleepiness should be investigated and treated if present.

The efficacy and tolerability of modafinil for OSA patients with refractory EDS despite effective CPAP treatment has been shown in a number of randomized, double-blind, placebo-controlled trials.

Case 2: Narcolepsy Type 1

History

A 23-year-old obese man presents to a sleep medicine clinic complaining of daytime sleepiness . Approximately 4 years ago, when he was a sophomore in college, the patient noticed daytime sleepiness that made it difficult for him to stay awake during lectures and complete assigned coursework. A brief afternoon nap would at times reduce his sleepiness, but the benefit was never sustained. The patient’s academic performance began to decline, so he sought help at the university’s Student Health Services (SHS) office. An SHS physician elicited a history of evening marijuana and alcohol use during weekend social outings with friends, often followed by brief low-quality nocturnal sleep. In addition to recommending cessation of alcohol and marijuana use, the physician ordered a polysomnogram (PSG) , which showed mild intermittent snoring without obstructive sleep apnea. A complete blood count and comprehensive metabolic panel also were normal.

Differential Diagnosis

Insufficient sleep

Circadian rhythm sleep-wake disorder

Sleep-disordered breathing

Central disorder of hypersomnolence (e.g., narcolepsy)

Mood disorder (e.g., atypical depression)

Sleepiness due to a medication/substance

Sleep-related movement disorder

History Continued

Despite discontinuing use of alcohol and marijuana, and ensuring that he slept for at least 7 hours per night, the patient remains sleepy during the day. A few times, he has fallen asleep quickly at work despite his best efforts to remain awake. During the past 4 months, he has also had three episodes of muscle weakness triggered by mirth and laughter. Twice the weakness only affected his face, and once his legs also became weak, causing him to slump to the ground. He remained conscious during these episodes, all of which gradually resolved within 1 minute.

Also, approximately once per month during the past year, he has awakened from sleep and been unable to move his body for 10–20 seconds prior to regaining normal motor function. He had experienced this in college as well, but it never occurred more than a few times per year. He denies hypnagogic or hypnopompic hallucinations.

His girlfriend told him that he snores loudly at times, but she has never witnessed apneas. He denies symptoms consistent with parasomnia, and denies symptoms of restless legs syndrome. Due in part to occupational and social distress resulting from the above symptoms, the patient endorses a depressed mood.

Sleep Schedule/Sleep Hygiene

The patient sleeps alone or with his girlfriend in a full-size bed. He uses his smart phone in bed and watches television in bed. He usually falls asleep on his back, and his girlfriend tells him that he tosses and turns at night, frequently changing his body position.

Time in bed:

10:00 PM

Lights out:

10:15 PM

Sleep onset latency:

5 minutes or less

Sleep aids:

None

Number of awakenings:

0–1

Cause of awakenings:

Unknown

Wake after sleep onset time:

10–15 minutes

Wake time:

6:00 AM

Rise time:

6:15 AM

Naps:

Daily, usually from 12:00 to 12:30 PM. Naps are refreshing.

Total sleep time:

Approximately 8 hours per 24-hour period

Scales/Questionnaires

STOP-BANG Scale :

2 points (low risk of obstructive sleep apnea)

Epworth Sleepiness Scale :

19 points (excessive daytime sleepiness)

Patient Health Questionnaire-9 :

11 points (moderate depression)

Past Medical History

Asthma

Obesity

Depressive disorder NOS

Past Surgical History

Adenotonsillectomy at age 4 years

Appendectomy at age 9 years

Allergies

Nuts

Shellfish

Penicillin

Medications

Family History

Celiac disease, mother

Depression, father

Hypertension, paternal grandfather

Rheumatoid arthritis, sister and maternal grandmother

Social History

He is unmarried and in a stable relationship with his girlfriend. After completing a bachelor’s degree in accounting and passing his Certified Public Accountant (CPA) examination, he started working at a local accounting firm. He lives alone in an apartment. The patient does not smoke cigarettes and rarely drinks small amounts of alcohol with friends. He does not use recreational drugs.

Review of Systems

All systems were reviewed, and all concerns are noted above in the patient’s history.

