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Narcolepsy

Narcolepsy-Cataplexy

Narcolepsy is a chronic neurological disorder characterized by the classic tetrad of excessive daytime sleepiness, cataplexy, sleep paralysis and hypnagogic hallucinations. The first descriptions of narcolepsy-cataplexy were reported in Germany by Westphal and Fisher in 1877/1878.


Presentation

The classic tetrad of narcolepsy consists of excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. In very few cases it is seen that a child presents with all 4 symptoms [13].

EDS is the primary symptom of narcolepsy and must be present for at least 3 months to justify the diagnosis. In persons with narcolepsy, severe EDS leads to involuntary somnolence during activities that normally need attention, like driving, eating, or talking. Narcoleptic patient can suffer from severe and constant sleepiness, with bouts of falling asleep without any warning (i.e. sleep attacks).

Patients with narcolepsy tend to take short and refreshing naps (i.e. rapid eye movement (REM)-type naps) during the day. Sometimes dreams also accompany the daytime naps.

A significant number of narcolepsy patients have trouble sleeping at night [14]. In addition, patients may have nocturnal compulsive habits like, eating disorder in relation with sleep and smoking at night [15]. Obesity is commonly seen with narcolepsy.

Cataplexy is a brief and sudden loss of muscle tone and represents REM sleep intrusion during wakefulness. The most characteristic feature of cataplexy is that it usually is triggered by emotions (especially laughter and anger). Cataplexy is seen in about 70% of patients with narcolepsy. The presence of cataplexy along with EDS is strongly suggestive of narcolepsy.

Patients with narcolepsy may experience sleep paralysis, in which the patient is not able to move when he/she wakes up and sometimes when asleep with consciousness intact. Often hallucinations accompany it. Sleep paralysis occurs less frequently when patients sleep in uncomfortable positions. The person can be rescued from this condition by sensory stimuli, like touch or talking with that person.

Sleep-related hallucinations may be either hypnagogic (i.e. occurring at sleep onset) or hypnopompic (i.e. occurring at awakening). These hallucinations are usually vivid (dreamy) either tactile, visual or auditory in character.

At disease onset, children with narcolepsy and cataplexy may display a wide range of motor disturbances that do not corroborate with cataplexy as it is classically. The motor disturbances, can be negative (hypotonia) or active (e.g. perioral movements, dyskinetic-dystonic movements, or stereotypic movements), and are seen to settle later during the course of disease [16].

In children aged 5-10 years, inattentiveness is the most common initial complaint, followed by recurring sleepiness and later on by difficulty in morning arousal associated with aggressive behavior and abrupt falls in school [17]. These children often were misdiagnosed as having attention deficit hyperactivity disorder (ADHD), learning disability, depression, or another neurological disorder. In children aged 10-12 years, poor academic performance is a common complaint [17].

Physically, narcoleptic patients are normal.

