Narcolepsia na infância: a atuação multidisciplinar com a psicologia do sono do diagnóstico ao tratamento em um relato de caso / Child narcolepsy: the multidisciplinary approach with sleep psychology from diagnostics to treatment in a case report / Narcolepsia en la infancia: actuación multidisciplinar con la psicología del sueño desde el diagnóstico hasta el tratamiento en un caso clínico

A narcolepsia, distúrbio neurológico crônico caracterizado pela sonolência diurna excessiva, pode ser associada à cataplexia, fragmentação do sono, alucinações relacionadas ao sono e paralisia do sono. Frequentemente, é confundida com outros transtornos, como Transtorno do Déficit de Atenção com Hiperatividade (TDAH), epilepsia e até esquizofrenia, assim, por vezes, é diagnosticada inadequadamente. Objetiva-se relatar o diagnóstico diferencial bem-sucedido da narcolepsia na infância e suas dificuldades, realizado por uma equipe multidisciplinar, enfocando a atuação da psicologia do sono em avaliação e intervenção. Um menino de 10 anos foi recebido no Ambulatório de Narcolepsia e Apneia do Sono Infantil (AMBNAP), alocado no Hospital Universitário Onofre Lopes da Universidade Federal do Rio Grande do Norte (UFRN) com queixas de sonolência diurna excessiva, sono fragmentado e episódios de perda de tônus muscular. Foi submetido a entrevistas psiquiátrica e psicológica pormenorizadas, a exames, aplicação de escalas específicas para rastreio e diagnóstico de transtornos de sono e diário de sono, solicitação de recursos de mídia e de relatório escolar e avaliação neurológica. A partir da investigação multidisciplinar, o diagnóstico foi de Narcolepsia e Síndrome da Apneia Obstrutiva do Sono (SAOS). O paciente foi submetido a técnicas da Terapia Cognitivo-Comportamental (TCC) e segue em acompanhamento, apresentando resultados satisfatórios. Este estudo evidencia que uma equipe multidisciplinar especializada na área de sono atuando em conjunto com a Psicologia do Sono oportuniza o diagnóstico e intervenções precoces eficazes para o tratamento do distúrbio do sono na infância.(AU)

Narcolepsy is a chronic neurologic disorder characterized by excessive daytime sleepiness which can be associated with cataplexy, sleep fragmentation, sleep-related hallucinations, and sleep paralysis. This sleep disorder is often confused with other disorders such as Attention Deficit Hyperactivity Disorder (ADHD), epilepsy, and even schizophrenia, and is, thus, misdiagnosed. This study aims to report the successful differential diagnosis for childhood narcolepsy carried out by a multidisciplinary team and its challenges, with a focus on the role of sleep psychology in assessment and intervention. A 10-year-old child was received at the Child Narcolepsy and Sleep Apnea Clinic (AMBNAP), located at the Onofre Lopes University Hospital of the Federal University of Rio Grande do Norte (UFRN), with complaints of hypersomnolence, fragmented sleep, and episodes of loss of muscle tone. He underwent detailed psychiatric and psychological interviews, analysis of exams, application of specific scales for screening and diagnosis of sleep disorders and sleep diary, request of media resources and school report, and neurological assessment. From the multidisciplinary investigation, excluding of other neurological diagnoses, the diagnosis was Narcolepsy and Obstructive Sleep Apnea Syndrome (OSAS). The patient was submitted to Cognitive Behavioral Therapy (CBT) techniques, such as psychoeducation, scheduled naps, cognitive therapy for dysfunctional beliefs, and sleep hygiene strategies, and continues to be followed up, with satisfactory results since the first two months of intervention. The findings presented in this study show that a multidisciplinary team specialized in the sleep area, acting alongside Sleep Psychology provides early diagnosis and interventions for the sleep disorder treatment in childhood.(AU)

