Creutzfeldt-Jakob disease and sheep brain a report from central and southern Italy

The places of origin of 7 out of 8 patients with CJD coincide with the distribution of sheep-rearing in central and southern Italy, confirming the suggested link between this disease and eating and-or handling sheep CNS tissue. Since 6 of the 8 cases were women, it seems more likely that the virus responsible for CJD enters the body through a break in the skin of the hands and forearms in the process of foodhandling rather than via the Digestive tract. This aspect should be borne in mind when investigating the problems of CJD transmission.     

Virus-like particles in brain tissue from two patients with Creutzfeldt-Jakob disease

Summary Particles resembling virions observed in brain biopsies of two patients with Creutzfeldt-Jakob disease were located almost exclusively in the cytoplasm of the astrocytes which were swollen and showed accumulations of glia fibres, sometimes the cell bodies of the astrocytes were destroyed.

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Zusammenfassung Virusähnliche Partikel wurden in Gehirnbiopsien von zwei Patienten mit Creutzfeldt-Jakobscher Krankheit beobachtet. Diese Partikel fanden sich fast ausschließlich im Cytoplasma von Astrocyten, die eine Konzentration von Gliafilamenten, Schwellung oder sogar Desintegration zeigten.

     

Sensory features of variant Creutzfeldt-Jakob disease

Objective: Sensory symptoms are a prominent feature of variant Creutzfeldt-Jakob disease (vCJD), occurring at an early stage of the illness. They are persistent and can be troublesome. Here, they are described in detail and a possible anatomical basis is discussed. Methods: The first 50 cases of vCJD confirmed by the National CJD Surveillance Unit (NCJDSU) were reviewed. Where possible the patients and their relatives were interviewed and case notes were examined. The presence and nature of sensory symptoms and signs were noted. Results of investigation and types of treatment offered were also reviewed. Results: Of 50 definite cases, 64 % had persistent sensory symptoms, 16 % had no sensory symptoms and 18 % were uncertain. In 2 % there was insufficient information. Of the 32 with definite symptoms, 31 % were symptomatic from the onset of the illness. The symptoms were varied and some patients complained of more than one type of symptom. Limb pain was described in 63 % cases. This was the most common symptom and was often non-specific and poorly localised, usually occurring in the lower limbs. Other symptoms included cold feelings (25 % patients), dysaesthesia (28 % patients), paraesthesia (31 % patients) and numbness (25 % patients). The symptoms were lateralised in 31 % of patients. Conclusions: Sensory symptoms are a prominent feature of vCJD, occurring in nearly two thirds of cases. They may help distinguish variant from sporadic CJD. They are likely to be of thalamic origin but the recognised MRI changes in vCJD do not correlate with the presence or absence of sensory symptoms. Neuropathological changes in the thalamus, however, show marked astrocytosis and neuronal loss. Received: 16 July 2001, Received in revised form: 24 October 2001, Accepted: 7 November 2001     

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.     

Two familial cases of Creutzfeldt-Jakob disease in Italy

Two familial Italian cases of Creutzfeldt-Jakob disease are reported. Clinical picture and life history are presented and compared: 1) with the findings in familial cases reported in other countries, 2) with the findings (age at onset, disease duration) in sporadic Italian cases.

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Sommario Sono presentati due casi famigliari italiani di malattia di Creutzfeldt-Jakob. Sono descritti il quadro clinico e il decorso e viene fatta una comparazione coi dati riportati su casi famigliari in altre nazioni e coi dati concernenti casi italiani sporadici.

     

Kuru-plaques in a case of Creutzfeldt-Jakob disease

Summary Numerous periodic-acid-Schiff positive plaques occurred in the cerebellum of a patient diagnosed as having Creutzfeldt-Jakob disease. Microscopic and submicroscopic structures of the plaques were identical with those described in Kuru. This is an additional link between these two neurological diseases in which the clinical, histopathological, and virological features are in many respects similar.Supported in part by U.S. NIH Institutional Research Grant (West Virginia University.)     

Alpers' disease — A variant of Creutzfeldt-Jakob disease and subacute spongiform encephalopathy?

