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Running head: NARCOLEPSY CASE STUDY
Narcolepsy Case Study Review
Faith Sola
Liberty University
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NARCOLEPSY CASE STUDY
Narcolepsy Case Study Review
Narcolepsy is a neurological disorder affecting the brain’s ability to manipulate sleep-
wake cycles effectively, resulting in daily activities and normal sleep patterns. The affected
following case study by Fortuyn et al. (2010) investigated the plausible association between
anxiety and mood disorders in narcoleptic patients.
Case Study
Abundant research has been focused on the pathophysiology of narcolepsy, a sleep
disorder characterized by excessive daytime sleepiness (EDS), cataplexy (sudden bilateral loss of
muscle tone; partial or complete paralysis of muscles), hypnagogic hallucinations, and sleep
paralysis (Akintomide & Rickards, 2011; Fortuyn et al., 2010; “Narcolepsy fact sheet,” 2019;
Scammell, 2015; Vanderah & Gould, 2015). Additionally, psychiatric symptoms and disorders
such as eating disorders and psychotic symptoms have occasionally been reported in narcolepsy
patients. However, anxiety and mood disorders are not commonly associated together with
narcolepsy.
In this study, the researchers investigated the association between narcolepsy and
anxiety/mood disorders in 60 narcolepsy patients and 120 age-, sex-, and environment-matched
control individuals from the Netherlands. About two-thirds of the narcolepsy patients recruited
were used stimulant medication, antidepressants, or sodium oxybate to control their EDS or
cataplexy. All narcolepsy participants were recruited from an outpatient clinic specialized in
sleep medicine, and all participants were diagnosed with narcolepsy with cataplexy based on the
International Classification of Sleep Disorders (ICSD-2) for Narcolepsy standards before
participation in the study. Controls participants were recruited from a nearby university medical
center.
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The researchers used Schedules for Clinical Assessment in Neuropsychiatry (SCAN) as a
reliable and valid diagnostic classification instrument for assessing symptoms of anxiety and
mood disorders. The presence and quality of symptoms including worrying, tension, panic,
anxiety, phobias, obsessional symptoms, depression, thinking, concentration, and energy were
assessed and rated through a structured interview, respectively. The researchers’ results were
conclusive and many anxiety- and mood-like symptoms were acknowledged by narcolepsy
participants. Worrying and tension symptoms were present significantly more in narcolepsy
participants than controls; similarly, panic, anxiety, and phobic symptoms (ex., panic attacks and
social phobias) were present significantly in over half of all narcolepsy patients especially during
hypnagogic hallucinations. Additionally, depression, loss of concentration, and loss of energy
were significantly correlated with narcolepsy patients compared to controls but were also the
most striking interference with daily activities mentions by over 90% of narcolepsy patients.
The study portrays that anxiety-like symptoms, more than depression-like symptoms,
dominate the psychiatric domain of narcolepsy patients compared to controls. The frequent
occurrence of anxiety-like symptoms in narcolepsy patients fosters notable explanations. For
example, anxiety and mood symptoms in narcolepsy patients may be a direct outcome of the
neuropathophysiology of the disease. On the other hand, anxiety may be a secondary
consequence to having narcolepsy and being chronically exposed to anxiety-inducing
experiences (i.e., hypnagogic hallucinations, crowds, collapsing alone or without help).
Nonetheless, narcolepsy can have debilitating effects on the patient’s own life and the
lives of those around them. For example, there is an increased risk of motor vehicle accidents
among people with narcolepsy (Scammell, 2015). Also, narcolepsy patients may have to reject
their emotions, whether positive or negative, to prevent a cataplexy flare-up. This may lead to
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severed interpersonal relationships, anxiety and mood disorder-like symptoms, and social
isolation (Fortuyn et al., 2010).
Narcolepsy
Narcolepsy and the Sleep Cycle
In a normal sleep cycle, individuals enter rapid eye movement (REM) sleep within 60 to
90 minutes during which dreaming occurs and skeletal muscles are limp. On the other hand,
REM sleep can occur at any time of the day in narcoleptic individuals with many entering REM
sleep within 15 minutes. As a result, many REM elements intrude into wakefulness, creating a
distorted intermediate state, the source of hypnagogic hallucinations.
Epidemiology
Narcolepsy affects approximately 1 in every 2,000 individuals, and its incidence rate is
highest in males in the second decade. However, symptoms can start manifesting in childhood
(Akintomide & Rickards, 2011; “Narcolepsy fact sheet,” 2019; Scammell, 2015).