Excessive Daytime Sleepiness
  • Sodium oxybate has many unique properties that cause it to differ from past therapies for cataplexy and excessive daytime sleepiness associated with narcolepsy.[ncbi.nlm.nih.gov]
  • Narcolepsy is a rare but disabling condition that causes excessive daytime sleepiness. Interestingly, weight gain is frequent in patients with narcolepsy and it has sometimes been described very early in the course of the disease.[ncbi.nlm.nih.gov]
  • Abstract Narcolepsy represents the best understood disorder of excessive daytime sleepiness (EDS).[ncbi.nlm.nih.gov]
  • RESULTS: Of the seven scales reviewed, the Epworth Sleepiness Scale continues to be an important outcome measure to screen adults for excessive daytime sleepiness, which may be associated with narcolepsy.[ncbi.nlm.nih.gov]
  • Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM) sleep abnormalities.[ncbi.nlm.nih.gov]
Falling
  • They may fall asleep while talking or eating, or during sporting events and social activities.[nhlbi.nih.gov]
  • During the attack, your head falls forward, your jaw drops, and your knees may buckle. In severe cases, you may fall and stay paralyzed for as long as several minutes.[nlm.nih.gov]
  • This test detects the tendency to fall asleep quickly, REM movement soon after falling asleep, and waking up often during the night. Multiple sleep latency test This test is usually done during the day after an overnight PSG.[web.archive.org]
  • The boy presented with a history of increased suddenly falling frequency and excessive daytime sleepiness for 3 months. CMT1 was diagnosed by electrophysiology and genetic testing.[ncbi.nlm.nih.gov]
  • He falls, and his drowsiness ceases after the attack; he falls and the ictus never causes him to fall stiff, with resultant injuries of the type so common among epileptics. He falls and immediately recovers his wits, his intelligence. Ah![ncbi.nlm.nih.gov]
Hypersomnia
  • Between October 1st 2009 and December 31st 2012, 72 persons had onset of narcolepsy and 305 were diagnosed with hypersomnia.[ncbi.nlm.nih.gov]
  • The highest SWA was observed in the hypersomnia group, while the lowest in the narcolepsy group.[ncbi.nlm.nih.gov]
  • There were 274 patients with narcolepsy; hypersomnia; obstructive sleep apnea; restless legs syndrome; insomnia; and atypical hypersomnia cases such as familial cases, narcolepsy without cataplexy or without HLA-DQB1*0602, recurrent hypersomnias, and[ncbi.nlm.nih.gov]
  • KEYWORDS: Cataplexy; Idiopathic hypersomnia; Kleine Levin syndrome; Narcolepsy; Pharmacotherapy[ncbi.nlm.nih.gov]
  • Conversely, other central hypersomnias are less well-defined disorders with variability in the phenotype, and few reliable biomarkers have been discovered so far.[ncbi.nlm.nih.gov]
Fatigue
  • Overall, participants reported that fatigue and cognitive difficulties were their most burdensome symptoms in addition to sleepiness and cataplexy. The majority of participants reported residual daytime fatigue and/or sleepiness despite treatment.[ncbi.nlm.nih.gov]
  • The persons who suffer from this condition experience fatigue and may fall asleep at inappropriate times during the day.[icd9data.com]
  • Health care providers should include narcolepsy in the differential diagnosis of patients with excessive sleepiness, chronic fatigue, sleep-disordered breathing, depression, and attention-deficit/hyperactivity disorder.[ncbi.nlm.nih.gov]
  • Improving the quality of nighttime sleep can combat EDS and help relieve persistent feelings of fatigue.[web.archive.org]
Epilepsy
  • Narcolepsy type 1 and focal epilepsy was diagnosed. Some clinical symptoms of narcolepsy (cataplexy, automatic behavior, episodes of sleep attacks) need to be carefully analyzed by EEG and video-EEG not to overlook the epilepsy.[ncbi.nlm.nih.gov]
  • Four patients with comorbidity for narcolepsy type 1 and idiopathic generalized epilepsy are reported: in three cases the onset of epilepsy preceded narcolepsy type 1 appearance, whereas in one case epileptic spells onset was subsequent.[ncbi.nlm.nih.gov]
  • Video EEG testing finally confirmed the diagnosis of epilepsy; therefore, valproate was given and seizures were controlled completely.[ncbi.nlm.nih.gov]
  • This paper sets out to demonstrate the coexistence of juvenile myoclonic epilepsy (JME) and narcolepsy that raises the possibility of a shared genetic predisposition to both conditions.[ncbi.nlm.nih.gov]