Summary A case of Alpers' disease is described and the findings analysed in relation to subacute spongiform encephalopathy and Creutzfeldt-Jakob disease, suggest that these three diseases have enough in common to indicate that they represent the same reaction of the brain at different ages and are all possibly based on an anoxic or vascular pathogenesis.

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Zusammenfassung Ein Fall von Alpersscher Krankheit wird beschrieben und die Befunde in ihrer Beziehung zur subakuten spongiformen Encephalopathie und zur Jakob-Creutzfeldtschen Krankheit erörtert. Die Annahme wird vorgebracht, daß diese drei Krankheitsbilder durch einige Gemeinsamkeiten auf eine und dieselbe Reaktionsform des Gehirns, die mit dem Alter differiert, hinweisen und möglicherweise eine anoxische oder vasculäre Pathogenese besitzen.

     

Creutzfeldt-Jakob disease in Hong Kong A case report

This is a report of a Chinese male, aged 67, who had been ill for 6 months and who was admitted with left hemiparesis and dementia. The diagnosis of Creutzfeldt-Jakob disease (CJD) was confirmed by serial electroencephalographic (EEG), computed tomographic (CT) and neuropathological studies. This is the first formal report of CJD occurring in Hong Kong.     

Electron microsocopy of brain amyloid plaques from a patient with new variant Creutzfeldt-Jakob disease

Cerebral cortex biopsy from a patient with new variant Creutzfeldt-Jakob disease (nvCJD) has been examined at the electron microscope level. Spongiform changes corresponded mostly to distended neurites scattered in the neuropil or surrounding amyloid plaques. These latter exhibited heterogeneous submicroscopic morphology including variable amount of loosely interwoven amyloid fibrils admixed in a cellular-rich environment constituted essentially by abnormal neuronal processes. By immunoelectron microscopy, fibrils and some membrane structures reacted with anti-prion protein (PrP) antibodies. One striking aspect was the presence of many small dystrophic neurites without paired helical filaments. Moreover, amyloid fibrils showed unexpected intimate association with abnormal membranes, suggesting a relationship between PrP fibrillogenesis and membrane alteration. These ultrastructural findings provide an additional criterion to distinguish nvCJD- from sporadic CJD-type plaques and reinforce the hypothesis that nvCJD brain is infected by a distinctive strain of the transmissible agent encephalopathy. Received: 7 June 1999 / Accepted: 21 September 1999     

散发性CJD患者新的潜在标志物H-FABP的检测

目的通过检测散发性CJD患者血清和脑脊液中心脏型脂肪酸结合蛋白(H—FABP)的含量,来探索 H—FABP对于CJD生前诊断的意义。方法应用ELISA方法对我科1998年～2005年收集的散发性CJD患者血清 13例和脑脊液17例进行H—FABP检测,同时设立正常对照组,进行统计学分析。结果散发性CJD患者血清及脑脊液H—FABP浓度均较正常对照组高,具有统计学意义。结论作为散发性CJD新的潜在生物学标志物H—FABP 的检测结果有助于该病的生前诊断,进行血液筛查也能降低CJD通过输血进行医源性传播的危险性。     

Wernicke encephalopathy and Creutzfeldt-Jakob disease

We assessed the prevalence of Wernicke encephalopathy (WE) in all 657 cases suspected of Creutzfeldt-Jakob (CJD) referred from 2001 to 2006 to the French Neuropathology Network of CJD. Clinical, biological and imaging data were reviewed when the diagnosis of WE was made at autopsy. No CJD was found in five cases suspected of sporadic CJD. In these five cases, myoclonus had been observed in four, CSF 14-3-3 protein in two. In 14 other cases, WE was combined with CJD, 13 of which were sporadic. These belonged mainly to the molecular variants of sporadic CJD associated with a long duration of disease. This stresses the necessity of remaining alert to the diagnosis of WE when CJD is suspected.     

Unusual findings in Creutzfeldt-Jakob disease. Case report

We present a definite case of Creutzfeldt-Jakob disease (CJD) with visual evoked response (VER) and CSF oligoclonal band abnormalities and discuss the neurobiological significance and diagnostic value of these findings.

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Sommario Il significato neurobiologico e il valore per la diagnosi differenziale delle alterazioni dei PEV e della presenza di bande oligoclonali nel CSF nella CJD viene discusso in un caso.