Classification and Diagnosis
According to the ICSD-2 (2005), there are three types of narcolepsy: narcolepsy with
cataplexy (type 1), narcolepsy without cataplexy (type 2), and secondary narcolepsy
(Akintomide & Rickards, 2011; “Narcolepsy fact sheet,” 2019; Scammell, 2015). Type 1
narcolepsy is measured diagnostically based on reported cataplexy or low hypocretin levels
(discussed in the following section). For type 2 narcolepsy, patients do not have a loss of muscle
tone and/or weakness seen in cataplexy and usually have temperate symptoms and normal
hypocretin levels. Secondary narcolepsy is expressed in patients as narcolepsy-like symptoms,
but the condition is associated with an irrelative medical condition.
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Moreover, primary and secondary etiologies of narcolepsy include autoimmune disorders
causing hypocretin deficiency, family history, and brain injuries. Brain injuries such as
hypothalamic adhesions, brain tumors, demyelinating diseases, encephalomyelitis, craniocerebral
trauma, and neurodegenerative diseases are most commonly attributed with narcolepsy
development (Akintomide & Rickards, 2011). Differential diagnoses include medical conditions
commonly associated with sleepiness (e.g., respiratory and cardiac disorders), major psychiatric
disorder sharing symptoms of functional impairments, insomnia, and hypersomnia, neurological
conditions commonly associated with sleepiness and REM sleep behavioral disorders (e.g.,
Parkinson’s Disease and Alzheimer’s Disease), and malingering (Akintomide & Rickards, 2011).
Furthermore, the prognosis of narcolepsy can be uneventful. Narcolepsy is a life-long
disease, but with proper management and treatment, patients with narcolepsy can lead
meaningful and productive personal and professional lives. If left untreated, narcolepsy may be
psychosocially devastating; narcoleptic patients may suffer poor academic and professional
performance, social impairment, and anxiety (Scammell, 2015).
Pathophysiology
Hypocretins. Recent research investigating the effects of hypocretin neurotransmission
deficiency has sparked a new interest in narcoleptic pathophysiology. Hypocretins 1 and 2, or
orexins A and B, are two hypothalamic neuropeptides that function in regulating wakefulness
(Akintomide & Rickards, 2011; Ebrahim, Howard, Kopelman, Sharief, & Williams, 2002;
Fortuyn et al., 2010; “Narcolepsy fact sheet,” 2019; “The science of narcolepsy,” 2018;
Scammell, 2015). Hypocretin neurons are active during wakefulness and stimulate many
wakefulness-promoting neurons in the cortex, brain stem, hypothalamus, and basal forebrain that
in turn produce neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine.
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Hypocretins also suppress REM sleep (Scammell, 2015). In type 1 narcolepsy, there is a loss of
hypocretin-producing neurons, prompting inconsistent firings and reduced neurotransmitter
release. As a result, an increased triggering sleepiness, lapses in sleep, and poor regulation of
REM sleep become apparent (Figure 1a). In cataplexy, strong emotions activate the amygdala
and medial prefrontal cortex. Due to the hypocretin loss demonstrated in narcolepsy type 1, there
is reduced activity in the brain regions that inhibit REM sleep, activating descending pathways
that will inhibit lower motor neurons, resulting in cataplexy (Figure 1b).
Furthermore, animal research has demonstrated that hypocretin defects lead to abnormal
reward processing similar to those suffering with social anxiety disorder (Fortuyn et al., 2010).
Therefore, a direct connection between anxiety and mood disorders and hypocretin deficiency is
a plausible explanation for the anxiety-like symptoms seen in the narcolepsy patients of the case
study (Fortuyn et al., 2010).
Genetics: HLA haplotype. More than 85% of patients with narcolepsy with cataplexy
have an inherited gene that codes for human leukocyte antigen (HLA DQB1*0602), which is
important for immune function (Akintomide & Rickards, 2011; “The science of narcolepsy,”
2018). Recent evidence proclaim that immune processes can kill hypocretin neurons suggesting
a possible proclamation that narcolepsy is an autoimmune disease in which the immune system
destroys hypocretin-secreting cells (“The science of narcolepsy,” 2018).
Treatment
Narcolepsy cannot be cured or prevented. However, in most cases, narcolepsy-like
symptoms can be diminished with medication and regularly scheduled naps. In fact, medication
and lifestyle changes are the two primary modes of treatment for narcolepsy patients.
