Creutzfeldt-Jakob病与路易体痴呆脑电图表现的研究进展

社会老龄化加速使神经系统变性疾病成为神经病学一个备受关注的领域。EEG作为一项无创、廉价、可重复的检查手段,在神经系统变性疾病中已有广泛应用。目前已有多种特征性EEG被纳入相应疾病的诊断标准。本文从临床角度对Creutzfeldt-Jakob病(CJD)及路易体痴呆(DLB)的EEG表现、产生机制、鉴别诊断及临床应用作以总结,以期对诊断及鉴别诊断起提示作用。     

Spatial distribution of abnormal EEG activity in Creutzfeldt-Jakob disease

ObjectivesElectroencephalogram (EEG) pattern in Creutzfeldt-Jakob disease (CJD) is characterized by diffuse abnormal activity, although lateralization to one hemisphere has been described in the first stages of the disease. This study aimed to determine whether abnormal EEG activity predominantly occurs in anterior versus posterior brain regions.MethodsAs part of a prospective study, the demographics, clinical features and MRI findings of genetic E200K CJD patients were collected. EEG was performed and the recordings reviewed for the typical periodic sharp wave complex (PSWC) and non-specific slow activity. Data were analyzed using the qEEG tool, and the activity in anterior and posterior regions of the brain compared.ResultsEleven genetic E200K CJD patients were included in the study (67% women). The average age was 59.1 ± 8.4 SD years and the average disease duration was 2.4 ± 2.1 months. EEG showed the classic PSWC pattern in 5/11 (45%) of the patients, and slow activity was seen in 9/11 (82%). EEG was normal in 2 patients. PSWC activity was diffuse in 2/5 patients and unilateral in 3/5 patients; slow activity was diffuse in 9 patients. Quantitative analysis of PSWC and slow activity showed no significant difference between anterior and posterior distribution.ConclusionThe abnormal EEG activity in CJD is diffuse with no clear spatial predominance in anterior or posterior brain regions.     

散发性Creutzfeldt-Jakob病30例临床分析

目的探讨散发性Creutzfeldt-Jakob病(sCJD)的临床、脑电图(EEG)及影像学特征。方法回顾性分析30例sCJD患者的临床资料。结果本组急性起病6例,亚急性起病18例,在发病1～3个月出现意识障碍、肌阵挛、去皮质强直状态;慢性起病6例,发病后1～2年出现上述典型症状。本组患者EEG均异常,早期表现广泛持续性慢波,中晚期出现典型三相波18例、不典型三相波8例。本组MRI表现双侧基底节区T2WI对称性高信号10例,右侧豆状核高信号1例;17例行MR弥散加权成像(DWI)扫描,均出现一侧或两侧额顶叶和/或枕叶皮质高信号,其中8例合并双侧基底节区对称性高信号。结论sCJD以亚急性起病多见,早期头颅DWI即可出现特征性额顶叶和/或基底节区高信号,为早期临床诊断提供依据;中晚期均出现意识障碍、肌阵挛、去皮质状态,EEG特征为三相波。     

Creutzfeldt-Jakob病磁共振弥散加权像与临床表现及脑电图一致性的研究

目的探讨散发性Creutzfeldt-Jakob病(CJD)早期、准确诊断的方法,评价磁共振弥散加权像(DWI)在CJD诊断中的地位。方法回顾性比较13例散发性CJD患者DWI异常信号与临床表现及脑电图三相波(PSD)的一致性。结果DWI异常信号与临床表现及脑电图PSD有较高的一致性,并且较临床症状和体征以及PSD表现更早,更敏感;DWI异常信号随病程不断变化,最先表现在大脑皮层区,而后表现在底节区,且底节区异常信号持续时间最长;DWI异常高信号对CJD诊断特异性为81.3%,敏感性为100%,但样本较小。结论临床可疑的CJD患者,头颅DWI检查完全可以作为早期、无创性、准确诊断的重要方法。     

Neurochemical changes in creutzfeldt-jakob disease

Summary A biochemical study of a case affected by Creutzfeldt-Jakob disease is reported. Changes were found in soluble and insoluble proteins, glycoproteins and mucopolysaccharides and in total lipids, glycolipids, phospholipids and gangliosides. Also CNPase, choline acetyltransferase, 5-nucleotidase and several glycosidases have an altered activity. All these data give a complete neurochemical pattern of the changes underlying the morphological and functional alterations in this disease.

