Hereditary Creutzfeldt-Jakob disease caused by a mutation at codon 200

INTRODUCTION: A typical case of genetic Creutzfeldt-Jakob disease in a 39-year-old woman without remarkable familial history is described. CASE REPORT: Initial symptoms were disequilibrium, cerebellar syndrome and complex neurovisual complaints. EEG was pseudoperiodic. NSE and 14-3-3 protein levels were elevated in the CSF. MRI showed anomalies of the anterior parts of the putamen and the caudate nuclei on the MRI T2 FLAIR sequence, mainly on diffusion sequences. A quinacrine test did not yield any effect. Death eventually occurred 8 months after the first symptoms. CONCLUSION: Current data on genetic Creutzfeldt-Jakob disease are briefly reviewed.     

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.     

Wernicke's encephalopathy associated with chronic disulfiram intoxication

INTRODUCTION: We report the case of a patient with an unusual association of Wernicke encephalopathy and chronic disulfiram intoxication. CASE REPORT: A 41-year-old man presented with progressive frontal decline and akineto-rigid parkinsonism under chronic disulfiram therapy. He also developed acute confusion with ataxia, blepharospasm, and supranuclear ophthalmoplegia following a severe malnutrition due to refusal of food intake. Brain MRI revealed symmetrical and reversible hyperintense lesions on T2 and FLAIR in the posterior putaminal regions, dorso-medial thalamic and subthalamic nuclei, the periaqueducal gray matter, the cerebellar peduncles, and the pontine tegmentum. A slow partial clinical recovery with persistent frontal syndrome was observed after discontinuation of disulfiram and parenteral administration of thiamine. DISCUSSION: The symmetry and reversibility of the MRI lesions in the basal ganglia and brain stem were suggestive of a deficiency, a toxic or a metabolic neurological disease. The dorso-medial thalamo-subthalamic and brainstem localizations, as well as their occurrence in a state of malnutrition, were consistent with Wernicke encephalopathy. Moreover, chronic disulfiram intoxication might explain the frontal syndrome and the akineto-rigid parkinsonism, associated with MRI putaminal lesions. Similar MRI lesions have been described in the so-called "energy deprivation syndromes", which are toxic, genetic or nutritional disorders that disrupt enzymes involved in energy generating metabolic pathways such as glycolysis and pyruvate oxidation.     

Wernicke's encephalopathy mimicking variant Creutzfeldt-Jakob disease

A 45-year-old man from tropical Australia was admitted with subacute social withdrawal, cognitive deterioration, reduced awareness and eventual mutism. Variant Creutzfeldt-Jakob disease was considered on the basis of WHO case definition criteria including typical clinical features and MRI showing symmetrical hyperintensity in the pulvinar (posterior) nuclei of the thalami. However, tonsillar biopsy was negative. Wernicke's encephalopathy was established on the basis of low serum thiamine on admission and eventual clinical improvement on high-dose intravenous thiamine replacement, despite initial failure to respond to the standard dose of 100 mg daily intramuscularly.     

Primary hyperparathyroidism as a differential diagnosis of Creutzfeldt-Jakob disease

We report the case of a 79-years-old woman, hospitalized for a suspicion of Creutzfeldt-Jakob disease because of subacute dementia associated with gait disorder. Laboratory testing revealed elevated serum calcium at 3.51 mmol/l (N = 2.25-2.60 mmol/l) caused by a hyperparathyroidism. After symptomatic treatment of hypercalcemia by biphosphonate, cognitive functions as well as the gait disorder improved quickly. A double parathyroid adenoma was removed surgically. Primary hyperparathyroidism is a curable cause of a Creutzfeldt-Jakob like syndrome. Serum calcium should be checked in this clinical setting.     

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.

