Presence of prion protein in peripheral tissues of Libyan Jews with Creutzfeldt-Jakob disease.

The prion protein (PrP) gene on chromosome 20 encodes a protein designated PrPC. An abnormal, protease-resistant isoform of PrPC, denoted PrPCJD or PrPSc, is present in the brains of patients with Creutzfeldt-Jakob disease (CJD). In Libyan Jews, CJD segregates with a point mutation at codon 200 of the PrP gene, resulting in the substitution of lysine for glutamate. In the present study, we examined the presence of PrP in fibroblasts and leukocytes derived from eight CJD patients with the codon 200 mutation. In cultured fibroblasts as well as in leukocytes, there was a significant increase in PrP as judged by immunocytochemistry in addition to immunoblotting. Most of the PrP in fibroblasts and leukocytes could be released from the external surface by phosphatidylinositol-specific phospholipase C, a property characteristic of PrPC. In leukocytes only, part of the protein was protease resistant, resembling PrPCJD. The concentration of PrP mRNA was similar in fibroblast lines derived from controls and CJD patients. These results suggest that in CJD patients carrying a mutation at codon 200 of the PrP gene, the metabolism of PrP, rather than PrP synthesis, is abnormal.     

Variant Creutzfeldt-Jakob disease: an update

Variant Creutzfeldt-Jakob disease (vCJD) is a novel human prion disease caused by the bovine spongiform encephalopathy agent. Most cases have occurred in the UK, with smaller numbers in 11 other countries. All definite vCJD cases have occurred in methionine homozygotes at codon 129 in the prion protein gene. Following oral infection, the vCJD agent appears to replicate in lymphoid tissues during the asymptomatic phase of the incubation period. At present, four probable cases of vCJD infection have been identified following transfusion of red blood cells from asymptomatic donors who subsequently died from vCJD. Recently, one case of likely transmission of vCJD infection by UK Factor VIII concentrates has been reported in an elderly haemophilic patient in the UK. The recent report of a blood test that may be used to detect vCJD has raised the possibility of a new way to identify infected individuals, perhaps even before the onset of clinical symptoms.     

Genetic and environmental factors determining the development of Creutzfeldt-Jakob disease in Libyan Jews.

The cluster of Creutzfeldt-Jakob disease (CJD) among Jews of Libyan origin is one of the largest in the world. A number of hypotheses have been proposed to account for this cluster, the most prevalent but unsubstantiated hypothesis being that a transmissible agent was ingested in the form of scrapie-infected sheep brains. It has, however, been shown that a modified host protein encoded by the gene specifying the scrapie amyloid precursor is critically involved in the pathogenesis of transmissible spongiform encephalopathies such as CJD, Gerstmann-Strüssler-Scheinker syndrome and Kuru. A mutation at codon 200 in the open reading frame of this gene has recently been linked to a cluster of CJD patients in Slovakia. We examined the prevalence of this mutation among CJD patients of Libyan descent in Israel. All patients were found to have the same codon 200 mutation. These findings implicate this mutation in the high prevalence of CJD among Libyan Jews and Sephardic Jews from other Mediterranean countries.     

Creutzfeldt-Jakob disease in an adolescent

A 16-year-old boy was stricken with a progressive neurologic disorder characterized primarily by dementia progressing to severe neurologic debility in 12 months and death 28 months following the first symptoms. Pathologic examination showed a spongiform encephalopathy, consistent witha clinical diagnosis of Creutzfeldt-Jakob disease (CJD). The noteworthy features of the case are the age of onset, the somewhat prolonged course an the amount of white matter change. These are discussed within the frame of reference of CJD and the spongiform encephalopathies of infancy and childhood. Animal inoculation studies employing post-mortem embalmed brain as inoculum are currently in progress to determine the transmissibility of this patient's disease.     

Do Creutzfeldt-Jakob disease patients of Jewish Libyan origin have unique clinical features?

A focus of Creutzfeldt-Jakob disease is present in Israel among Jews born in Libya. The present study examines the clinical features in this particular group of patients. In a country-wide study of Creutzfeldt-Jakob disease, we identified 114 patients; 49 were Libyan immigrants, and 65 (three of whom had Libyan ancestors) were born in other countries. The clinical presentation and evolution of the disease is very similar in patients born in Libya and others without Libyan ancestors, but it tends to be more classical in the Libyan patients, with higher frequency of myoclonic jerks and periodic EEG and a progressive course of shorter duration. The Libyan patients tend to complain more often of headache, which is most probably an ethnic expression for depression and loss of concentration. There was no difference between the familial and nonfamilial cases.     

