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

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