     

Creutzfeldt-Jakob disease with plaques and paired helical filaments

A 32-year-old man with rapidly progressive dementia, pyramidal signs, myoclonic jerks and dystonic movements died following brain biopsy. neuropathological examination revealed minimal neuronal loss accompanied by mild spongiform change and astrocytic reaction. Numerous plaques and neurofibrillary tangles composed of paired helical filaments dominated the ultrastructural picture. This patient had features of both Creutzfeldt-Jakob disease and Alzheimer's disease, providing additional support for the existence of an overlap between these disorders.     

Creutzfeldt-Jakob病的临床和影像学特点

目的探讨Creutzfeldt-Jakob病(CJD)的临床及影像学特征。方法回顾性分析29例CJD患者的临床资料。结果本组有12例CJD患者以快速进展性痴呆起病;典型的临床表现为进行性痴呆(100%)、共济失调(93.1%)、肌阵挛(89.6%)。EEG均异常,出现典型三相波17例、不典型三相波8例。头颅MRI表现双侧皮质高信号或基底节区T2WI对称性高信号15例,单侧皮质高信号6例,单侧基底节区高信号4例;20例行MR弥散加权成像(DWI)扫描,双侧皮质或基底节区出现高信号14例,一侧皮质或基底节区高信号各3例。14例双侧DWI高信号的患者均出现EEG典型三相波。3例行脑脊液14-3-3蛋白检查,2例阳性。结论 CJD患者多以快速进展性认知功能障碍起病,典型的临床表现为痴呆、共济失调、肌阵挛;EEG、DWI、CSF 14-3-3检测是诊断CJD的重要检查手段;DWI双侧皮质及基底节高信号可能与EEG出现三相波有关。     

Creutzfeldt-Jakob disease: A histochemical study with microdensitometric assay of some enzymes

Summary A variety of histochemical reactions were studied in a case of Creutzfeldt-Jakob disease and these were compared with normal brain. Several enzymes were assessed quantitatively using microdensitometric techniques. Neurones showed a loss of both oxidative and lysosomal enzymes. There was a raised activity in adjacent reactive glial cells. Affected cells also showed accumulation of lipofuscin pigment and loss of cytoplasmic RNA and nuclear DNA.     

Clusterin solubility and aggregation in Creutzfeldt-Jakob disease

Prion protein (PrP^C) is a glycolipid-anchored cell membrane syaloglycoprotein that localizes in presynaptic membranes. PrP has the property of aggregating into amyloid fibrils and being deposited in the brains in cases with transmissible encephalopathies (TSEs), when PrP^C is converted into abnormal protease-resistant PrP (PrP^RES). Clusterin is a heterodimeric glycoprotein, the expression of which is enhanced in astrocytes in association with punctate-type PrP^RES deposits during TSE progression. In addition, clusterin co-localizes in PrP^RES plaques in several human TSEs, including Creutzfeldt-Jakob disease (CJD). Clusterin is up-regulated in the cerebral cortex and cerebellum in CJD as revealed by DNA micro-array technology. Clusterin expression was examined in seven sporadic cases of CJD (codon 129 genotype, PrP type: 4 MM1, 1 MV1, 1 MV2, 1 VV2) and three age-matched controls by immunohistochemistry, Western blotting and solubility. In addition to small punctate clusterin deposition in the neuropil, single- and double-labeling immunohistochemistry disclosed clusterin localization in PrP^RES plaques, which predominated in the cerebellum of cases MV1, MV2 and VV2. Moreover, clusterin in plaques, but not punctate clusterin deposits, was resistant to protease digestion, as revealed in tissue sections pre-incubated with proteinase K. Clusterin in CJD, but not clusterin in control brains, was partially resistant to protease digestion in Western blots of total brain homogenates immunostained with anti-clusterin antibodies, which were processed in parallel with Western blots to PrP, without and with pre-incubation with proteinase K. Protein aggregation was analyzed in brain homogenates subjected to several solvents. PrP was recovered in the deoxycholate fraction in control and CJD cases, but in the SDS fraction only in CJD, thus indicating differences in PrP solubility between CJD and controls. Clusterin was recovered in the cytosolic, deoxycholate and SDS fraction in both CJD and control cases, but only clusterin from CJD was recovered in the urea-soluble fraction and, especially, in the remaining pellet. These findings demonstrate the capacity of clusterin to form aggregates and interact with PrP^RES aggregates. The implications of this property are not known, but it can be suggested that clusterin participates in PrP clustering and sequestration, thus modifying PrP toxicity in CJD.     