La narcolepsia es un trastorno neurológico crónico caracterizado por somnolencia diurna excesiva que puede asociarse con cataplejía, fragmentación del sueño, alucinaciones relacionadas con el sueño y parálisis del sueño. El trastorno del sueño a menudo se confunde con otros trastornos como el TDAH, la epilepsia e incluso la esquizofrenia, y se diagnostica erróneamente. El objetivo es presentar el diagnóstico diferencial exitoso de la narcolepsia en la infancia y sus dificultades, realizado por un equipo multidisciplinario, con foco en el papel de la psicología del sueño en la evaluación e intervención. El estudiante de 10 años fue recibido en la Clínica de Narcolepsia Infantil y Apnea del Sueño (AMBNAP), ubicada en el Hospital Universitario Onofre Lopes de la Universidad Federal de Rio Grande do Norte, con quejas de hipersomnolencia, sueño fragmentado y episodios de pérdida de tono muscular. Se sometió a entrevistas psiquiátricas y psicológicas detalladas, análisis de exámenes, aplicación de escalas específicas para la detección y diagnóstico de trastornos del sueño y el diario del sueño, solicite recursos de medios y informe escolar y evaluación neurológica. La investigación multidisciplinaria, el diagnóstico fue Narcolepsia y SAOS. El paciente fue sometido a técnicas de terapia cognitivo-conductual (TCC), como psicoeducación, siestas programadas, terapia cognitiva por creencias disfuncionales y estrategias de higiene del sueño, y se le dio seguimiento con resultados satisfactorios. Los resultados demostraron que un equipo multidisciplinario especializado en el campo del sueño, actuando en conjunto con la psicología del sueño, proporciona el diagnóstico y las intervenciones tempranas para el trastorno del sueño de la narcolepsia en la infância.(AU)

Recent Updates on Narcolepsy and Hypersomnia / 신경정신의학

Narcolepsy is a chronic neurological sleep disorder caused by hypocretin neuron loss, resulting in excessive daytime sleepiness, disturbed nocturnal sleep, and intrusions of aspects of rapid eye movement sleep in wakefulness, such as cataplexy, sleep paralysis, and hypnopompic/hypnagogic hallucinations. Narcolepsy disrupts the maintenance and orderly occurrence of the wake and sleep stages. Cataplexy is a highly specific symptom of narcolepsy, but many other symptoms can be observed in a variety of sleep disorders. The diagnosis of narcolepsy type 1 requires a history of excessive daytime sleepiness and one of the following : 1) a low cerebrospinal fluid hypocretin-1 level or 2) cataplexy and a positive multiple sleep latency test result. The diagnosis of narcolepsy type 2 requires a history of excessive daytime sleepiness and a positive mean sleep-latency test result. The mean sleep-latency test must be preceded by nighttime polysomnography to exclude other sleep disorders and to document adequate sleep. The mean sleep-latency test result can be falsely positive in other sleep disorders, such as shift work, sleep apnea, or sleep deprivation, and it is influenced by age, sex, and puberty. Modafinil and armodafinil can reduce the excessive daytime sleepiness without many of the side effects associated with older stimulants. Although there is no cure for narcolepsy, the treatments are often effective and include both behavioral and pharmacologic approaches.

Niemann-Pick Disease Type C Misdiagnosed as Cerebral Palsy: A Case Report

Niemann-Pick disease type C (NP-C) is a rare autosomal recessive neurovisceral lysosomal lipid storage disorder. The clinical manifestations of the disorder are variable. This report describes the case of a 27-month-old girl with NP-C whose condition had been misdiagnosed as spastic cerebral palsy (CP). She had spasticity, particularly at both ankles, and gait disturbance. Magnetic resonance imaging of the brain revealed findings suspicious of sequelae from a previous insult, such as periventricular leukomalacia, leading to the diagnosis of CP. However, she had a history of hepatosplenomegaly when she was a fetus and her motor development had deteriorated, with symptoms of vertical supranuclear gaze palsy, cataplexy, and ataxia developing gradually. Therefore, NP-C was considered and confirmed with a genetic study, which showed mutation of the NPC1 gene. Thus, if a child with CP-like symptoms presents with a deteriorating course and NP-C-specific symptoms, NP-C should be cautiously considered.