  • Case 1 was a 15-year-old girl presenting with recurrent episodes of "convulsions" and loss of consciousness, who was referred to our hospital with a diagnosis of epilepsy showing "convulsions" and "complex partial seizures".[ncbi.nlm.nih.gov]
Sleep Apnea
  • SUBJECTS AND METHODS: Children between 6 and 17 years of age with narcolepsy that underwent adenotonsillectomy for non-severe obstructive sleep apnea (OSA) were included.[ncbi.nlm.nih.gov]
  • Other causes of daytime sleepiness, such as sleep apnea or periodic leg movements, are also excluded by the nocturnal recordings.[med.stanford.edu]
  • Severe periodic limb movements in sleep, severe sleep apnea, REM sleep behavior disorder and restless legs syndrome, which are frequently comorbid in NC and PD, were revealed.[ncbi.nlm.nih.gov]
  • She was diagnosed with obstructive sleep apnea (OSA) and underwent tonsillectomy and adenoidectomy. After the surgery, her sleep became much calmer, but she was still sleepy.[ncbi.nlm.nih.gov]
Diplopia
  • Occasionally there will be introductions of blurred vision or diplopia due to their sleepiness. Narcoleptics do not sleep longer than normal during a typical 24-hour period, but their sleep is non-restorative.[healthcentral.com]
  • Slurred speech and visual symptoms such as blurred vision or diplopia may be experienced. Hearing, awareness and consciousness are intact.[patient.info]
  • […] have HLA-DR2 and/or HLA-DQw1 Clinical Narcolepsy tetrad; if accompanied by cataplexy, Pt feels a sense of absolute urgency for sleep in often inappropriate situations–while standing, eating, carrying on conversations, accompanied by blurred vision, diplopia[medical-dictionary.thefreedictionary.com]
Muscle Hypotonia
  • Cataplectic attacks are evoked by a funny TV story and affect predominantly face muscles.[doi.org]
Aggressive Behavior
  • Children and adolescents with narcolepsy may struggle with emotional regulation and display aggressive behaviors that lead to social exclusion and feelings of self-loathing and shame.[wakeupnarcolepsy.org]
  • In children aged 5-10 years, inattentiveness is the most common initial complaint, followed by recurring sleepiness and later on by difficulty in morning arousal associated with aggressive behavior and abrupt falls in school.[symptoma.com]
  • While stimulants may be effective, potential side effects include dependence, aggressive behavior, and heart problems. Non-stimulant medications include modafinil and armodafinil.[web.archive.org]
Auditory Hallucination
  • Later, due to auditory hallucinations she was referred to a psychiatric hospital. Her reality judgement was poor, with partial insight regarding her illness.[ncbi.nlm.nih.gov]
  • These patients had auditory hallucinations, which was the most differentiating clinical feature in comparison to narcolepsy patients without psychosis.[ncbi.nlm.nih.gov]
  • hallucinations at the onset of sleep.[medical-dictionary.thefreedictionary.com]
Emotional Lability
  • Paradoxically, preschool and young children may show inattentiveness, emotional lability, and hyperactive behavior. Cataplexy may develop after onset of sleepiness and affect mainly muscles of the face.[ncbi.nlm.nih.gov]
Manic Behavior
  • Abstract We report the case of a 22-year-old male who exhibited severe manic behavior shortly after beginning treatment with modafinil and venlafaxine for narcolepsy with cataplexy.[ncbi.nlm.nih.gov]
Sleep Attack
  • Narcolepsy was suspected due to the attack induced by hearty laughs and the presence of sleep attacks, and confirmed by low orexin levels in cerebrospinal fluid (CSF).[ncbi.nlm.nih.gov]
  • Considered outcomes were: cataplexy attacks, subjective daytime sleepiness, sleep attacks, clinical global impression change (CGI-c), quality of life (QoL), hypnagogic hallucinations, sleep paralysis, mean sleep latencies on the multiple sleep latency[ncbi.nlm.nih.gov]
  • The following may help to avoid harm during sleep attacks: Avoiding being alone when one is likely to have a sleep attack. Taking a nap before times of the day when an attack is likely. Safeguarding the home and workspace.[web.archive.org]
  • Another possibility is that this man indeed had coitus with his wife while awake that was immediately followed by a sleep attack, and in retrospect he incorrectly recalled the coitus to have occurred during the sleep attack.[ncbi.nlm.nih.gov]
  • Two of the leading symptoms actually serve to reflect this phrase; they are the excessive sleepiness that is marked by “sleeping attacks” during the day that could be a physical version of a panic attack.[web.archive.org]