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Zusammenfassung Es wurde ein Fall von Creutzfeldt-Jakob-Krankheit biochemisch untersucht. Normabweichungen wurden in den löslichen und unlöslichen Proteinen, Glycoproteinen und Mucopolysaccharide sowie in bezug auf die Gesamtlipide, Glycolipide, Phospholipide und Ganglioside gefunden. Auch CNPase, Cholin-acetyltransferase, 5-Nucleotidase und mehrere Glycosidasen zeigen abnorme Aktivität. Die hier dargelegten Befunde weisen auf die neurochemischen Aspekte, welche den morphologischen und funktionalen Normabweichungen bei dieser Krankheit zugrunde liegen.

     

Serial computed tomographic and electroencephalographic studies in Creutzfeldt-Jakob disease

The serial changes in computed tomography (CT) as correlated with the clinical and electroencephalographic findings were evaluated in 3 patients with Creutzfeldt-Jakob disease. The disease was subsequently confirmed histologically in 2. CT revealed that brain atrophy began in an early clinical stage and was prominent even before the state of akinetic mutism. Periodic synchronous discharges (PSDs) were observed either before or simultaneous with the observation of myoclonus. With progressive brain atrophy, the frequency of PSDs and the degree of myoclonus both decreased and disappeared 8 to 15 months after the onset of disease.     

Unusual EEG findings in a case of Creutzfeldt-Jakob disease

Summary A case is reported of histopathologically verified Creutzfeldt-Jakob disease of long duration (more than 3 years) with some clinical peculiarities. The prominent peculiarity was a nearly normal EEG during repeated examinations, even in the terminal stage.     

磁共振弥散加权对克-雅氏病早期诊断的意义

目的探讨克-雅氏病(Creutzfeldt-Jakob disease,CJD)早期的磁共振弥散加权成像(DWI)表现。方法回顾性分析和总结3例CJD患者的临床症状及体征、影像学、脑电图和脑脊液中14-3-3蛋白的改变等资料。结果 3例患者脑部MRI均表现为皮质不同程度的DWI"缎带样"高信号,脑电图均出现周期性尖慢波或三相波,脑脊液14-3-3蛋白2例(+),1例(-)。结论对于绝大部分CJD患者,无论脑电图和脑脊液中14-3-3蛋白是否改变,DWI即可先于前两者出现异常改变,对于临床上出现早期相应症状及体征的患者,若DWI有此特征性改变,应高度疑诊CJD,故应考虑将DWI的异常改变纳入CJD的临床诊断标准中。     

Creutzfeldt-Jakob病43例患者的临床分析

目的分析43例临床可能或很可能克雅氏病(CJD)患者的临床特征,为CJD早期诊断提供一些参考。方法搜集2013年1月至2016年1月以"可疑CJD"诊断在首都医科大学宣武医院住院的患者,对其临床特点及实验室资料进行分析。结果 CJD通常在60岁左右发病,平均病程5.70±5.08个月;首发症状多变,以迅速进展性痴呆为主。典型临床表现有6种:迅速进展的痴呆、运动系统损害(锥体束、锥体外系及小脑症状)、肌阵挛、无动性缄默、睡眠障碍和视力障碍。结论 CJD的早期诊断应重视其临床特征,当一个患者具有典型特征中的两项或以上表现时,即使14-3-3蛋白、脑电图(EEG)、磁共振(MRI)均不典型,也要高度警惕CJD,定期复查,以免漏诊。     

The first two patients with dura mater associated Creutzfeldt-Jakob disease in the Netherlands

Creutzfeldt-Jakob disease (CJD) can be transmitted through human growth hormone or gonadotrophin administration, dura mater or cornea transplantation, depth EEG monitoring and the use of contaminated neurosurgical instruments. We describe the first two dura mater associated CJD cases in the Netherlands. Ten and fourteen years before the onset of symptoms both patients received a Lyodura implantation. Findings are discussed in light of the growing epidemic of CJD among dura mater recipients. Received: 5 December 2000, Received in revised form: 5 March 2001, Accepted: 4 April 2001     