Parasomnia as an Initial Presentation of Narcolepsy

Narcolepsy is characterized by excessive daytime sleepiness, cataplexy, sleep paralysis and hypnagogic hallucinations. Only a few studies have focused on non-rapid eye movement (NREM) and REM parasomnias in narcolepsy. We report a narcolepsy without cataplexy patient presenting parasomnia as an initial symptom. A 18-year-old boy was admitted to hospital for abnormal behavior of sitting up during sleep over 2 years. He had a symptom of lethargy without cataplexy and subjective excessive daytime sleepiness, but his family found him often asleep during daytime. He underwent 3 times of polysomnography (PSG) including 1 multiple sleep latency test (MSLT) after the last PSG. The last PSG showed 1 episode of abrupt sitting. Three sleep REM onset period was observed in MSLT which was not detect in PSG. Parasomnia as an initial symptom of narcolepsy is a rare clinical entity. The MSLT may be useful in the evaluation of patients with parasomnia and unexplained hypersomnia.

Comparison of Health Related Quality of Life between Type I and Type II Narcolepsy Patients

OBJECTIVES: Narcolepsy with cataplexy is a rare chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic/hypnopompic hallucinations. The aims of the present study were comparing the health-related quality of life (HR-QOL) of patients with type I and type II narcolepy patients, and determining the factors that influence the HR-QOL in narcolepsy patients. METHODS: All patients performed night polysomnography (PSG) and multiple sleep latency test (MSLT). HR-QOL and the severity of subjective symptoms were evaluated using various questionnaires, including the Korean versions of the Medical Outcome Study Short Form-36, the Pittsburg Sleep Quality Index-Korean version, the Korean version Epworth Sleepiness Scale, and the Korean version Beck Depression Inventory-2. RESULTS: We enrolled 21 type I narcolepsy patients and 27 type II patients. Type I patients had short rapid eye movement (REM) latency on night PSG and more sleep onset REM periods on MSLT. The total score of HR-QOL was worse in patients with type I narcolepsy than in the type II narcolepsy patients. There was association between the severities of excessive daytime sleepiness, depression and the degree of worsening of QOL. CSF hypocretin level had no correlation with the scores of HR-QOL. CONCLUSIONS: These findings demonstrate that type I narcolepsy patients are sleepier, depressive, and have more burden on the HR-QOL. And the impairment in QOL of narcolepsy patients is related to the degree of excessive daytime and depressive mood.

Clinical effect of atomoxetine hydrochloride in 66 children with narcolepsy / 中华儿科杂志

<p><b>OBJECTIVE</b>To observe the efficacy and safety of atomoxetine hydrochloride in children with narcolepsy.</p><p><b>METHOD</b>Totally 66 patients with narcolepsy who were conformed international classification of sleep disturbances (ICSD-2) diagnostic criteria treated with atomoxetine hydrochloride seen from November 2010 to December 2014 were enrolled into this study, 42 of them were male and 24 female, mean age of onset was 7.5 years (3.75-13.00 years), mean duration before diagnosis was 1.75 years (0.25-5.00 years). Complete blood count, liver and kidney function, multiple sleep latency test (MSLT), polysomnography (PGS), neuroimaging and electroencephalography (EEG) were performed for each patient. For some of the children HLA-DR2 gene and serum markers of infection were tested. The 66 cases were followed up from 2 to 49 months (average 18 months) to observe the clinical efficacy and adverse reactions.</p><p><b>RESULTS</b>In 62 cases excessive daytime sleepiness was improved, in 11 cases (16.7%) it was controlled (16.7%), in 29 cases (43.9%) the treatment was obviously effective and in 22 (33.3%) it was effective; cataplexy occurred in 54 cases, in 18 (33.3%) it was controlled, in 19 (35.2%) the treatment was obviously effective and in 10 (18.5%) effective; night sleep disorders existed in 55 cases, in 47 cases it was improved, in 14 (25.5%) it was controlled, in 20 (36.4%) the treatment was obviously effective and in 13 (23.6%) effective; hypnagogic or hypnopompic hallucination was present in 13 cases, in only 4 these symptoms were controlled. Sleep paralysis existed in 4 cases, it was controlled in only 1 case. In 18 cases attention and learning efficiency improved.Anorexia occurred in 18 cases, mood disorder in 5 cases, depression in 2 cases, nocturia, muscle tremors, involuntary tongue movement each occurred in 1 case. P-R interval prolongation and atrial premature contraction were found in 1 case.</p><p><b>CONCLUSION</b>Atomoxetine hydrochloride showed good effects in patients with narcolepsy on excessive daytime sleepiness, cataplexy and night sleep disorders, the effects on hallucinations and sleep paralysis were not significant. Adverse reactions were slight, anorexia and mood disorder were common. As a non-central nervous system stimulant, atomoxetine hydrochloride does not induce drug dependence and has no prescription limits; it has good tolerability, safety and effectiveness, it can be a good alternative in treatment of children with narcolepsy.</p>