Vital Signs

Blood pressure:

112/70 mmHg

Heart rate:

64 beats per minute

Respiratory rate:

12 breaths per minute

Height:

6 feet 2 inches

Weight:

268 pounds

BMI:

34 kg/m²

Physical Examination

General:

Obese body habitus. No apparent distress.

Eyes:

No conjunctival erythema, no scleral icterus.

ENT:

Ears unremarkable, hearing intact, nasal airflow unrestricted, nasal septum midline, inferior nasal turbinates unremarkable, tongue large without scalloping, hard and soft palate unremarkable, uvula normal, tonsils not visible, Friedman Class 2–3 airway.

Neck:

15.5-inches neck circumference, no cervical lymphadenopathy.

Respiratory:

Clear to auscultation bilaterally, no wheezing/rhonchi/crackles.

Cardiovascular:

Regular rate and rhythm, no murmur, rubs or gallops. No carotid bruit.

Musculoskeletal:

Normal gait and station.

Extremities:

No cyanosis, clubbing, or edema.

Skin:

No rash, lesions ulcers, induration, or nodules in visible regions.

Neurologic:

Cranial nerves II–XII are intact.

Mental status:

Alert and fully oriented, judgment and insight are good, and he describes his mood as Not very good.

Differential Diagnosis

Narcolepsy type 1

Depressive disorder NOS

Sleep-disordered breathing

Diagnostic Testing

Actigraphy and Sleep Diary (2 Weeks)

Regular bedtimes (10:00 PM) and get-up times (6:00–6:30 AM) without circadian rhythm abnormality, and with an average estimated total sleep time of 8 hours per 24-hour period.

Average sleep onset latency of 5 minutes and sleep efficiency of 86%.

Actigraphy supported the content of the sleep diary without significant discrepancies.

Diagnostic Polysomnogram (PSG) with End-Tidal CO2 Monitoring

Total sleep time:

481 minutes

Latency to sleep:

12 minutes

Rapid-eye-movement (REM) latency:

100 minutes

Wake after sleep onset:

21 minutes

Sleep efficiency:

93.4%

Apnea-hypopnea index (AHI):

2.2 events per hour of sleep

REM AHI:

0.4 events per hour of sleep

AHI with 4% O2 desaturation:

2.5 events per hour

Obstructive apnea index:

0.1 events per hour

Central apnea index:

0.5 events per hour

Hypopnea index:

1.6 events per hour

Mean sleep % SpO2:

96%

Min sleep % SpO2:

85%

End-tidal CO2:

No evidence of sleep-related hypoventilation

Periodic limb movement index:

0.0 limb movements per hour

Urine toxicology screen (the morning preceding the multiple sleep latency test): Negative

Multiple Sleep Latency Test (MSLT)

../images/467236_1_En_1_Chapter/467236_1_En_1_Fig3_HTML.png

Fig. 1.3

A hypnogram shows the absence of sleep-disordered breathing, normal sleep architecture, and a short sleep onset latency

Table 1.1

A chart of five naps shows a mean sleep onset latency of 3 minutes and three sleep-onset REM periods (SOREMPs), occurring in the last three naps

../images/467236_1_En_1_Chapter/467236_1_En_1_Fig4_HTML.png

Fig. 1.4

A hypnogram from the multiple sleep latency test (MSLT) shows sleep during all five naps and SOREMPs during the final three naps

Assessment

Symptoms of excessive daytime sleepiness, sleep attacks, cataplexy, and recurrent sleep paralysis in this obese young man are strongly suggestive of narcolepsy type 1. This diagnosis was confirmed by studies that showed adequate total sleep time, a normal circadian rhythm, the absence of sleep-disordered breathing (Fig. 1.3), and three sleep-onset REM periods (SOREMPs) on MSLT with a mean sleep latency of 3 minutes (Table 1.1 and Fig. 1.4).