克-亚二氏病的周围神经损害

目的 探讨克-亚二氏病(CJD)肌电罔与临床的关系。方法 分析5例CJD患者，2例为病理诊断，3例为临床诊断，对5例患者进行肌电图检查，其中1例病人在病程的不同阶段进行肌电图观察，并将肌电图改变与临床症状和体征进行分析总结。结果 5例病人中，1例出现束颤电位，1例出现神经性受损，其余3例为阴性。结论 在散发的CJD中，周围神经系统的损害应看作是疾病的一部分。     

Spongiform-like changes in Alzheimer's disease

Summary The ultrastructural study of the cortex of four patients with sporadic or familial AD, of two agematched controls without dementia, and of one normal pressure hydrocephalus, revealed in all the cases in the neuropil only occasional vacuoles which had a morphology similar to those observed in CJD. The degree of spongiform-like changes was, however, far less prominent than in CJD and considered mild in all the cases examined. Moreover, curled fragments of membranes within the vacuoles were not observed. It is suggested that the mild vacuolization of the neuropil occasionally observed in cortical biopsies of AD is a non-specific finding and cannot be considered a neuropathologic link between AD and CJD.     

Early myoclonus and quasiperiodic EEG changes in non-familial Alzheimer's disease

Large numbers of neurofibrillary tangles and neuritic plaques were found in a cerebral biopsy from a 52-year-old woman suffering from subacute dementia with early myoclonus and quasiperiodic EEG changes. This case, which appeared to be an example of non-familial Alzheimer's disease, is commented in the context of possible relation of Alzheimer's disease to transmissible dementia. Read before meeting of the Italian EEG Society. Parma, Nov. 24, 1978.     

Unusual clinical course in a case of Creutzfeldt-Jakob disease

An unusual clinical course of Creutzfeldt-Jakob Disease (CJD) is described. After a rapid progression to coma, the patient has survived for 16 months to date. To our knowledge a terminal, preagonal stage of this duration in CJD has never been reported. Since Methisoprinol was administered, the drug may have had a beneficial effect on the duration of the disease.Two and half months after the submission of this paper, the patient died. Histological examination confirmed the clinical diagnosis of CJD.     

Descriptive epidemiology of Creutzfeldt-Jakob disease in Finland

In 1974-84 30 patients died with a diagnosis of Creutzfeldt-Jakob disease (CJD) in Finland. Sixteen of the patients were pathologically confirmed and 14 were probable cases; 6 were familial (20%). One further familial patient was alive at the end of 1984. The median age of the 30 patients at death was 59.5 years (range 46-73 years). The familial patients were significantly younger than sporadic cases (median and range 49.5 and 46-57 versus 61.5 and 51-73; P less than 0.01). Only 5 of the 24 sporadic patients were men (male to female ratio 1:3.8). The annual number of new cases as well as the death rate increased in the late 1970's (annual death rate 0.57 per million in 1974-84 and 0.91 in 1979-84). This probably reflects the growing awareness of CJD among neurologists, rather than a real increase of the incidence and death rate. Annual age-specific death rate per 1 million population in 1974-84 reached a peak value of 2.57 in the age group of 60-64 years. In sporadic CJD the age-specific death rate of women was higher than that of men in all age groups. A chronic medical condition, precedent or concomitant with CJD, was seen in 15 patients.     

EEG changes during long-term treatment with donepezil in Alzheimer's disease patients

Summary. In this pilot study, we examined the long-term treatment effect of donepezil on the quantitative EEG (qEEG) in 12 Alzheimer's disease patients. The qEEGs of the mean absolute and relative amplitudes of betal, alpha, theta and delta activities were obtained at baseline and during donepezil treatment. Comparisons of awake qEEG prior to and during treatment were performed using a 2-way analysis of variance (ANOVA) with repeated measures. In patients with mild dementia (n = 5), the qEEG analysis showed a significant reduction of the mean absolute theta activity (p = 0.05) by donepezil, particularly in frontal and temporo-parietal areas. In patients with moderate/severe dementia (n = 7), a significant decrease in the mean absolute beta 1 activity (p = 0.02), particularly in the frontal and occipital areas may be attributed to disease progression which was not counteracted by the long-term treatment. The differences in qEEG in patients with different stages of dementia under donepezil treatment may be related to different compensatory capacities due to structural and functional brain disturbances. Received January 27, 2001; accepted June 8, 2001     

S-100 protein concentration in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease

We evaluated S-100 levels in paired cerebrospinal fluid (CSF) and serum samples in a group of 135 patients referred to the German Creutzfeldt-Jakob disease (CJD) surveillance unit from June 1993 to May 1995. The patients were seen in a prospective case control study. The diagnosis of probable CJD during life was made in any patient presenting with rapidly progressive dementia of less than 2 years’ duration, typical periodic sharp wave complexes (PSWCs) in the EEG and at least two of the following findings: myoclonus, visual/or cerebellar symptoms, pyramidal and/or extrapyramidal signs and/or akinetic mutism. Patients presenting with the above clinical signs and symptoms but without PSWCs were classified as possible, while those with a dementia of a duration exceeding 2 years and without PSWCs were classified as other. S-100 was determined in paired CSF and serum samples by a commercially available enzyme-linked immunosorbent assay. In a group of 76 patients with definite and probable CJD, S-100 concentration (median 25 ng/ml, range 2–117) in CSF was significantly higher (P < 0.0001) than in 32 patients diagnosed as other (median 4 ng/ml, range 1–19). Serum levels of S-100 were below 0.5 ng/ml in all groups. At a cut-off of 8 ng/ml an optimum sensitivity of 84.2% with a specificity of 90.6% for the diagnosis of CJD by the determination of S-100 in CSF is obtained. S-100 levels exceeding 8 ng/ml in CSF support the diagnosis of CJD in any patient presenting with rapidly progressive dementia. Received: 20 February 1997 Received in revised form: 16 July 1997 Accepted: 1 August 1997     

The first case of new variant Creutzfeldt-Jakob disease in France: clinical data and neuropathological findings

Clinical data and autopsy findings in a case of new variant Creutzfeldt-Jakob disease (vCJD) are reported. This case, the first histologically confirmed case described outside the United Kingdom, very much resembles the cases described by Will et al. [(1996) Lancet 347:921-925] and Zeidler et al. [(1997) Lancet 350:903-908, 908-910]. Neuropathological studies failed to reveal any conspicuous clues that could be relevant for understanding the pathophysiology of the disease. For epidemiological surveillance, neuropathologists should scrutinize suspected cases keeping in mind the possibility of vCJD.     

The coexistence of Alzheimer's disease and Creutzfeldt-Jakob disease in a patient with dementia of long duration

Summary We report here a 75-year-old-male with a slowly progressive dementia of 5-year duration along with a rapid exacerbation of symptoms in the terminal 3 months. Neuropathological examinations revealed findings consistent with conspicuous Alzheimer's disease and mild Creutzfeldt-Jakob disease (CJD). The plaque amyloid was exclusively composed of -protein. The immunohistochemistry of prion protein using hydrolytic autoclaving pretreatment showed diffuse gray matter stainings in the sections of both the cerebral and cerebellar cortices. This method was thus considered useful in confirming the diagnosis of CJD for this case.     

Serial EEG findings in sporadic and iatrogenic Creutzfeldt-Jakob disease.

OBJECTIVE: To study temporal and spatial development of EEG patterns in sporadic and iatrogenic Creutzfeldt-Jakob disease patients. METHODS: Temporal and spatial development of EEG patterns in 4 patients with sporadic Creutzfeldt-Jakob disease and 2 patients with iatrogenic Creutzfeldt-Jakob disease due to implantation of contaminated brain depth electrodes were investigated. A total of 56 EEGs were analyzed, over time spans ranging from 1272 to 3 days prior to death. RESULTS: Frontal intermittent rhythmical delta activity (FIRDA) was seen at early timepoints in 4/6 patients and might represent an early EEG pattern that is associated, with human prion diseases. EEG patterns associated with CJD are sensitive to midazolam. Initial EEG changes were seen at the site of prion exposure in iatrogenic Creutzfeldt-Jakob disease patients, before they could be observed at distant sites, suggesting that prion disease was initiated at the site of prion exposure. CONCLUSIONS: Serial EEG recordings are a valuable tool not only in the early diagnosis of sporadic CJD, but also in the determination of prion exposure in iatrogenic Creutzfeldt-Jakob disease. SIGNIFICANCE: FIRDA occur at an early stage of CJD and are progressively replaced by the classical PSWC. The EEG patterns of CJD are sensitive to midazolam. The initial EEG changes in iatrogenic CJD are seen at the site of prion exposure.