Iatrogenic Creutzfeldt-Jakob disease: the waning of an era

The outbreaks of iatrogenic Creutzfeldt-Jakob disease (CJD) from cadaveric human growth hormone and dura mater are winding down and, like the only other environmentally acquired form of CJD (variant CJD due to infection with the agent of bovine spongiform encephalopathy), iatrogenic disease seems to have reached its high water mark during the 1990s. The total number of cases has reached 405, and the diminishing number of new cases is due to extremely long incubation periods from infections acquired before 1985 (up to 23 years for dura mater and 36 years for growth hormone). Although no cases associated with surgical or other invasive procedures have been identified during the past several decades, the recent discovery of three transfusion-associated variant CJD infections has provoked new concerns about the possibility of further secondary transmissions from operative procedures as well as blood and tissue donations. Therefore, at least in those countries in which variant CJD has occurred, precautionary measures must continue for the indefinite future.     

Deafness: an unusual onset of genetic Creutzfeldt-Jakob disease

We describe a case of genetic Creutzfeldt-Jakob disease (CJD) with deafness at the onset. We report clinical features, 14-3-3 protein positivity, electroencephalography and brain stem auditory evoked potential abnormalities, and high signal on magnetic resonance imaging in basal ganglia and temporal cortex. Similarities with CJD Heidenhain variant are discussed. Received: 27 October 1999 / Accepted in revised form: 30 January 2000     

Creutzfeldt-Jakob disease cluster in an Australian rural city

Through the Australian National Creutzfeldt-Jakob Disease Registry, 6 pathologically confirmed sporadic cases were recognized over a 13-year period in persons who had been long-term residents of a moderate-sized rural city, whereas the expected number was 0.923. An extensive investigation could not find any point-source or case-to-case transmission links. This occurrence is highly statistically significant (p = 0.0027) when viewed in isolation and remains significant (p < 0.02) when only the cases that arose after the cluster was recognized were taken into account. However, a more conservative statistical analysis suggests that such a grouping could have arisen by chance in at least one population group of this size when the whole country is taken into consideration.     

Creutzfeldt-Jakob disease: a disease overview

Creutzfeldt-Jakob disease (CJD) is the most common form of the human transmissible spongiform encephalopathies, also known as prion diseases. This is a rare neurological disorder which ultimately results in death. Technologists must familiarize themselves with the clinical symptoms and EEG patterns of this disease since appropriate precautions must be taken. This is especially important when running electroneurodiagnostic (END) studies on patients with rapidly progressive dementia or a suspected or known case of CJD. An overview of the various forms of CJD, clinical symptoms, characteristic EEG results, transmission modes, diagnostic tests, and prevention methods are addressed.     

Creutzfeldt-Jakob disease with tubulovesicular structures: an ultrastructural study.

Tubulovesicular structures (TVS) have been consistently observed in brain tissue of the transmissible spongiform virus encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy and experimentally induced Creutzfeldt-Jakob disease (CJD). TVS were recently demonstrated in 3 cases of naturally occurring CJD. We report here the presence of TVS in another human brain with CJD, as detected in all 3 specimens by thin section electron microscopy. Their occurrence in all types of spongiform encephalopathies, irrespective of the affected host and the strain of infectious agent, emphasizes their biological significance.     