     

家族性Creutzfeldt-Jakob病

目的确定家族性Creutzfeldt—Jakob病（CJD）的临床特点并探讨其可能的发病机制。方法对一个CJD家系进行系谱调查,并采用蛋白捕获法进行脑脊液14-3—3蛋白定量;应用PCR方法,结合DNA测序技术,检测朊蛋白（PrP）基因类型。结果（1）两代4例的发病年龄早于散发性CJD,而且有早发的趋势;（2）先证者脑脊液14-3—3蛋白为125ng／ml,高出截点13．9。倍;（3）先证者PRNP第788碱基和789碱基之间插入1个碱基A,致使PRNP第231位点发生插入突变;（4）患者弟弟及其女儿未发现有PrP基因突变。结论先证者为PRNP第231位点插入突变致家族性CJD,其临床表型与散发性CJD无明显不同,但发病年龄早于散发性CJD,同一家系患者死于同一年龄段。     

Sporadic Creutzfeldt-Jakob disease mimicking variant Creutzfeldt-Jakob disease

BACKGROUND: The determination of the form of prion disease and early diagnosis are important for prognostic, public health, and epidemiologic reasons. OBJECTIVE: To describe a patient with sporadic Creutzfeldt-Jakob disease (sCJD) who had a clinical history and initial electroencephalogram and magnetic resonance imaging findings consistent with variant CJD (vCJD). RESULTS: Results of a repeated electroencephalogram were suggestive of sCJD, and a subsequent brain biopsy confirmed this diagnosis. CONCLUSIONS: This case cautions against relying solely on T2- and diffusion-weighted pulvinar hyperintensity and clinical features to differentiate between vCJD and sCJD, and further supports established diagnostic criteria for vCJD.     

Pseudoperiodic EEG heralding a cefepime-induced encephalopathy

Electroencephalography is a useful tool for the diagnosis and follow-up of toxic and metabolic encephalopathies. A pseudo-periodic pattern can indicate various brain pathologies and causes of mental confusion. Among these, cefepime encephalopathy should always be considered, particularly in cases of renal failure, because of the reversibility of the symptoms at drug withdrawal.     

Creutzfeldt-Jakob disease

Summary The neuropathological findings in 3 cases of Creutzfeldt-Jakob disease are described.The triad of morphological changes, i.e. neuronal loss, status spongiosus of the grey matter and proliferation and hypertrophy of fibrous astrocytes with or without microglial reaction, conforms to the typical pattern of pathology described in the literature. Degeneration of the cerebellum places these cases in the cortico-striato-cerebellar variant of the disease.The distribution of the lesions within cerebrum and cerebellum, with a more severe involvement of phylogenetically older portions, is unusual. In the cerebrum cortices belonging to the limbic system and the striatum were the most severely affected, whilst in the cerebellum the vermis and flocculo-nodular lobe bore the brunt of the pathological process. A similar distribution of the lesions is generally found in kuru.Further similarities with kuru are pointed out i.e. the occurrence of swollen, chromatolytic neurones predominantly within the infragranular layers of the cerebral cortex, of coarse intracytoplasmic vacuolation in many of the large striatal nerve cells and of kuru plaques within the cerebellum. Similarities and differences between the two diseases are discussed.

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Zusammenfassung Die neuropathologischen Befunde von 3 Fällen von Creutzfeldt-Jakobscher Krankheit werden beschrieben.Die Trias der morphologischen Veränderungen — Nervenzelluntergang, Status spongiosus in der grauen Substanz, Proliferation und Hypertrophie faserbildender Astrocyten mit und ohne Mikrogliareaktion — entspricht dem typischen Muster der pathologischen Veränderungen in anderen Fällen der Literatur. Ihre Kleinhirnbeteiligung reiht die Fälle in die cortico-striato-cerebelläre Variante der Krankheit ein.Ungewöhnlich ist die Verteilung der Veränderungen im Großhirn und Kleinhirn mit der Bevorzugung phylogenetisch älterer Anteile. Am Großhirn waren die Rindenabschnitte des limbischen Systems und das Striatum am stärksten befallen; am Kleinhirn hat der pathologische Prozeß hauptsächlich den Vermis und Lobus flocculo-nodularis angegriffen. Eine ähnliche Anordnung der Veränderungen findet sich bei der Kuru-Krankheit.Weitere Ähnlichkeiten mit Kuru werden hervorgehoben, wie das Vorkommen von geschwollenen chromatolytischen Nervenzellen, besonders in den infragranulären Großhirnrindenschichten, von groben intracytoplasmatischen Vacuolen in vielen großen Striatumneuronen und von Kuru-Plaques im Kleinhirn. Ähnlichkeiten und Unterschiede der beiden Krankheitsbilder werden diskutiert.