Diagnosis

Narcolepsy type 1

Treatment

Modafinil was prescribed and significantly reduced the patient’s daytime sleepiness at a dose of 200 MG in the morning. Extended-release venlafaxine also was prescribed for cataplexy and has resulted in resolution of cataplexy at a dose of 75 MG per day; this medication also reduced the severity of the patient’s depressed mood. He established care with a psychotherapist, who he sees every 6 months, and he joined an exercise group that meets three times per week at a local gymnasium. The patient occasionally takes a brief mid-day nap at work and his productivity has increased since he started the treatments above. He continues to sleep at least 7 hours each night and he never drinks alcohol.

Discussion

Narcolepsy results from impairment of the orexin (also known as hypocretin ) signaling pathway in the brain. Orexin is a wake-promoting neuropeptide made by neurons in the lateral hypothalamus. Patients with narcolepsy type 1 (narcolepsy with cataplexy) have up to 90% less orexin-producing hypothalamic neurons [26]. As a result, these patients have absent or severely deficient (≤110 pg/mL) orexin in their cerebrospinal fluid (CSF) [27]. Due to practical limitations, however, CSF analysis is not routinely performed in the evaluation of patients with suspected narcolepsy. The cause of narcolepsy type 2 (narcolepsy without cataplexy) is unknown, and the majority of these patients have normal CSF orexin levels; it is possible that these patients have abnormal orexin receptors, leading to functional impairment of orexin signaling despite normal orexin levels. Structural damage to orexin-producing neurons and/or pathways can cause secondary narcolepsy, which may be due to neurosarcoidosis, ischemic or hemorrhagic stroke, or neoplasm, for example.

The patient in the above case has narcolepsy type 1. In order to diagnose narcolepsy type 1, a patient must have the following:

Daily periods of irrepressible need to sleep or daytime lapses into sleep occurring for at least 3 months

One or both of the following:

Cataplexy and a mean sleep latency of ≤8 minutes and two or more SOREMPs on an MSLT performed according to standard techniques. A SOREMP (within 15 minutes of sleep onset) on the preceding nocturnal PSG may replace one of the SOREMPs on the MSLT.

CSF hypocretin-1 concentration, measured by immunoreactivity, is either ≤110 pg/mL or less than one-third of mean values obtained in normal subjects with the same standardized assay [28].

Therefore, the above patient meets diagnostic criteria for narcolepsy type 1 based upon a daily irrepressible need to sleep for more than 3 months, cataplexy, a mean sleep latency of 3 minutes, and three SOREMPs on an MSLT. In addition, there is not an alternative explanation for the patient’s sleepiness (e.g., sleep-disordered breathing), and the SOREMPs are not better explained by sleep deprivation or circadian disruption.

Narcolepsy type 1 is uncommon, with an estimated prevalence of up to 1 in 2000 people based primarily on populations of men and women in the United States of America (USA) and Europe [29]. As seen in the above case, symptom onset usually occurs in one’s late teens or early twenties, though initial symptoms at younger and older ages have also been reported.

The DQB1*0602 haplotype is found in up to 95% of narcolepsy patients with cataplexy, prompting some scientists to propose that narcolepsy may be triggered by an autoimmune process [30]. It is important to note, however, that the DQB1*0602 haplotype also may be found in 12–30% of the general population, and its presence is therefore not confirmatory of narcolepsy, only supportive of this diagnosis in the right clinical context [31]. Further support for the autoimmune hypothesis derives from studies showing narcolepsy type 1 onset in European patients after administration of the AS03-adjuvanted 2009 H1N1 influenza vaccine, and an April peak of narcolepsy onset in Chinese patients possibly due to winter infection [32, 33]. While the majority of cases of narcolepsy type 1 are sporadic, familial narcolepsy has been reported and the precise genetic mechanisms are unknown.

Narcolepsy is fundamentally a disorder of sleep-wake regulation with sleepiness during wakefulness, REM sleep intrusion into wakefulness, prominent sleep fragmentation, and rapid sleep onset. The primary, universal clinical feature of narcolepsy is excessive daytime sleepiness (EDS) , which may occur in isolation. Patients with narcolepsy usually have an Epworth Sleepiness Scale score greater than 15, which is significantly higher than that of patients with EDS due to other sleep disorders such as obstructive sleep apnea (OSA) [34]. The