한국인 기면병 환자의 Human Leukocyte Antigen(HLA) DQB1*0602 발현 빈도

홍승철,우영섭,박수아,정종현,한진희,김린,이성필,Hong, Seung-Chul,Woo, Young-Sub,Park, Soo-A,Jeong, Jong-Hyun,Han, Jin-Hee,Kim, Leen,Lee, Sung-Pil 대한수면의학회 2001 수면·정신생리 Vol.8 No.2

목 적 : 본 연구는 기면병 환자와 정상 대조군에서 사람 백혈구 항원(human leukocyte antigen, 이하 HLA) DQB1*0602와 DR2의 발현 빈도를 조사하여 한국인 기면병 환자의 표지자로서의 가능성을 확인하고자 하였으며, 동시에 기면병 환자에서 나타나는 증상의 특성을 조사하였다. 방 법 : 야간수면 다원검사 및 입면잠복기 반복검사에서 입면잠복기의 평균값이 5분 이하이며, 최소 2회 이상의 수면시작 REM기(sleep onset REM periods)가 발생한 기면병 환자 20명(남자 11명, 여자 9명, 연령분포 $8{\sim}55$세, 평균연령 $28.2{\pm}13.0$세)과 정상 대조군 21명(남자 9명, 여자 12명, 연령분포 $21{\sim}39$세, 평균연령 $28.6{\pm}4.4$세)을 대상으로 하여 HLA typing을 시행하였다. 기면병의 제반 임상증상은 면담과 수면설문지를 통하여 수집하였다. 결 과 : 1) 기면병 환자군의 입면잠복기 반복 검사 결과 입면잠복기의 평균값은 $2.4{\pm}2.0$분이었으며, Sleep onset REM periods의 발생 평균 회수는 $3.0{\pm}1.6$회로 나타났다. 2) 기면병 환자군 모두에서 기면병의 주요 증상인 과도한 주간 졸리움 및 탈력발작을 나타냈고, 수면마비, 입면환각 및 야간수면장애는 각각 12명(60.0%), 14명(70.0%) 및 15명(75.0%)에서 발생하였다. 3) 탈력발작은 주로 감정적인 자극에 의하여 유발되어, 웃을때(80%, n=16)와 농담할 때(70%, n=14)에 가장 흔하게 유발되었으며, 탈력발작 발생부위의 빈도는 무릎과 다리 부분이 95%(n=19)이었으며, 턱부위는 30%(n=6)로 나타났다. 4) HLA-DQB1*0602는 환자군 20명중 18명(90.0%), 정상 대조군 21명중 5명(23.8%)에서 양성으로 나타났으며, HLA-DR2는 환자군 중 18명(90%), 정상 대조군 중 7명 (35%)에서 양성으로 나타났다. 결 론 : 이상의 결과에서 한국인 기면병 환자에서 HLADQB1*0602 양성이 높은 빈도로 나타났으며, 여러 인종들을 대상으로 한 여러 연구 결과와도 일치하여 HLA-DQB1*0602가 인종을 초월한 매우 유용한 표지자가 될 수 있을 것으로 생각된다. Introduction: Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy, is known to be closely associated with the human leukocyte antigen (HLA) DQB1*0602. Several studies have suggested that HLA-DQB1*0602 is strongly linked with narcolepsy-cataplexy. However, no studies have yet been made on whether HLA DQB1*0602 is associated with Korean patients with narcolepsy. This study was designed to investigate the frequency of HLA-DQB1*0602 of Korean patients with narcolepsy. Methods: Twenty patients were selected (mean age: $28.2{\pm}3.0$, 11 men and 9 women). The patients were confirmed to have narcolepsy by the overnight polysomnography and multiple sleep latency test (MSLT) in addition to their clinical history and symptoms at St. Vincent's Hospital and Korea University Hospital Sleep Disorders Clinic. Any subjects co-morbid with other hypersomnic sleep disorders such as sleep apnea or periodic limb movements during sleep were excluded. Clinical data was collected through a semi-structured interview for narcoleptic patients. All patients and 21 control did HLA typing for the presence of DQB1*0602. Results Obtained were as Follows: 1) Mean sleep latency was 2.4 (${\pm}2.0$ minutes) and mean frequency of sleep-onset REM period was 3.0 (${\pm}1.6$) by MSLT. 2) Characteristic symptoms of narcolepsy investigated were as follows: excessive daytime sleepiness (100%), cataplexy (100%), sleep paralysis (60%), hypnagogic hallucination (70%) and disrupted nocturnal sleep (75%). 3) Strong emotional expression such as laughing (80%) and joking (70%) triggered cataplexy which affects the knee and leg region (80%) and jaw region (30%). 4) HLA-DR2 was found in 90% of patients and 35% in controls. The frequency of HLA-DQB1*0602 in patients and controls was 90%, and 24%, respectively. Conclusions: These results, which exhibit high HLA-DQB1*0602 expression in Korean patients with narcolepsy, suggest that HLADQB1*0602 could be a strong genetic marker in narcolepsy.