     

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。     

Heidenhain's variant of Creutzfeldt-Jakob's disease

INTRODUCTION: Creutzfeldt-Jakob's disease has various anatomoclinical presentations including a rare form with preponderant visual signs described by Heidenhain. In this form, the visual symptoms may be isolated for a few weeks, leading to multiple ophthalmological examinations. OBSERVATION: We report the case of a 75-year-old woman who developed isolated visual disorders which rapidly increased over a period of two months. Addition of neurological symptoms, abnormalities of EEG and positivity of 14-3-3 protein led to the diagnosis of Creutzfeldt-Jakob's disease. The patient died 14 months after the first neuroophthalmologic signs. The diagnosis was established by post-mortem examination and immuno-electrophoretic demonstration of type 1 prion protein. CONCLUSION: Heidenhain's form of Creutzfeldt-Jakob's disease highlights the importance of general rules for prevention of iatrogenic hazard during ophthalmological examinations.     

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     

New-variant Creutzfeldt-Jakob disease

Surveillance of Creutzfeldt-Jakob disease (CJD) was reinstituted in the United Kingdom in 1990 to monitor any effects of the bovine spongiform encephalopathy (BSE) agent on humans. In 1996, the CJD Surveillance Unit described a new variant of CJD, characterised by an unusually early age of onset, a prolonged clinical course with presenting features that were unusual for CJD, and a characteristic neuropathology. All patients were homozygous for methionine at codon 129 in the prion protein gene, with no mutations or insertions. At present, 23 patients have been diagnosed with this new disorder, but it is impossible at present to predict likely numbers of future cases. Strain typing studies in experimental mice have shown that the transmissible agent in new-variant CJD has identical features to that of the BSE agent, but differs from that in sporadic CJD. The identification of disease-associated prion protein in lymphoid tissue in newvariant CJD raises the possibility of lymphoid biopsy for early diagnosis, and indicates that the transmissible agent may be present in association with circulating lymphoid cells in the blood and other tissues. Although the mode of transmission of the BSE agent to humans is unknown, current evidence favours a dietary mode of spread. However, the precise route of spread, infectious dose and incubation period for BSE in humans are all unknown. Additional studies are required to provide further information, which will allow a more accurate understanding of disease pathogenesis and prediction of future disease trends.     

Bovine spongiform encephalopathy and Creutzfeldt-Jakob disease: facts and uncertainties underlying the causal link between animal and human diseases

Abstract. Following an outbreak of bovine spongiform encephalopathy (BSE) in dairy cows in the United Kingdom (UK), 153 definite and probable human cases of new variant Creutzfeldt-Jakob disease (nvCJD) have been reported, almost exclusively in the UK. Although exposure to the BSE agent is the most plausible interpretation for the occurrence of nvCJD, the causal link between the BSE prion and nvCJD is still debated. This review discusses the pros and cons of nvCJD as a separate nosographic entity, the scientific basis for a correlation between BSE and nvCJD, the validity of the current diagnostic criteria for CJD and nvCJD, the contribution of epidemiology to the detection of a causal relation between BSE and nvCJD, and the present and future directions of the epidemiological research on BSE, CJD and nvCJD.     

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.     

散发型克-雅病的临床特点分析

目的探讨散发型克-雅病(sporadic Creutzfeldt-Jakob disease,s CJD)的临床特点,以期更好地指导临床医师早期发现该病。方法纳入s CJD患者17例,分析其临床特点、早期症状、辅助检查结果以及生存期等。结果男女比例为1:1.83,平均发病年龄为(60±8.8)岁,首发症状以行走不稳(82.4%)、记忆力减退(64.7%)为主,其中,肌阵挛、磁共振"绸带征"、基底节异常信号、脑电图三相波、脑脊液14-3-3蛋白的阳性率分别为82.4%、76.5%、58.8%、82.4%、70%。随访过程中,12例患者已死亡,平均生存期为(12±7.7)个月。结论本研究中,s CJD患者多数中老年发病,首发症状无特异性,磁共振"绸带征"及脑电图三相波阳性出现的几率较高。     

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.