Evaluation of Cognitive Functions in Patients with Narcolepsy / 農村醫學 地域保健

OBJECTIVE: This study aimed to evaluate attention, memory and executive function in patients with narcolepsy. METHODS: This study included 23 narcoleptic patients whose diagnosis were confirmed by the International Classification of Sleep Disorders(ICSD) at Chonnam National University Hospital Sleep Disorders Clinic or an other hospital in Korea, from 2005 to 2008, as well as 23 normal controls. All participants were given an IQ test for Korean-Wechsler Adult Intelligence Scale and several neuropsychological function tests (the d2 test for attention function, the Rey Complex Figure Test for nonverbal memory, the Korean-California Verbal Learning Test [K-CVLT] for verbal memory, and the Wisconsin Card Sorting Test for executive function). Clinical features of narcoleptic patients, including the frequency of excessive daytime sleepiness, cataplexy, sleep paralysis and hypnagogic hallucination, were investigated by a structured clinical interview administered by a neuropsychiatist. Excessive daytime sleepiness was evaluated by the Epworth sleepiness scale. RESULTS: Characteristic symptoms of narcolepsy observed in this study included excessive daytime sleepiness (n=23, 100.0%), cataplexy (n=19, 82.6%), hypnagogic hallucination (n=5, 21.7%) and sleep paralysis (n=12, 52.2%). In nocturnal polysomnographic findings, stage 2 sleep and REM latency were found to be significantly decreased in narcoleptic patients compared with the control group, and were accompanied by significant increases in stage 1 sleep. Narcoleptic patients had lower scores than the control group on total number, Total Number-Total Error, Concentration Performance and Fluctuation Rate on the d2 test, which measures attention. Also, there were significant differences between the performance of patient and control groups on the B list of the K-CVLT, which measures verbal memory. CONCLUSION: Narcoleptic patients showed decreased attention and verbal memory performance compared to the control group; however, in many areas, narcoleptic patients still demonstrated normal cognitive function.

Effect of clomipramine in a dog with cataplexy / 대한수의학회지

A 5-year-old, castrated male, Maltese was presented with history of acute flaccid paralysis. The dog was presented with sudden loss of muscle tone and involuntary movements of hind limbs. Neurologic examination revealed reduced postural reaction in the bilateral hind limbs. MRI of brain showed moderate hydrocephalus, but other examination results were normal. Based on the characteristic episodes and examination results, canine cataplexy was suspected. Treatment was initiated with clomipramine as cataplexy control. Clinical signs resolved with 3-month medication. This case demonstrates therapeutic diagnosis of cataplexy. To the author's knowledge, this is the first report of cataplexy treating with clomipramine.

Late-Onset Narcolepsy with Cataplexy Unresponsive to Intravenous High-Dose Immunoglobulin Treatment

Narcolepsy with cataplexy (NC) is associated with hypocretin deficiency, and is thought to be an autoimmunity condition. The mean age at onset is estimated to be in the early 20s. Recent papers have addressed the response to immunotherapies in NC, with challenging results. We report a case of late-onset NC in a patient who did not benefit from early intravenous high-dose immunoglobulin (IVIg) therapy. This is the first reported attempt at using IVIg to treat an NC patient in Korea.

Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

BACKGROUND: Narcolepsy is a neurologic disorder characterized by excessive daytime sleepiness, symptoms of abnormal rapid eye movement (REM) sleep, and a strong association with HLA-DRB1*1501, -DQA1*0102, and -DQB1*0602. Here, we investigated the clinico-physical characteristics of Korean patients with narcolepsy, their HLA types, and the clinical utility of high-resolution PCR with sequence-specific primers (PCR-SSP) as a simple typing method for identifying DRB1*15/16, DQA1, and DQB1 alleles. METHODS: The study population consisted of 67 consecutively enrolled patients having unexplained daytime sleepiness and diagnosed narcolepsy based on clinical and neurological findings. Clinical data and the results of the multiple sleep latency test and polysomnography were reviewed, and HLA typing was performed using both high-resolution PCR-SSP and sequence-based typing (SBT). RESULTS: The 44 narcolepsy patients with cataplexy displayed significantly higher frequencies of DRB1*1501 (Pc= 0.003), DQA1*0102 (Pc=0.001), and DQB1*0602 (Pc=0.014) than the patients without cataplexy. Among patients carrying DRB1*1501-DQB1*0602 or DQA1*0102, the frequencies of a mean REM sleep latency of less than 20 min in nocturnal polysomnography and clinical findings, including sleep paralysis and hypnagogic hallucination were significantly higher. SBT and PCR-SSP showed 100% concordance for high-resolution typing of DRB1*15/16 alleles and DQA1 and DQB1 loci. CONCLUSIONS: The clinical characteristics and somnographic findings of narcolepsy patients were associated with specific HLA alleles, including DRB1*1501, DQA1*0102, and DQB1*0602. Application of high-resolution PCR-SSP, a reliable and simple method, for both allele- and locus-specific HLA typing of DRB1*15/16, DQA1, and DQB1 would be useful for characterizing clinical status among subjects with narcolepsy.

Narcolepsy in Children / 수면정신생리

Childhood narcolepsy is one of the underdiagnosed diseases even the first symptoms often appear in childhood. Making diagnosis through history taking is not always easy because the symptoms of childhood narcolepsy are different from those of adulthood. Diagnostic laboratory tests such as sleep studies, tests for human leukocyte antigens, cerebrospinal fluid hypocretin measurement should be considered when the child has excessive daytime sleepiness without cataplexy. Treatment approach should be start as early as possible to avoid secondary academic, emotional difficulties. Both pharmacological and non-pharmacological management, and close cooperation between parents and school teachers should be maintained. In the near future, childhood narcolepsy can be a key to understand the pathogenesis of narcolepsy.

Excessive Daytime Sleepiness Case Confounding with Thyrotoxicosis / 수면정신생리

Narcolepsy is a sleep disorder, which is characterized by excessive daytime sleepiness (EDS) that is typically associated with cataplexy, sleep fragmentation and other REM sleep-related phenomenon such as sleep paralysis and hypnagogic hallucination. Narcoleptic symptoms can be developed from various medical or neurological disorders. A 17-year-old male patient admitted for the evaluation of EDS which started three-month ago. He slept more than 18 hours a day with cataplexy and hypnagogic hallucination. He was obese with body mass index (BMI) of 30.4 kg/m2. After admission he was newly diagnosed to the thyrotoxicosis. T3 391.2 ng/dL (60-181), free T4 4.38 ng/dL (0.89-1.76), TSH <0.01 microIU/mL (0.35-5.5) were measured. His pulse rate ranged 70-90 beats per minute and blood pressure ranged 150/100-120/70 mmHg. Polysomnography revealed many fragmentations in sleep with many positional changes (81 times/h). Sleep onset latency was 33.5 min, sleep efficiency was 47.9%, and REM latency from sleep onset was delayed to 153.6 min. REM sleep percent was increased to 27.1%. Periodic limb movement index was 13.4/h. In the multiple sleep latency test (MSLT), average sleep latency was 0.4 min and there were noted 3 SOREMPs (Sleep Onset REM sleep period) on 5 trials. We couldn't discriminate the obvious sleep-wake pattern in the actigraph and his HLA DQB1 *0602 type was negative. His thyroid function improved following treatment with methimazole and propranolol. Vital sign maintained within normal range. Cataplexy was controlled with venlafaxine 75 mg. Subjective night sleep continuity and PLMS were improved with clonazepam 0.5 mg, but the EDS were partially improved with modafinil 200-400 mg. Thyrotoxicosis might give confounding role when we were evaluating the EDS, though sleep fragmentation was one of the major symptoms of narcolepsy, but enormous amount of it made us think of the influence of thyroid hormone. The loss of sleep-wake cycle, limited improvement of EDS to the stimulant treatment, and the cataplexy not supported by HLA DQB1 *0602 should be answered further. We still should rule out idiopathic hypersomnia and measuring CSF hypocretin level would be helpful.

