A Study of the Diagnostic Utility of HLA Typing, CSF Hypocretin-1 Measurements, and MSLT Testing for the Diagnosis of Narcolepsy in 163 Korean Patients With Unexplained Excessive Daytime Sleepiness

Hong, Seung‐Chul; Lin, Ling; Jeong, Jong-Hyun; Shin, Yongho; Han, Jin‐Hee; Lee, Ji‐Hyun; Lee, Sung-Pil; Zhang, Jing; Einen, Mali; Mignot, Emmanuel

doi:10.1093/sleep/29.11.1429

Cited by 60 publications

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“…Chinese patients with narcolepsy (with and without cataplexy) were heavier and younger than those with idiopathic hypersomnia (independent of age and sex). Most were male (67% for NC), a result consistent with other reports in Japan (60%) 7 , Korea (57%) 4 , France (67%) 9 , Canada (54%) 9 but not the United States (44%) 8 . Finally, there were few (1% to 2%) reports of familial clusters, and no difference related to age of onset for these few subjects.…”

Section: Discussionsupporting

confidence: 89%

“…These differences were most likely related to age alone rather than age of onset, as similar results were observed when patients were classified by puberty status at diagnosis (Table 4). Importantly, even though the mean number of SOREMPs was lower in very young subjects with narcolepsy, overall percentage positivity for the MSLT did not differ in this study (Tables 3,4). Only 4 of the 206 (1.9%) with prepubertal onset and one of the 60 (1.7%) with puberty onset had a family history of typical narcolepsy-cataplexy.…”

Section: Group Stratificationcontrasting

confidence: 50%

“…In China, there is a population prevalence of 0.034% in patients in South China presenting to sleep centers in Hong Kong 1,2 and a prevalence of 0.014% in Korean adolescents with similar clinical and biological presentations. [3][4][5] Studies in North America and Europe estimates are similar. As the origin and mechanisms that produce narcolepsy are not well understood, comparisons of clinical presentations in collections of several characterized patient groups can inform future studies of clinical and genetic epidemiology.…”

Section: Introductionmentioning

confidence: 78%

“…11 A focus 271 patients was defined either by the presence of documented hypocretin deficiency (n = 47; CSF hypocretin-1 ≤ 110 pg/ mL) or, if hypocretin deficiency was not documented through CSF studies (CSF hypocretin-1 unavailable), by the presence of clear cataplexy and HLA-DQB1*0602. Using this definition, approximately 98% of cases included are predicted to have hypocretin deficiency 4 if CSF hypocretin-1 had been measured in all subjects.…”

Section: Introductionmentioning

confidence: 99%

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Presentations of Primary Hypersomnia in Chinese Children

Han

et al. 2011

Sleep

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627Childhood Narcolepsy/Hypersomnia-Han et al on the pediatric population could help address issues related to puberty, genetic predisposition, and environmental triggers, and possibly shed light on factors that might delay diagnosis. We report on findings from a pediatric cohort of patients who presented with primary hypersomnia to a sleep clinic in Beijing, China over a period of ~10 years. All were evaluated in a standard fashion and classified as narcolepsy with or without cataplexy or idiopathic hypersomnia. Our purpose was to describe age of onset and clinical features of primary hypersomnia among a mainland Chinese cohort of children, and to compare the findings to the literature. METHODS PatientsPatients were children, defined as < 18 years of age, successively presenting with hypersomnia seen over a period of ~10 years (September, 1998 to May, 2009) at People's Hospital, Beijing University, Beijing. A total of 417 children (63%) were drawn from a population of 671 adults and children with hypersomnia. The hospital has a pulmonary medicine departmentbased sleep center, which sees both children and adults, and receives referrals from all of mainland China. It is estimated that 70% of the diagnosed narcolepsy patients in mainland China are seen at this center at People's Hospitals.12 A prior report focused on the impact of a narcolepsy recognition strategy in a pediatric neurology clinic, 13 whereas this report retrospectively describes a cohort with a broader symptom profile, evaluated using a stan- INTRODUCTIONNarcolepsy-cataplexy (NC) occurs worldwide. In China, there is a population prevalence of 0.034% in patients in South China presenting to sleep centers in Hong Kong 1,2 and a prevalence of 0.014% in Korean adolescents with similar clinical and biological presentations.3-5 Studies in North America and Europe estimates are similar. As the origin and mechanisms that produce narcolepsy are not well understood, comparisons of clinical presentations in collections of several characterized patient groups can inform future studies of clinical and genetic epidemiology.Narcolepsy-cataplexy is said to present in the second to third decade of life, with 70% to 80% of patients reporting onset between 10-20 years of age. Large sample size observations from the United States, Canada, Europe, and Japan report that half of adult patients with narcolepsy report narcolepsy onset prior to 15 years old, and only exceptionally at 5 or younger.6-9 Studies in the 1980s-1990s reported a median delay > 10 years between onset and diagnosis, 10 whereas a more recent report suggests the delay can be only a few years, particularly in children.11 A focus Objective: To retrospectively describe childhood presentations of primary hypersomnia with an emphasis on narcolepsy-cataplexy in a Chinese population. Methods: A total of 417 children (< 18 years old) successively presenting with complaints of hypersomnia without anatomic cause or sleep apnea risk were evaluated using the Stanford Sleep Inventory, human leukocyte antigen (HLA) ...