Automatic Behavior
  • Some clinical symptoms of narcolepsy (cataplexy, automatic behavior, episodes of sleep attacks) need to be carefully analyzed by EEG and video-EEG not to overlook the epilepsy.[ncbi.nlm.nih.gov]
  • Automatic behavior is a relatively newly recognized symptom of the narcolepsy syndrome. This case report describes a particularly troublesome sort of automatic behavior--shoplifting--in a narcoleptic patient.[ncbi.nlm.nih.gov]
  • A condition characterized by recurrent episodes of daytime somnolence and lapses in consciousness (microsomnias) that may be associated with automatic behaviors and amnesia.[icd9data.com]
  • This is called automatic behavior. During automatic behavior, you're not aware of your actions, so you don't do them well. For example, if you're writing before falling asleep, you may scribble rather than form words.[nhlbi.nih.gov]
  • Automatic behavior Automatic behavior is the performance of routine tasks by a person who is not consciously controlling the activity. Sometimes a person may actually fall asleep and continue an activity, but not recall having done it when awakened.[chop.edu]
Hyperactivity
  • Since cholinergic hyperactivity is a feature of narcolepsy-cataplexy, we transferred IgG from nine patients with narcolepsy and nine healthy controls to mice and assessed the effect on smooth muscle contractile responses to cholinergic stimulation.[ncbi.nlm.nih.gov]
  • Paradoxically, preschool and young children may show inattentiveness, emotional lability, and hyperactive behavior. Cataplexy may develop after onset of sleepiness and affect mainly muscles of the face.[ncbi.nlm.nih.gov]
  • Health care providers should include narcolepsy in the differential diagnosis of patients with excessive sleepiness, chronic fatigue, sleep-disordered breathing, depression, and attention-deficit/hyperactivity disorder.[ncbi.nlm.nih.gov]
  • The patient showed poor recognition performance off modafinil (z  -2.03) but intact performance on modafinil (z 0.78). fMRI results showed atypical activation during memory encoding off modafinil, with frontal lobe hypoactivity, but hippocampal hyperactivity[ncbi.nlm.nih.gov]
  • Also, they may seem hyperactive. Some children who have narcolepsy speed up their activities rather than slow them down. Children who have narcolepsy may have severe sleepiness.[nhlbi.nih.gov]
Somnolence
  • The patient's somnolence worsened, apparently accentuated by pramipexole treatment, as changing therapy to levodopa led to a reduction of sleepiness.[ncbi.nlm.nih.gov]
  • A condition characterized by recurrent episodes of daytime somnolence and lapses in consciousness (microsomnias) that may be associated with automatic behaviors and amnesia.[icd9data.com]
  • Narcolepsy is characterized by excessive daytime somnolence associated with sleep paralysis, hallucinations when falling asleep or awakening, and cataplexy. Early recognition of pediatric narcolepsy is essential for growth and development.[ncbi.nlm.nih.gov]
  • She currently has severe somnolence, obesity, and partial cataplectic attacks along with normal mood, academic failure and social isolation.[ncbi.nlm.nih.gov]
  • First-line treatment of diurnal somnolence is modafinil. Sodium oxybate is efficient for sleepiness, cataplexy and bad quality of night sleep. Prognosis Narcolepsy can severely disable scholarly and professional performances of the patients.[orpha.net]
Sleep Disturbance
  • Our findings add to further understanding of the structural basis of secondary narcolepsy, and may provide basis for future neuroimaging studies on sleep disturbances in traumatic brain injury (TBI).[ncbi.nlm.nih.gov]
  • It is likely that narcolepsy involves multiple factors interacting to cause neurological dysfunction and sleep disturbances.[web.archive.org]
  • OBJECTIVES: Narcolepsy is a neurological sleep disorder characterized by excessive daytime sleepiness and nighttime sleep disturbance.[ncbi.nlm.nih.gov]
  • Narcolepsy, a sleep disturbance that is characterized by sudden, uncontrollable spells of sleep during the day, with disturbances of sleep at night. The syndrome usually occurs in youth or early adult life.[britannica.com]
  • It is likely that narcolepsy involves multiple factors interacting to cause neurological dysfunction and sleep disturbances. Treatment There is no cure for narcolepsy. The U.S.[ninds.nih.gov]