遗传性CJD一家系随访分析

目的随访一个遗传性朊蛋白病的家系,对全部家系成员进行朊蛋白基因(PRNP)突变的筛查,探讨患病者的表型和突变发生率。方法研究对象包括28例家系成员和310例健康对照。对研究对象的PRNP基因的开放阅读框架进行PCR扩增,产物直接测序,异常者重复测序,并与对照组对比。收集新发病例的影像和神经电生理资料。结果共发现15例G114V基因突变者,其中3例发病,12例为携带者。1例新发病的患者表现为进行性痴呆、肌阵挛、帕金森综合征,头颅MRI示左侧颞叶轻度萎缩,脑电图有典型的周期性放电。结论本家系为常染色体显性遗传的家族性CJD,新发病例的出现进一步明确了这一表型诊断,部分携带者不发病提示存在不完全外显。     

Pediatric Creutzfeldt-Jakob disease: probable transmission by a dural graft

A 10-year-old boy underwent a posterior fossa craniectomy for removal of a grade 2 cerebellar astrocytoma. Dural closure was achieved by the placement of a dural graft. Eight years later the patient developed dementia and myoclonus. Electroencephalography demonstrated generalized slow activity that evolved into a pattern of periodic tripahsic waves. Computed tomography scan and magnetic resonance imaging were unremarkable. Brain biopsy confirmed spongiform encephalopathy of the Creutzfeldt-Jakob type. In the light of previous reports of four similar occurrences, and of our own experience with two further cases of this disease, we believe that the cadaveric dura was the source of transmission of Creutzfeld-Jakob disease in our patient. The authors remark the importance of the awareness of this late complication of dural substitutes, both for the diagnosis of possible future cases and for taking preventive measures to stop the spread of the disease.     

Japanese Creutzfeldt-Jakob disease patients exhibiting high incidence of the E200K PRNP mutation and located in the basin of a river

Abstract

Seven cases with Creutzfeldt-jakob disease (CJD) located in the basin of the Fuji river (Fuji area) in japan were examined genetically and clinicopathologically. The onset of the disease was between 7989 and 1995. All cases Were from different families, although 3.cases were family members of previously reported CJD patients. They had clinical and,or neuropathological features, corresponding to suba.cute spongiform encephalopathy. Five of the 7 cases, including the 3 familial cases, had the E200K mutation in the gene encoding prion protein (PRNP). It is suggested that there is a small cluster of CJD patients with a founder effect of the E200K mutation in the Fuji area, because the incidence of CJD with the E200K mutation appears to be much higher in this area than other areas in japan. The disease penetrance of the 5 cases with the E200K mutation seems to be low, and they may have an age-related incidence in the Fuji area. These findings support the hypothesis that the phenotypes of CJD patients with the PRNP mutations are linked to the position of the mutation, but not related to ethnic or environmental factors. [Neural Res 1998; 20: 684-688]     

中国与奥地利Creutzfeldt-Jakob病的比较研究

目的 为更准确认识中国人Creutzfeldt-Jakob病（CJD）特殊性，比较中国和奥地利两国CJD在临床、病理等方面异同点。方法 对中国人CJD24例，奥地利人CJD79例，通过组织病理、免疫组化，实验动物传递、临床类型、病程经过等多方面进行比较。结果 （1）两国CJD报道例数有逐年增多趋势；（2）奥地利人绝大多数为剖检证实，中国人多为脑活检确定；（3）异常PrP沉积形式分突触型、空泡周围型和斑块型三种，奥地利人分别为71％、38％和10％；中国人分别为92％、8％和0％；（4）奥地利人突触型多在灰质密集分布，而中国人则为松散分布；（5）两国均发现年轻人和中年人发生的散发性CJD，但均无新变异型CJD。结论 两国CJD确实存在若干异同处，认清此点，对早期发现CJD，减少医源性传播有积极意义。