Traditional biomarkers in narcolepsy: experience of a Brazilian sleep centre / Biomarcadores tradicionias em narcolepsia: experiência de um centro de sono brasileiro

This study was thought to characterized clinical and laboratory findings of a narcoleptic patients in an out patients unit at São Paulo, Brazil. METHOD: 28 patients underwent polysomnographic recordings (PSG) and Multiple Sleep Latency Test (MSLT) were analyzed according to standard criteria. The analysis of HLADQB1*0602 allele was performed by PCR. The Hypocretin-1 in cerebral spinal fluid (CSF) was measured using radioimmunoassay. Patients were divided in two groups according Hypocretin-1 level: Normal (N) - Hypocretin-1 higher than 110pg/ml and Lower (L) Hypocretin-1 lower than 110 pg/ml. RESULTS: Only 4 patients of the N group had cataplexy when compared with 14 members of the L group (p=0.0002). DISCUSSION: This results were comparable with other authors, confirming the utility of using specific biomarkers (HLA-DQB1*0602 allele and Hypocretin-1 CSF level) in narcolepsy with cataplexy. However, the HLADQB1*0602 allele and Hypocretin-1 level are insufficient to diagnose of narcolepsy without cataplexy.

Este estudo foi idealizado para avaliar as características clinicas e laboratoriais de uma população de narcolépticos atendidos num centro de referência na cidade de São Paulo (Brasil). MÉTODO: 28 pacientes realizaram polissonografia e teste de múltiplas latências do sono segundo critérios internacionais. O alelo HLADQB1*0602 foi identificado por PCR. A Hipocretina-1 no líquido cefalorradiano (LCR) foi mensurada por radioimunoensaio. Os pacientes foram divididos em 2 grupos conforme o nível de Hipocretina-1. Normal (N) - Hypocretin-1 >110pg/ml e baixa (B) - Hypocretina-1 <110pg/ml. RESULTADOS: Somente 4 pacientes do grupo N tinham cataplexia quando comparados com 14 pacientes do grupo B (p=0,0002). DISCUSSÃO: Estes resultados foram comparáveis com outros autores, confirmando a utilidade do uso de biomarcadores específicos (HLA-DQB1*0602 e nível da hipocretina-1 no LCR) em narcolepsia com cataplexia. Porém, o alelo HLADQB1*0602 e a dosagem da Hipocretina-1 são insuficientes para o diagnóstico da narcolepsia sem cataplexia.

Narcolepsy: Clinical features, co-morbidities & treatment.

Narcolepsy is a neurologic illness that typically begins in the second and third decades of life. It is chronic in nature and negatively impacts the quality of life of affected patients. The classic presentation is a tetrad of excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. The exact cause remains unknown, but there is significant evidence that hypocretin deficiency plays an integral role. Some primary conditions that result in secondary narcolepsy include traumatic brain injury, congenital disorders, tumours, and strokes. Some medical and psychiatric disorders share characteristics of narcolepsy, at times leading to diagnostic inaccuracy. Other sleep disorders are commonly co-morbid. Diagnosis relies on patient history and objective data gathered from polysomnography and multiple sleep latency testing. Treatment focuses on symptom relief through medication, education, and behavioural modification. Both classic pharmacological treatments as well as newer options have significant problems, especially because of side effects and abuse potential. Novel modalities are being examined to expand options for treatment.

Narcolepsy: Clinical Feature, Diagnosis and Treatment / 수면정신생리

Narcolepsy is a central neurologic system disease. It begins early in life with disabling symptoms including excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucination and nocturnal sleep fragmentation. Patient with typical symptoms of narcolepsy is diagnosed by objective data from nocturnal polysomnography and multiple sleep latency tests. Narcolepsy is controlled with various medications. Nowadays, modafinil with favorable side effects profiles compared with traditional stimulant is mainly used. Gamma hydroxyl butyrate is effective in cataplexy. Cataplexy is also controlled with antidepressant such as Venlafaxine, SSRI, and TCA. As the knowledge of pathophysiology of narcolepsy expands, new treatment including immunological method, application of hypocretin and histamine systems have been tried.

