Kleine-Levin syndrome: A systematic study of 108 patients
Kleine-Levin syndrome: A systematic study of 108 patients
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DOI：
10.1002/ana.21333
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发表时间：
2008-04-01
影响因子：
11.2
通讯作者：
Mignot, Emmanuel
中科院分区：
文献类型：
--
作者：
Arnulf, Isabelle;Lin, Ling;Mignot, Emmanuel
目的：Kleine-Levin综合征是一种罕见的疾病，其特点是反复发作的嗜睡，认知障碍和行为障碍，如食欲过盛和hypersexuality.Methods：我们收集了详细的临床资料和血液样本的108例患者，79父母对，和108匹配的对照组。我们测量的生物标志物和人类白细胞抗原基因DR和DQ分型。结果：新的易感因素，确定包括出生和发育问题（比值比，6.5）增加。犹太人遗产被过度代表，并确定了五个多元化的家庭。人类白细胞抗原分型无异常。78%的患者为男性（平均发病年龄15.7 ± 6.0岁），平均发作19次，每次13天，14年中失能8个月。男性和性欲亢进患者的病程较长，发病年龄在20岁以后。在发作期间，所有患者都有嗜睡、认知障碍和现实错乱; 66%的患者有巨噬症; 53%的患者报告性欲亢进（主要是男性）; 53%的患者报告抑郁情绪（主要是女性）。患者在睡眠、情绪和饮食态度方面与对照组非常相似，但体重指数增加。我们发现金刚烷胺和情绪稳定剂的边际疗效，但没有发现增加家族史的neuropsychiatric disorders.Interpretation：跨研究的临床和人口统计学特征的相似性强烈表明，Kleine-Levin综合征是一个真正的疾病实体。家族聚集性和犹太人群中患病率的增加支持了一个主要遗传易感因素的作用。考虑到现有治疗的无效性，我们建议疾病管理应主要是支持和教育。
Objective: Kleine-Levin syndrome is a rare disorder characterized by relapsing-remitting episodes of hypersomnia, cognitive disturbances, and behavioral disturbances, such as hyperphagia and hypersexuality.Methods: We collected detailed clinical data and blood samples on 108 patients, 79 parent pairs, and 108 matched control subjects. We measured biological markers and typed human leukocyte antigen genes DR and DQ.Results: Novel predisposing factors were identified including increased birth and developmental problems (odds ratio, 6.5). Jewish heritage was overrepresented, and five multiplex families were identified. Human leukocyte antigen typing was unremarkable. Patients were 78% male (mean age at onset, 15.7 +/- 6.0 years), averaged 19 episodes of 13 days, and were incapacitated 8 months over 14 years. The disease course was longer in men, in patients with hypersexuality, and when onset was after age 20. During episodes, all patients had hypersomnia, cognitive impairment, and derealization; 66% had megaphagia; 53% reported hypersexuality (principally men); and 53% reported a depressed mood (predominantly women). Patients were remarkably similar to control subjects between episodes regarding sleep, mood, and eating attitude, but had increased body mass index. We found marginal efficacy for amantadine and mood stabilizers, but found no increased family history for neuropsychiatric disorders.Interpretation: The similarity of the clinical and demographic features across studies strongly suggests that Kleine-Levin syndrome is a genuine disease entity. Familial clustering and increased prevalence in the Jewish population support a role for a major genetic susceptibility factor. Considering the inefficacy of available treatments, we propose that disease management should primarily be supportive and educational.