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Medications such as antidepressants, Modafinil, amphetamine-like stimulants, and
sodium oxyborate are the most common (Akintomide & Rickards, 2011; “Narcolepsy fact
sheet,” 2019; Scammell, 2015; Wise et al., 2007). Wise et al. (2007), investigated known
treatment options of narcolepsy and other hypersomnias. Their results concluded that traditional
stimulants such as amphetamine, dextroamphetamine, methamphetamine, and methylphenidate
are considered mainstays for treatment of EDS in narcolepsy patients. Additionally, sodium
oxybate is a commonly prescribed sedative/hypnotic medication that can treat narcolepsy-like
symptoms, cataplexy, and disrupted nocturnal sleep. Modafinil, is an altering agent that has been
extensively researched in sleep disorder medical archives (Wise et al., 2007). However,
modafinil has many adverse effects including headaches, anxiety, nausea, dry mouth, dizziness,
insomnia, and asthenia. Therefore, modafinil is not regularly prescribed for narcolepsy; and if it
is, only in small doses or with other medications. Other treatments like selegiline, reboxetine,
pemoline, and ritanserin are useful when treating sleepiness and cataplexy.
Lifestyle improvements including exercise, maintaining a short sleep schedule, and
avoiding smoking and caffeine ingestion at night are the most helpful strategies for patients with
narcolepsy. Patients should be consistent with their lifestyle improvements to witness the most
optimal effects.
Questions and Future Research
Pathophysiology. It remains unclear exactly why hypocretin neurons die; additional
research in this field is needed to understand the underlying mechanisms of hypocretin
neurogenesis.
Treatments. Future investigations should be directed toward development of more
effective and better tolerated therapies for children, pregnant and breastfeeding women, and the
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elderly. Also, primary prevention of narcolepsy is imperative in addition to therapies that are
symptomatic in nature (Wise et al., 2007). Finally, anxiety symptoms are not regularly reported
in narcolepsy patients; therefore, physicians should be observant for any cues that can indicate
anxiety- or mood-like symptoms (Fortuyn et al., 2010).
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References
Akintomide, G. S., & Rickards, H. (2011). Narcolepsy: A review. Neuropsychiatric Disease and
Treatment 7, (1), 507–518. https://doi.org/10.2147/ndt.s23624
Ebrahim, I. O., Howard, R. S., Kopelman, M. D., Sharief, M. K., & Williams, A. J. (2002). The
hypocretin/orexin system. Journal of the Royal Society of Medicine, 95(5), 227–230.
https://doi.org/10.1258/jrsm.95.5.227
Fortuyn, H. A. D., Lappenschaar, M. A., Furer, J. W., Hodiamont, P. P., Rijnders, C. A. T., Renier, W.
O., … Overeem, S. (2010). Anxiety and mood disorders in narcolepsy: A case-control study.
General Hospital Psychiatry, 32(1), 49–56. https://doi.org/10.1016/j.genhosppsych.2009.08.007
National Institute of neurological Disorders and Stroke. (2019). Narcolepsy fact sheet. Retrieved
from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-
Sheets/Narcolepsy-Fact-Sheet
Scammell, T. E. (2015). Narcolepsy. New England Journal of Medicine, 373(27), 2654–2662.
https://doi.org/10.1056/NEJMra1500587
Harvard Medical School. (2018). The science of narcolepsy. Retrieved from
http://healthysleep.med.harvard.edu/narcolepsy/what-is-narcolepsy/science-of-narcolepsy
Vanderah, T., & Gould, D. (2015). Cerebral Cortex. In Nolte’s the human brain: An introduction to
its functional anatomy (p. 575).
Wise, M. S., Arand, D. L., Auger, R. R., Brooks, S. N., Watson, N. F., & American Academy of Sleep
Medicine. (2007). Treatment of narcolepsy and other hypersomnias of central origin. , Sleep
30(12), 1712–1727. Retrieved from
http://www.ncbi.nlm.nih.gov/pubmed/18246981%0Ahttp://www.pubmedcentral.nih.gov/articler
ender.fcgi?artid=PMC2276130
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Appendix
Figure 1. Neurobiologic mechanisms of narcolepsy. Reprinted from
Scammell, T. E. (2015). Narcolepsy. , (27), 2654–New England Journal of Medicine 373
2662. https://doi.org/10.1056/NEJMra1500587