Gray Matter Concentration Abnormality in Brains of Narcolepsy Patients

OBJECTIVE: To investigate gray matter concentration changes in the brains of narcoleptic patients. MATERIALS AND METHODS: Twenty-nine narcoleptic patient with cataplexy and 29 age and sex-matched normal subjects (mean age, 31 years old) underwent volumetric MRIs. The MRIs were spatially normalized to a standard T1 template and subdivided into gray matter, white matter, and cerebrospinal fluid (CSF). These segmented images were then smoothed using a 12-mm full width at half maximum (FWHM) isotropic Gaussian kernel. An optimized voxel-based morphometry protocol was used to analyze brain tissue concentrations using SPM2 (statistical parametric mapping). A one-way analysis of variance was applied to the concentration analysis of gray matter images. RESULTS: Narcoleptics with cataplexy showed reduced gray matter concentration in bilateral thalami, left gyrus rectus, bilateral frontopolar gyri, bilateral short insular gyri, bilateral superior frontal gyri, and right superior temporal and left inferior temporal gyri compared to normal subjects (uncorrected p < 0.001). Furthermore, small volume correction revealed gray matter concentration reduction in bilateral nuclei accumbens, hypothalami, and thalami (false discovery rate corrected p < 0.05). CONCLUSION: Gray matter concentration reductions were observed in brain regions related to excessive daytime sleepiness, cognition, attention, and memory in narcoleptics with cataplexy.

Pediatric Narcolepsy: Diagnosis and Treatment

Narcolepsy is chronic devastating disease that characterized by excessive daytime sleepiness, cataplexy, which often precipitated by intense emotion or excitement, hypnagogic, or hypnapompic hallucinations, sleep paralysis and nocturnal disrupted sleep. In child onset narcolepsy, the presentations of narcolepsy can be very variable, making misdiagnosis as seizure disorders or delaying diagnosis as much as several years after disease onset. For the diagnosis of narcolepsy, overnight polysomnography(PSG) and multiple sleep latency test(MSLT) should be evaluated. Test for Cerebrospinal fluid hypocretin(orexin) concentration and human leukocyte antigens(HLA) would be great helpful to confirm the narcolepsy with cataplexy even in early stage of disease in children. The mainstays of treatment are that reducing the excessive daytime sleepiness, preventing the intrusion of the REM related phenomena including cataplexy and consolidating the nighttime sleep. Central nervous system stimulators such as methylphenidate or amphetamine decrease excessive daytime sleepiness and tricyclic antidepressant(TCA) or selective serotonin reuptake inhibitors(SSRI) can prevent cataplexy. Recently, new therapeutic agents such as modafinil and sodium oxybate are emerging in clinical practice with much effectiveness. Counseling for poor school performance, social isolation and depression should be provided. Early diagnosis and treatment can greatly improve the quality of life. Awareness of excessive daytime sleepiness in children or adolescent will allow pediatricians to effectively identify hypersomnia such as narcolepsy.

HLA-DQB1 Allele and Hypocretin in Korean Narcoleptics with Cataplexy

Cataplexy is one of the most pathognomonic symptoms in narcolepsy. This study was designed to investigate the frequency of the HLA-DQB1 allele and cerebrospinal fluid (CSF) hypocretin levels in Korean narcoleptics with cataplexy as compared with those who do not have cataplexy. Seventy-two narcoleptics were selected based on polysomnography and multiple sleep latency test as well as their history and clinical symptoms at Sleep Disorders Clinic. The patients were divided into a narcolepsy with cataplexy group (n=56) and a narcolepsy without cataplexy group (n=16). All patients were subjected to HLA typing to determine the frequency of DQB1 allele and to spinal tapping to measure the level of CSF hypocretin. In cataplexy-positive patients, as compared with cataplexy-negative patients, the frequency of HLA-DQB1*0602 was found to be significantly high (89.3% vs. 50.0%) (p=0.003). On the other hand, the frequency of HLA-DQB1*0601 was found to be significantly low (0% vs. 43.8%) (p<0.001). In 48 of 56 cataplexy-positive patients (85.7 %), hypocretin levels were decreased (< or =110 pg/mL). However, only 6 of 16 cataplexy-negative patients (37.5%) exhibited a decreased hyopcretin level (p<0.001). The high frequency of HLA-DQB1*0602, low frequency of HLA-DQB1*0601 and low hypocretin levels in cataplexy-positive groups suggest that cataplexy-positive narcolepsy might be an etiologically different disease entity from the cataplexy-negative.