두부외상으로 인해 발생한 기면증 1예

박성근,김진세,김린,정인과 大韓神經精神醫學會 2000 신경정신의학 Vol.39 No.1

본 증례는 두부 외상이후 갑작스런 근긴장의 소실을 보인 51세 남자 환자의 진단과정에 대한 보고이다. 환자는 하루 수십차례씩 갑자기 온몸이 마비된다는 증상을 호소하였으나, 의식은 명료하였고, 다칠 정도로 심하게 쓰러지는 경우도 없었으며, 특히 치료진과의 면담 중에 증상이 악화되는 양상을 보였다. 통상적인 검사실 검사와 뇌영상, 뇌기능 검사상 특이한 이상소견은 없었다. 우선 저자들은 전환장애나 꾀병을 먼저 의심하게 되었다. 그러나 자세한 병력청취와 관찰상 낮동안의 수면 발작과 야간 수면에서의 어려움이 있었고, 야간수면다원검사, 수면잠복기 반복검사, 그리고 탈력발작 심화 동안의 근전도 검사등을 통해 기면증으로 진단되었다. 또한 human leukocyte antigen(HLA)-DR2 검사에서 음성결과를 보여 본 환자의 기면증이 원발성이 아님이 시사되었다. 치료약물로 imipramine을 투여하자 탈력발작의 증상은 급격히 감소하였다. 따라서 두부외상 후 졸리움과 탈력발작의 증상에 대해 드물기는 하나, 진단과 치료에 있어 기면증의 가능성을 염두해 두어야 할 것이다. The authors reported a case and its diagnostic process of post-traumatic narcolepsy which had developed after a head trauma. The 51-years-old patient showed frequent generalized paralytic attack, which was aggravated during stressful situation, diet time, and in front of hospital staffs. During the paralytic attack, consciousness was alert, and he never collapsed to hurt. All laboratory findings including serum potassium level were within normal limit, and also brain imaging studies and electroencephalography revealed no specific abnormal findings. Our clinical impression was a conversion disorder or a malingering at first, but after the detailed history taking and the careful observation, daytime sleep attack and some sleep problems were revealed. Thus nocturnal polysomnography and multiple sleep latency test(MSLT) were performed, and then the authors could diagnose as "narcolepsy". HLA-DR2 typing was negative. After imipramine trial, the frequency and the intensity of attack was dramatically reduced. The authors concluded that narcolepsy should be considered in the differential diagnosis of sleepiness or transient loss of muscle tone after traumatic brain injury.

탈력발작 유무에 따른 기면병 환자의 비교 : 임상변인, HLA-DQB1*0602, Hypocretin

정종현,홍승철,신윤경,한진희,이성필 大韓神經精神醫學會 2007 신경정신의학 Vol.46 No.1

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 DQB 1 *0602 and CSF hypocretin levels in Korean narcolep-tics 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 Polysomno-graphy 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 DQB 1*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 ofHLA-DQB 1*0602 was found to be significantly increased (50 subjects, 89.3% vs. 8 subjects, 50.0%) (p=0.000). 2) tn 48 out of 56 cataplexy-positive patients (85.7%), hypocretin levels were decreased (≤110 pg/mI) 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, re-ported 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 seventy 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-DQB 1*0602, and lower hypocretin levels in cataplexy-positive groups than Cata-pelxy-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.

기면증 : 임상 양상, 진단 그리고 치료

신홍범,Shin, Hong-Beom 대한수면의학회 2010 수면·정신생리 Vol.17 No.2

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.

기면증 일예에 대한 다원수면검사 소견

서광윤,이성필,김 인,고재광 大韓神經精神醫學會 1993 신경정신의학 Vol.32 No.4

The authors experienced a patient who complained of excessive daytime sleepiness and cataplexy, and confirmed the diagnosis of narcolepsy through overnight polysomnography and Multiple Sleep Latency Test(MSLT). In overnigth polysomnography, total bed time was 491 minutes, total sleep time was 325 minutes and sleep efficiency was 66.2%. Sleep latency was 36 minutes and latency to REM sleep was 253 minutes. Fractions of each sleep stages by total sleep time were 54.5%(Stage 1), 19.4%(Stage 2), 15.7%(Stage 3+4), 10.5%(REM) respectively. Multiple Sleep Latency Test was performed at 10 : 00, 12 : 00, 14 : 00, 16 : 00. In the test, sleep latency was shortened by under 5 minutes at all of the 4 times test and Sleep Onset REM(SOREM), a characteristic polysomnographic feature of the narcolepsy, was observed two times at test 14 : 00 and 16 : 00. The authors reported the polysomnographic findings of a case of narcolepsy with literature review.

Suppression of Motor Evoked Potential and H-reflex during Cataplexy in Narcolepsy

한선정,주은연,김선하,정소희,홍승봉 대한수면연구학회 2007 Journal of sleep medicine Vol.4 No.2

Objectives: To investigate the electrophysiologic mechanism of cataplexy, the authors measured motor evoked potential (MEP) and H-reflex during asymptomatic, cataplectic and post-cataplectic periods in a narcolepsy patient. Methods: For MEP recording, transcranial magnetic stimulation (TMS) was applied to the right and left hemispheres using a Magstim 200 stimulator and a figure of 8-shaped coil. MEP amplitudes in resting state were measured at stimulus intensities of 120 and 150% of resting motor threshold (rMT). H-reflex was elicited by electrical stimuli on a tibial nerve. Results: rMT at baseline was 43% in the right and 39% in the left hemisphere. Mean MEP amplitude at baseline was 1.15 mV at a stimulation intensity of 120% rMT and 1.77 mV at 150% rMT. During a cataplectic episode, MEP amplitude abruptly decreased to 0.15 mV at 120% rMT and 0.18 mV at 150% rMT when the patient began to feel facial weakness and experience difficulty talking; subsequently no MEP was evoked during loss of whole body muscle tone. H-reflexes were well elicited during asymptomatic periods (mean amplitude: 2.55 mV at 10.0 mA) whereas H-reflex amplitude abruptly decreased and then disappeared after a cataplectic attack started. Conclusion: Suppression of both MEP and H-reflex during cataplexy indicates that postsynaptic spinal motor neuron inhibition is the main pathomechanism underlying cataplexy.