摘要：
目的 分析总结8例家族性致死性失眠症(FFI)患者的临床特征、多导睡眠监测(PSG)、影像检查、基因分析及实验室检查的结果,以提高对该病的临床认识.方法 回顾性总结2009-2018年首都医科大学宣武医院神经内科收治的经过基因检查确诊的8例FFI患者的临床表现、神经心理学检查、脑脊液检查、PSG、头颅磁共振成像、单光子发射计算机断层扫描(SPECT)、1sF-氟代脱氧葡萄糖(FDG)-正电子发射断层摄影术(PET)、脑电图等资料.结果 8例FFI患者中,男3例,女5例,起病年龄(49.8±14.3)岁(19～64岁),病程8～18个月.所有8例患者基因检查均显示20号染色体朊蛋白基因(PRNP)出现D178N突变,129位氨基酸多态性为M/M型,其中5例患者有家族史.8例患者均有睡眠障碍以及与睡眠相关的不自主运动、呼吸困难、喉鸣;8例患者均出现快速进展性痴呆,并伴或不伴有精神症状、共济失调、锥体束及锥体外系损害;8例患者均有自主神经损害,表现为高血压、出汗、心动过速、不规则呼吸等症状.3例患者SPECT/18F-FDG-PET提示丘脑葡萄糖代谢减低.7例患者PSG提示总睡眠时间减少,睡眠-觉醒周期障碍,尤其是快速眼球运动睡眠期减少或缺失,并记录到呼吸困难、喉鸣及不自主运动.结论 FFI表现为睡眠障碍及睡眠相关的非自主运动、呼吸困难、喉鸣、快速进展性痴呆及自主神经损害,家族史、PSG和PET检查有助于FFI的诊断,PRNP基因序列的分析能明确FFI的诊断.%Objective To investigate the clinical features,polysomnography,imaging examination,genetic analysis and laboratory examination of eight patients with familial fatal insomnia (FFI).Methods The clinical data,neuropsychological examination,results of cerebrospinal fluid analysis,imaging examination and polysomnography of eight patients with FFI in Xuanwu Hospital,Capital Medical University from 2009 to 2018 were retrospectively analyzed and summarized.Results Among the eight FFI patients,there were 3 males and 5 females,the onset age being (49.8+14.3) years (19 to 64 years) and the course of disease being eight to 18 months.D178N mutation in the PRNP gene of chromosome 20 and 129 amino acid polymorphisms of M/M were found in genetic examination in all the eight patients,of which five patients had family history.All the patients had sleep disorders,sleep-related involuntary movement,sleep-related dyspnea,laryngeal stridor.All the patients showed rapid progressive dementia with or without symptoms or signs of psychosis,ataxia,pyramidal and extrapyramidal.All the eight patients had progressive sympathetic symptoms,including hypertension,sweating,tachycardia,irregular breathing,and dysarthria.Cerebrospinal fluid 14-3-3 protein was found positive in one patient,and negative in seven patients.Electroencephalograph showed diffuse slow wave and non periodic synchronous discharge.Single-photon emission computed tomography or 18F fluorodeoxyglucose positron emission tomography showed decreased thalamic glucose metabolism in three patients.Seven patients showed decreased total sleep time,sleep awakening cycle disorder,especially the reduction or loss of rapid eye movement,laryngeal stridor and involuntary movement in polysomnography.Conclusions FFI is characterized by sleep disorder,sleep-related involuntary movement,dyspnea,laryngosis,rapid progressive dementia and sympathetic symptoms.The family history,polysomnography and positron emission tomography are helpful for the diagnosis of FFI.PRNP gene detection can confirm the diagnosis of FFI.