Comparison of Narcolepsy with Cataplexy and without Cataplexy: Clinical Variables, HLA-DQB1*0602, and Hypocretin / 신경정신의학

OBJECTIVES: Narcolepsy is a sleep disorder, characterized by excessive daytime sleepiness, cataplexy, sleep paralysis and hypnagogic hallucination. Among these symptoms, cataplexy is one of the most pathognomonic symptoms in narcolepsy. This study was designed to investigate the clinical features, frequency of DQB1*0602 and CSF hypocretin levels in Korean narcoleptics with cataplexy to compare with those who have not cataplexy. METHODS: From August 2003 to July 2005, we selected 72 patients who have narcolepsy confirmed by nocturnal polysomnography and multiple sleep latency test (MSLT) as well as their history and clinical symptoms at Sleep Disorders Clinic of St. Vincent's Hospital, Catholic University of Korea. Patients were divided into 56 cataplexy-positive group (narcolepsy with cataplexy group) and 12 cataplexy-negative group (narcolepsy without cataplexy group). HLA typing was done in all patients for the presence of DQB1*0602, and patients received spinal tapping to measure the level of CSF hypocretin. Clinical variables were examined by semi-structured interview for narcolepsy patients. RESULTS: 1) In cataplexy-positive group, compared with cataplexy-negative group, the frequency of HLA-DQB1*0602 was found to be significantly increased (50 subjects, 89.3% vs. 8 subjects, 50.0%)(p=0.000). 2) In 48 out of 56 cataplexy-positive patients (85.7%), hypocretin levels were decreased (< or =110 pg/ml) or were below the detection limit of assay (<40 pg/ml). However, only 6 out of 16 cataplexy-negative patients (37.5%) exhibited decreased hyopcretin level. The difference between two groups were statistically significant (p=0.000). 3) Cataplexy-positive group, compared to cataplexy-negative group, reported more frequent hypnagogic hallucinations (36 subjects, 64.3% vs. 4 subjects, 25.0%)(p=0.005). However, there were no significant differences in frequency or severity of daytime sleepiness, sleep paralysis and demographic data. 4. In nocturnal polysomnography and MSLT findings, there were no significant differences in all sleep parameters between two groups. CONCLUSION: Higher frequency of HLA-DQB1*0602, and lower hypocretin levels in cataplexy-positive groups than catapelxy-negatives suggest that narcoleptics with cataplexy might be a etiologically different disease entity from narcoleptics without cataplexy. Additionally, Current criteria prevail for the diagnosis of narcolepsy need to be reclassified according to the presence of cataplexy or not.

The effects of modafinil on clinical features and sleep structure of narcolepsy patients and healthy controls / 수면정신생리

INTRODUCTION: Excessive daytime sleepiness and cataplexy are key features of narcolepsy. Modafinil is psychostimulant used in the treatment of narcolepsy. In this study, we evaluated effects of modafinil on nocturnal sleep structure and sleep latency in multiple sleep latency test and clinical features. METHODS: Twelve narcoleptic patients (7 male, age: 22.9 +/- 2.6 yrs) were participated in the study. All of them had done nocturnal polysomnography (nPSG), multiple sleep latency test (MSLT), clinical symptoms scales and have repeated same procedure after taking 200 mg of modafinil. We have done linear mixed model analysis to describe effects of group, medication and nap time on these measures. RESULTS: Modafinil did not affect clinical scales except PSQI which had been reduced after medication. In this study, Modafinil reduced total sleep time, sleep efficiency and increased wake after sleep onset and percent of arousal during sleep in nocturnal polysomnography and prolonged mean sleep latency in multiple sleep latency tests in both group. DISCUSSION: Modafinil has stimulant effect of central nervous system but its effect on night sleep is less than other psychostimulants such as methylphenidate. We ascertained that modafinil affected total sleep time, sleep efficiency and percent of wake during sleep but did not effect on sleep structure. Modafinil was effective in the management of day time sleepiness. Modafinil can enhance alertness of control group without day time sleepiness.