Workup

Sleep studies are an essential part of the evaluation of patients with probable chances narcolepsy. An overnight polysomnogram (PSG) followed by a multiple sleep latency test (MSLT) can provide strongly suggestive evidence of narcolepsy while excluding other sleep disorders.

Human leukocyte antigen (HLA) typing may provide collateral data, but it is more useful for excluding the diagnosis by documenting that the patient does not have either DQB1*0602 or DQA1*0602.

Measurement of hypocretin (orexin) levels in the cerebrospinal fluid (CSF) may help establish the diagnosis [9]. CSF hypocretin levels lower than 110 pg/mL are included in the diagnostic criteria for narcolepsy in the second edition of the International Classification of Sleep Disorders (ICSD-2).

Imaging studies such as MRI are useful for excluding rare causes of symptomatic narcolepsy. Idiopathic narcolepsy may be seen in cases where there are structural abnormalities of the brainstem and diencephalon. MRI of brain in patients suffering from secondary narcolepsy, may show different abnormalities that can be related to the underlying cause.

Reduced Sleep Latency
  • Multiple sleep latency test showed multiple sleep onset REM periods with reduced sleep latency. When CMT1 and narcolepsy were coexist in an individual, the latter might be overlooked.[ncbi.nlm.nih.gov]
  • MSLT-like procedures have also been adapted to the canine species and have shown reduced sleep latency and REM latency in narcoleptic canines ( Nishino and Mignot 1997 ).[doi.org]
HLA-DR2
  • All the normal individuals (with or without HLA-DR2 or DQB1*0602) we have tested have detectable hypocretins in their CSF.[med.stanford.edu]
  • Narcolepsy was first shown to be tightly associated with HLA-DR2 (ref. 3 ) and later sublocalized to DQB1 * 0602 (ref. 4 ).[doi.org]
  • […] driving or while at work and prefer shift work as 'drowsiness' is more socially acceptable; it may also be accompanied by sleep paralysis Prevalence 1:600–Japan, 1:2400–US, 1:500, 000–Israel, : ratio 1:1, onset age 15– 35; 98-100% of narcoleptics have HLA-DR2[medical-dictionary.thefreedictionary.com]
  • In parallel narcolepsy studies across ethnic groups, Mignot’s lab found that it was not the initial HLA-DR2 allele that predisposed humans to narcolepsy, but another, nearby HLA gene, DQB1*0602. Humans are not like dogs.[the-scientist.com]

Treatment

Treatment of narcolepsy has two components i.e medical and auxiliary management. Good sleep hygiene is a must. Improvement is seen when the patients have a regular sleep schedule, which is generally 7.5-8 hours of sleep every night. Scheduled naps during the day also may help [18].

Pharmacologic treatment of narcolepsy involves the use of central nervous system (CNS) stimulants such as amphetamine, methylphenidate, modafinil, methamphetamine, and dextroamphetamine sulfate. With the help of these medicines daytime sleepiness can be reduced, thereby improving the symptoms in 65-85% of patients.

