Abstract: Background　Sporadic Creutzfeldt-Jakob disease（sCJD）is a rare disease characterized by various clinical manifestations in the early stage，which is difficult to diagnose，requiring the assistance of an auxiliary examination.Objective　To analyze the clinical features and auxiliary examinations of 17 patients with clinically possible or probable sCJD，providing implications for early diagnosis of sCJD.Methods　By searching the records of patients with a discharge diagnosis of clinically possible or probable sCJD in Department of Medical Records，the Second Hospital of Hebei Medical University from November 2014 to August 2018，we collected their general information（gender，age，ethnic group，discharge diagnosis，first symptoms and major clinical manifestations），auxiliary examinations 〔brain MRI，EEG，CSF 14-3-3 protein，serum PRNP gene，autoimmune related antibodies of rapidly progressive dementia in serum and cerebrospinal fluid（ antibodies related to non-para-tumor autoimmune encephalitis，antibodies associated with para-tumor autoimmune encephalitis）〕.And by a telephone-based follow-up survey，we collected the data about morality and total duration of course.Results　Seventeen patients were enrolled，with an average age of（61.8±6.2）years，all of them were Han nationality.Sixteen of them were diagnosed with probable sCJD（94.1%）and other 1 with possible sCJD（5.9%）.The first symptoms mainly were memory decline（41.2%），dizziness（29.4%）and psychobehavioral abnormalities（17.6%）.The main clinical manifestations were cognitive decline（82.4%）and conical/extrapyramidal impairment（47.1%）.Diffusion-weighted imaging（DWI）of the brain performed in 16 cases showed that patients showed abnormally high signal intensity in cortex and/or basal ganglia，and correspondingly low signal intensity in apparent diffusion coefficient（ADC）.At least 2 lobes in the cortex showed abnormal high signals of gyrus along the surface of the brain，presenting "lace sign" or "ribbon sign".Basal ganglia included single/bilateral caudate nucleus，putamina，etc showed abnormal high signals in DWI.1 patient was examined by magnetic resonance spectroscopy（MRS），which revealed decreased peak of NAA.EEG was performed in 16 patients，the result includes 15 with slow basic rhythm，4 with PSWCs，5 with triphasic wave，and 4 with aperiodic epileptic discharge in the background with slow basic rhythm.CSF 14-3-3 protein test was performed in 8 patients，and 3 were positive.PRNP examination was performed in 8 patients，all showed：（1）no mutation in the sequence compared with the standard sequence（standard sequence number NCBI：NM-183079.1）；（2）polymorphism of amino acids at position 129 was M/M type；（3）amino acid polymorphism at position 219 was E/E type.Eleven patients were negative in serum and CSF non-para-tumor autoimmune encephalitis antibody tests.Nine patients were negative in serum and CSF para-tumor related antibodies test.All 17 patients were followed up by telephone，and 11 of them had died at the time of follow-up，with a total course of disease ranging from 1.5 to 16.0 months and an average of（7.4±4.7）months.The 1-year mortality rate was 81.8%（9/11）.Telephone contact failed in 2 patients.Family members of 2 patients refused to be followed up.The family members of one patient did not cooperate with the follow-up，and the patient died，the time of death was unknown，but the total course of disease was less than 14.0 months.One patient survived until 2019-02-01，the course of disease was 14 months.Among the 11 patients who died，9 patients developed into akinetic mutism，and 2 died due to bedsore infection.Brain DWI examination was performed in 10 cases（7 had abnormal signals in basal ganglia and cortex and the median course of the disease was 11.0 months，3 had abnormally high signal only in the cerebral cortex and the median course of disease was 4.0 months）.Conclusion　sCJD is a rapidly progressive and fatal neurodegenerative disease caused by prion protein infection.When the clinical manifestations are memory loss，visual abnormalities，etc，EEG，brain MRI，CSF 14-3-3 protein，RT-QuIC examination should be performed to clarify the clinical diagnosis.The disease progression may be faster when the isolated cortex is involved showed by the brain MRI and 14-3-3 protein is positive.The presence of aperiodic epileptiform discharges，characteristic triphasic waves，and PSWCs in EEG should be closely monitored for disease progression.