Creutzfeldt-Jakob disease in Sweden

OBJECTIVES—To find and investigate,retrospectively, as many cases as possible ofCreutzfeldt-Jakob disease (CJD) in Sweden dying during the period1 January 1985 to 31 December 1996 and to detect any possible case(s)of new variant CJD.
METHODS—The patients were found through computersearch of all death certificates in Sweden on which CJD was mentioned,through information from the Swedish neuropathologists, and spontaneousreports from Swedish doctors and hospitals. Data concerning thepatients were then collected from patients' case records and frombrain histopathology reports.
RESULTS—In total 72 cases of spongiformencephalopathy were confirmed as definite by neuropathology, one ofthem with Gerstmann-Stäussler-Scheinker disease. In 51 further casesthere were no brain pathology data but the diagnosis "probable" (37 patients) or "possible" (14 patients) CJD according to WHO criteriacould be made on clinical grounds. There was a variation in number ofdeaths/year, from a minimum of five (1985) to a maximum of 16 (1990).Sixty patients died during the period 1985-90 and 62 during 1991-6.The sex ratio was nearly 1:1. Calculated for a population of 8.6 million (mean of 12 years) in Sweden this gives 1.18/million/year. Ageat the time of the presenting symptoms ranged from 34 to 84 years. Only one patient was under 40 at the onset of symptoms. He had a spongiform encephalopathy but prion protein staining was negative. The duration ofsymptoms that could be attributed to CJD was 6 months or less in 75 cases, 7-12 months in 16 cases, 1 to 2 years in 15 cases, and morethan 2 years in 16 patients. By definition all patients were demented.Other more common symptoms and signs were aphasia, dysphasia,dysathria, ataxia, myoclonus, pareses of the extremities, rigidity orspasticity, different types of hyperkinesias, and other psychiatricsymptoms (depression, anxiety, and aggressiveness). Less commonsymptoms were hallucinations (mainly visual), visual defects, sensorysymptoms (paraesthesias, itching, or pain), apraxia of swallowing, anddisorders of eye movements.
CONCLUSIONS—The incidence, the symptomatology, theage distribution (age in years at onset and at death), and the durationof illness were similar to those of other countries except for thecases of new variant CJD in the United Kingdom. There is so far noindication of any cases of new variant CJD in Sweden.

     

Creutzfeldt-Jakob disease in Japan

In a nationwide survey of Creutzfeldt-Jakob disease (CJD) in Japan, the point prevalence rate on June 1, 1978 in Fukuoka Prefecture and the estimated national prevalence rate were approximately one per one million population. The minimal period prevalence rate was 0.45 per one million population. The minimal annual incidence and the minimal annual mortality rate were 0.19 and 0.15 per one million population, respectively. The geographic distribution of CJD in Japan was uniform. Clinically, CJD affected the central nervous system diffusely and was rapidly fatal. No specific features were found in family, social, and past histories.     

Creutzfeldt-Jakob disease in Hungary

Human prion diseases or transmissible spongiform encephalopathies are progressive fatal neuropsychiatric diseases. In addition to the evaluation of clinical features, a common diagnostic procedure includes examination of the protein 14-3-3 in the cerebrospinal fluid, performing EEG to detect periodic sharp wave complexes with triphasic morphology, and cranial MRI to demonstrate high signal intensity in the basal ganglia or thalamus. The definite diagnosis requires a neuropathological examination. The analysis of the prion protein gene (PRNP) is initiated mainly after suspicion of a positive family history or an atypical presentation. In Hungary collecting data and setting up the neuropathological diagnosis in suspect prion disease cases originates from the late 1960s. Systematic surveillance was established in 1994 and since 2001 reporting of Creutzfeldt-Jakob disease has been compulsory. According to our database, the incidence of genetic prion disease is increased in Hungary. The most frequent mutation in the PRNP is at codon 200. This might be linked to migration from the Slovakian focus. Acquired forms of prion disease were not detected in our country. The surveillance system is based on referrals from clinicians and pathologists and the aim is to perform the neuropathological examination and analysis of the PRNP on the majority of suspect cases.     

Neuropathologic verification of Creutzfeldt-Jakob disease in the exhumed American recipient of human pituitary growth hormone: epidemiologic and pathogenetic implications

Beginning at age 12, a boy with idiopathic hypopituitarism was treated with cadaver pituitary-derived human growth hormone during the period from 1963 to 1969. Fifteen years after the last treatment, the then 32-year-old man developed Creutzfeldt-Jakob disease (CJD). The illness was atypical in showing predominantly cerebellar signs, little mental deterioration, and no abnormal movements or periodic EEG activity. Examination of the embalmed brain, 7 months after interment, revealed the characteristic changes of CJD mainly in the cerebellum and basal ganglia. This case establishes the contamination of at least two American lots of human growth hormone and, together with other cases of iatrogenic disease, suggests that virus enters the brain from the blood, rather than along neural pathways.