Tricyclic antidepressants such as protriptyline, imipramine and clomipramine, are effective for cataplexy. Sodium oxybate is highly effective for cataplexy, as it helps in improving night time sleep, which is often poor in narcolepsy. Selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) suppress REM sleep, thus helping to alleviate the symptoms of cataplexy, hypnotic hallucinations and sleep paralysis. They include fluoxetine and venlafaxine.

Prognosis

If the disease is managed and treated properly, then patients suffering from narcolepsy can have good life at home and work too. But if not treated, then it can be psychosocially disastrous [12].

Narcoleptic children may suffer from bad performance in school, social impairment, mocked by the colleagues, and there would be flaws in various activities seen in normal childhood development.

Etiology

The exact cause of narcolepsy isn't known. Narcolepsy has a genetic component and tends to run in families. An estimated 8 to 10% of people with narcolepsy have a close relative who has the disorder. Narcolepsy most likely involves a combination of genetics and one or more environmental provoking factors like infection, trauma, hormonal changes, immune system disorders, or stress.

Epidemiology

Narcolepsy affects about 1 in 2,000 people. The prevalence of narcolepsy in the US is 0.02-0.18%, which is comparable to that of multiple sclerosis [2] [3]. The frequency among first-degree relatives is 1-2%. Narcolepsy with cataplexy affects 0.02% of adults worldwide [4].

The male-to-female ratio in narcolepsy is 1.64:1. The disease has highest peak of occurrence at 15 years and a less marked peak at 36 years.

Sex distribution
Age distribution

Pathophysiology

Narcolepsy is considered to be an outcome of susceptible genes, defective neurotransmitter functioning and sensitivity, and aberrant immune modulation. Recent studies blame some human leukocyte antigen (HLA) subtypes and abnormal hypocretin (orexin) neurotransmission, that causes unexpected changes in monoamine and acetylcholine synaptic transmissions, and more accurately in the reticular activating system of the pons [5] [6].

The centrality of hypocretin transmission in the pathophysiology of narcolepsy was demonstrated when hypocretin knockout mice displayed cataplexy and sleepiness [7] [8]. Further evidence for impaired hypocretin functioning in humans was found with the discovery of low levels of hypocretin in the cerebrospinal fluid (CSF) of narcoleptic patients [9].

Subsequently, abnormal immune modulation was associated with the clinical development of narcolepsy in children in Scandinavia and Finland. It was found that the chances of narcolepsy increased to 8-12 folds in Finnish children after vaccination against the H1N1 influenza virus with a vaccine that used a potent ASO3 adjuvant. Every affected child who went through HLA typing was seen having the HLA DQB*0602 allele [10] [11].

Prevention

Narcolepsy cannot be prevented but the frequency of the narcolepsy episodes can be reduced in those suffering from it by avoiding the triggering factors or the conditions that causes the attack.

Summary

Narcolepsy is a chronic sleep disorder characterized by overwhelming daytime drowsiness and sudden bouts of sleep. It is difficult for a person suffering from narcolepsy to stay awake for long periods of time, whatever be the circumstances. It is characterized by the classic tetrad of excessive sleepiness during the daytime, cataplexy, hypnotic hallucinations, and sleep paralysis. It is also known as hypnolepsy, defined as a chronic neurological disorder caused by autoimmune destruction of hypocretin-producing neurons inhibiting the brain's ability to regulate sleep-wake cycles normally.[1]

Patient Information

Narcolepsy is a medical disorder characterized by excessive, sudden bouts of uncontrollable sleep during the day. These patients cannot sleep well at night and a polysomnogram is used to diagnose the condition.

The condition cannot be prevented as the exact cause is not understood but the symptoms can be controlled very well lifelong with medications like antidepressants, and stimulants. It is not a fatal condition but it can lead to accidents that are life-threatening.