Key words: Creutzfeldt-Jakob syndrome, Creutzfeldt-Jakob disease, Sporadic, 14-3-3 protein, Prion protein, Triphasic waves

摘要： 背景　散发性克雅病（sCJD）临床罕见，早期临床表现多变，临床诊断困难，需要结合辅助检查进一步明确。目的　分析17例临床可能或很可能sCJD患者的临床特点及辅助检查结果，为sCJD早期临床诊断提供参考。方法　检索河北医科大学第二医院病案室2014年11月—2018年8月出院诊断为临床可能或很可能sCJD患者的住院病历。收集患者一般资料（性别、年龄、民族、出院诊断、首发症状、主要临床表现）、辅助检查〔颅脑MRI、脑电图（EEG）、脑脊液14-3-3蛋白、血清朊蛋白基因（PRNP）、自身免疫性相关的快速进展性痴呆的抗体检查（血清及脑脊液非副肿瘤自身免疫性脑炎相关抗体检查、副肿瘤相关抗体检查）〕结果。对患者进行电话随访，记录患者死亡情况、总病程。结果　共纳入17例患者，平均年龄（61.8±6.2）岁，均为汉族；出院诊断为很可能sCJD 16例（94.1%），可能sCJD 1例（5.9%）；首发症状主要为记忆力下降（41.2%）、头晕（29.4%）、精神行为异常（17.6%）；主要临床表现为认知下降（82.4%）、锥体束/锥体外系损害（47.1%）。16例患者颅脑弥散加权成像（DWI）均出现脑皮质和/或基底核异常高信号，相应表观扩散系数（ADC）低信号。皮质至少2处脑叶沿脑表面脑回状异常高信号，呈“花边征”或“绸带征”，基底核包括单/双侧尾状核、壳核等。1例患者行磁共振波谱成像（MRS）检查，影像学表现为N-乙酰天冬氨酸（NAA）峰降低。16例患者行EEG检查，其中基本节律减慢15例，周期性尖慢复合波（PSWCs） 4例，三相波5例，基本节律减慢背景上的非周期性的癫痫样异常放电4例。8例患者行脑脊液14-3-3蛋白检查，阳性3例。8例患者行PRNP检查，均为：（1）与标准序列比对，序列未出现突变（标准序列号NCBI：NM-183079.1）；（2）129位氨基酸多态性为M/M型；（3）219位氨基酸多态性为E/E型。11例患者行血清及脑脊液非副肿瘤自身免疫性脑炎相关抗体检查，均为阴性。9例患者行血清及脑脊液副肿瘤相关抗体检查，均为阴性。17例患者全部进行电话随访，其中11例患者电话随访时已经死亡，总病程1.5~16.0个月、平均（7.4±4.7）个月，1年内死亡率为81.8%（9/11）；2例患者电话空号；2例患者家属拒绝随访；1例患者家属不配合随访，患者已死亡，死亡时间不详，但其总病程<14个月；1例患者仍存活，至2019-02-01病程已达14.0个月。11例死亡患者中，发展至无动性缄默状态9例，因压疮感染而死亡2例；10例行颅脑DWI检查（其中7例患者基底核及皮质均有异常信号，总病程中位数为11.0个月；3例患者仅脑皮质有异常高信号，总病程中位数为4.0个月）。结论　sCJD是由朊蛋白感染的快速进展的、致命的神经变性病。当临床表现为记忆力下降、视觉异常等时，应行颅脑MRI、EEG、脑脊液14-3-3蛋白、实时震动诱导转换（RT-QuIC）检查明确临床诊断；出现颅脑MRI孤立皮质受累、14-3-3蛋白阳性时病情进展较快；出现EEG非周期性的癫痫样异常放电、特征性的三相波及PSWCs时，应密切关注患者疾病进展。

关键词: 克-亚综合征, 克雅病, 散发性, 14-3-3蛋白, 朊蛋白, 三相波