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Section: Discussionsupporting

confidence: 89%

Section: Group Stratificationcontrasting

confidence: 50%

Section: Introductionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

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Presentations of Primary Hypersomnia in Chinese Children

Han

et al. 2011

Sleep

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“…Methods for the cohort evaluation were reported in Hong et al, 35 although the sample has been continually extended through 2012. Of these 3 subjects, 2 were found to have clear cataplexy based on the DIGSAN and further review, and were included.…”

Section: Testing the Digsanmentioning

confidence: 99%

Dual Cases of Type 1 Narcolepsy with Schizophrenia and Other Psychotic Disorders

Cañellas

Lin

Juliá

et al. 2014

Journal of Clinical Sleep Medicine

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Objective: Cases of narcolepsy in association with psychotic features have been reported but never fully characterized. These patients present diagnostic and treatment challenges and may shed new light on immune associations in schizophrenia. Method: Our case series was gathered at two narcolepsy specialty centers over a 9-year period. A questionnaire was created to improve diagnosis of schizophrenia or another psychotic disorder in patients with narcolepsy. Pathophysiological investigations included full HLA Class I and II typing, testing for known systemic and intracellular/synaptic neuronal antibodies, recently described neuronal surface antibodies, and immunocytochemistry on brain sections to detect new antigens. Results: Ten cases were identifi ed, one with schizoaffective disorder, one with delusional disorder, two with schizophreniform disorder, and 6 with schizophrenia. In all cases, narcolepsy manifested fi rst in childhood or adolescence, followed by psychotic symptoms after a variable interval. These patients had auditory hallucinations, which was the most differentiating clinical feature in comparison to narcolepsy patients without psychosis. Narcolepsy therapy may have played a role in triggering psychotic symptoms but these did not reverse with changes in narcolepsy medications. Response to antipsychotic treatment was variable. Pathophysiological studies did not reveal any known autoantibodies or unusual brain immunostaining pattern. No strong HLA association outside of HLA DQB1*06:02 was found, although increased DRB3*03 and DPA1*02:01 was notable. Conclusion: Narcolepsy can occur in association with schizophrenia, with signifi cant diagnostic and therapeutic challenges. Dual cases maybe under diagnosed, as onset is unusually early, often in childhood. Narcolepsy and psychosis may share an autoimmune pathology; thus, further investigations in larger samples are warranted. Keywords: type 1 narcolepsy, psychotic disorders, HLA, brain autoantibodies, autoimmune Citation: Canellas F, Lin L, Julià MR, Clemente A, VivesBauza C, Ollila HM, Hong SC, Arboleya SM, Einen MA, Faraco J, Fernandez-Vina M, Mignot E. Dual cases of type 1 narcolepsy with schizophrenia and other psychotic disorders. J Clin Sleep Med 2014;10(9):1011-1018. S C I E N T I F I C I N V E S T I G A T I O N ST ype 1 narcolepsy is a disabling sleep disorder caused by hypocretin-1 defi ciency affecting approximately 0.02% of adults worldwide.1 It is strongly associated with the DQB1*06:02 allele of the human leucocyte antigen (HLA) system, 2 and is likely due to an autoimmune attack causing a specifi c loss of hypothalamic hypocretin-1 neurons.Narcolepsy is characterized by the presence of daytime sleepiness, cataplectic attacks, hypnagogic/hypnopompic hallucinations, sleep paralysis, and disturbed nocturnal sleep. Initially narcolepsy was considered a psychiatric disorder, as some symptoms are reminiscent of psychiatric disorders, for instance, disordered thinking and confusion-like behaviors due to sleepiness; and psychotic-like symptoms d...

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