Patients with narcolepsy should avoid heavy meals and alcohol. Patients should take scheduled short naps and participate in an exercise programs. They must avoid driving, operating heavy machinery, or any other activity that can have detrimental effect when sleepy. In one survey, almost 75% of patients with narcolepsy reported falling asleep while driving, and 56% reported nearly having accidents. In addition to these accidents, there are various other accidents that associated with narcolepsy like burns due to coming in close contact with hot objects, cuts from handling sharp objects, and breaking things. Patients with narcolepsy with cataplexy should wear a life preserver when engaged in water activities. They should not do water activities all by themselves. They should inform and also educate others about their cataplectic attacks.

People with narcolepsy have problems with memory, thinking, and attention. They suffer from emotional and social difficulties caused by their uncontrollable sleep episodes and cataplexy. They are prone to suffer from depression, severe emotional and social dysfunction in all areas, be it work, relationships or any relaxing activity. Generally it is seen that men with narcolepsy suffer from sexual problems.

References

Article

  1. Narcolepsy Information Page: National Institute of Neurological Disorders and Stroke (NINDS)". Ninds.nih.gov. 18 July 2013. Retrieved 3 March 2014.
  2. Longstreth WT Jr, Koepsell TD, Ton TG, Hendrickson AF, van Belle G. The epidemiology of narcolepsy. Sleep. 2007 Jan 1;30(1):13-26.
  3. Silber MH, Krahn LE, Olson EJ, Pankratz VS. The epidemiology of narcolepsy in Olmsted County, Minnesota: a population-based study. Sleep. 2002 Mar 15;25(2):197-202
  4. Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet. 2007 Feb 10;369(9560):499-511.
  5. Naumann A, Daum I. Narcolepsy: Pathophysiology and neuropsychological changes. Behav Neurol. 2003;14(3,4):89-98.
  6. Burgess CR, Scammell TE. Narcolepsy: neural mechanisms of sleepiness and cataplexy. J Neurosci. 2012 Sep 5;32(36):12305-11.
  7. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell. 1999 Aug 20;98(4):437-51.
  8. Diniz Behn CG, Klerman EB, Mochizuki T, Lin SC, Scammell TE. Abnormal sleep/wake dynamics in orexin knockout mice. Sleep. 2010 Mar;33(3):297-306.
  9. Mignot E, Lammers GJ, Ripley B, Okun M, et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol. 2002 Oct;59(10):1553-62.
  10. Partinen M, Saarenpää-Heikkilä O, Ilveskoski I, Hublin C, et al. Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland. PLoS One. 2012;7(3):e33723.
  11. Nohynek H, Jokinen J, Partinen M, Vaarala O, et al. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PLoS One. 2012;7(3):e33536.
  12. Douglas NJ. The psychosocial aspects of narcolepsy. Neurology. 1998 Feb;50(2 Suppl 1):S27-30.
  13. Vendrame M, Havaligi N, Matadeen-Ali C, Adams R, Kothare SV. Narcolepsy in children: a single-center clinical experience. Pediatr Neurol. 2008 May;38(5):314-20.
  14. Plazzi G, Serra L, Ferri R. Nocturnal aspects of narcolepsy with cataplexy. Sleep Med Rev. 2008 Apr;12(2):109-28.
  15. Palaia V, Poli F, Pizza F, Antelmi E, et al. Narcolepsy with cataplexy associated with nocturnal compulsive behaviors: a case-control study. Sleep. 2011 Oct 1;34(10):1365-71.
  16. Plazzi G, Pizza F, Palaia V, Franceschini C, et al. Complex movement disorders at disease onset in childhood narcolepsy with cataplexy. Brain. 2011 Dec;134:3480-92.
  17. Guilleminault C, Pelayo R. Narcolepsy in prepubertal children. Ann Neurol. 1998 Jan;43(1):135-42.
  18. Rogers AE, Aldrich MS, Lin X. A comparison of three different sleep schedules for reducing daytime sleepiness in narcolepsy. Sleep. 2001 Jun 15;24(4):385-91.

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Last updated: 2019-07-11 22:37