CJD Cases Research Articles

Prion protein accumulation in the spinal cords of patients with sporadic and growth hormone associated Creutzfeldt-Jakob disease

An immunohistological study of the spinal cord in 20 cases of sporadic and 4 iatrogenic (growth hormone) cases of Creutzfeldt-Jakob (CJD) disease patients was performed to detect the presence of disease specific prion protein using a number of different antisera. Prion protein was present in all the growth hormone recipients and in 11 of the 20 sporadic CJD cases. Plaque-like deposits of prion protein were found in all the growth hormone cases and three of the sporadic cases. This is the first demonstration of the topographic immunolocalisation of prion protein in the spinal cord of CJD patients, a feature which could help elucidate some important aspects of the pathogenesis of CJD.

CJD cases being misdiagnosed as Alzheimer’s

CJD cases being misdiagnosed as Alzheimer’s

Neuropathology of spongiform encephalopathies in humans

The historical aspects and classification of human spongiform encephalopathies are reviewed and the newer concept of 'prion dementias' is explored. Guidelines for safe laboratory and autopsy handling of spongiform encephalopathy tissues are outlined: this includes an update on strategies which are currently thought to be effective in decontamination. A wide ranging review of the pathology of the various human spongiform encephalopathies includes newly emerging data on microglia, and cell-specific and neurodegenerative proteins. A large section of this chapter is devoted to the methodology of immunocytochemical demonstration of PrP in tissue sections, and the dilemmas inherent in interpretation. Clinicopathological correlations are provided for classical cases of spongiform encephalopathy, together with the newly recognised atypical dementias associated with PrP gene mutations. The pathology of iatrogenic cases of CJD is described. The chapter concludes with problems in differential diagnosis, and discussion of the histopathological features which help to resolve diagnostic dilemmas.

The biology and molecular biology of scrapie-like diseases.

The transmissible spongiform encephalopathies (TSE's) are degenerative diseases of the central nervous system which naturally affect man (Creutzfeldt-Jakob disease [CJD], Gerstmann-Sträussler syndrome [GSS], kuru), sheep and goats (scrapie), cattle (bovine spongiform encephalopathy [BSE]), mink (transmissible mink encephalopathy), mule deer, elk and antelope (chronic wasting disease). Spongiform encephalopathies have also been diagnosed in captive species of zoo antelope and in domestic cats. Much has been written about these maladies in the wake of the BSE outbreak, the tragic cases of CJD in recipients of cadaver-derived human growth hormone, sex hormones or dura mater and this has stimulated a continuing public health debate about the transmissibility, prevalence and clinical variability of scrapie, CJD and related ("prion") diseases. Prions (Weissmann, Liautard, this volume) and the human (Kretzschmar, this volume) and cattle (Wilesmith, Marsh, this volume) diseases are described in more detail elsewhere. This article presents a brief overview of the biology and molecular cell biology of scrapie and rodent models of these diseases.

PrP amyloid plaques in Creutzfeldt-Jakob disease of short duration: immunohistochemical studies of 5 cases from Poland.

We report here PrP-immunohistochemistry performed on brains from CJD cases from Poland. Only one of five definitive CJD cases exhibited typical PrP-immunoreactive kuru-like plaques and this was case of a short duration. We thus confirm the low frequency of PrP plaques in CJD of Eastern and Central European origin.

Creutzfeldt-Jakob disease ? clinical picture analysis

The early, late, and terminal features of (CJD) were analyzed, based on the clinical histories and picture evolution of 12 histologically-confirmed cases of CJD. The most essential features observed were sensorimotor disintegration, and impairment of both mental and higher cortical functions, occurring in various combinations. On the basis of a sampling of early symptoms and signs we were able to make an early differential diagnosis.

The transmissible amyloidoses: Genetical control of spontaneous generation of infectious amyloid proteins by nucleation of configurational change in host precursors: Kuru-CJD-GSS-Scrapie-BSE

Kuru, Creutzfeld-Jakob disease, Gerstmann-Sträussler syndrome, scrapie, and bovine spongiform encephalopathy are caused by so-called unconventional viruses which are really replicating proteins which induce by auto nucleation and autopatterning a configurational change in the precursor protein to produce an infectious amyloid form. Crystallography and NMR may eventually determine how amyloid precursor protein is converted to this infectious form by configurational changes in all tertiary and quaternary structure of the normal precursor. Most sporadic cases of CJD arise by de novo spontaneous conversion of the normal precursor to the infectious form, a rare event occurring at the frequency of one per million persons per year (the annual incidence of CJD throughout the world). In the familial forms of CJD and GSS, where the occurrence is an autosomal dominant trait, each family has one of five different mutations causing a single amino acid change or one of five insertions of 5, 6, 7, 8 or 9 octapeptide repeats. Each mutation causes a million-fold increased probability of the spontaneous configurational change to an infectious polypeptide, and appears as an autosomal dominant trait. Thus, the behavior of the transmissible brain amyloidosis parallels completely that of the transthyretin amyloidoses causing familial amyloidotic polyneuropathy, in which there are 19 different point mutations, each one of which increases enormously the likelihood of configurational change of transthyretin prealbumin to amyloid.

“Clusters” of CJD in Slovakia: The first laboratory evidence of scrapie

Epidemic-like occurrence of Creutzfeldt-Jakob disease was observed in 1987 in Slovakia (Orava). Search for the cause of CJD focus indicated a coincidence of genetic and environmental risks in clustering patients. Since Spongiform Encephalopathies might be transmitted orally, (Bovine Spongiform Encephalopathy), the possibility of zoonotic source of CJD cases in Orava was also considered. A deficient knowledge about the occurrence of scrapie in Slovakia stimulated an examination of sheep with signs of CNS disorders in two flocks of Valasky breed in Orava. In one flock, neurohistopathological examination revealed in sheep brains lesions characteristic for scrapie. Frozen brain tissue of these animals were used for the detection of scrapie associated fibrils. They were found in 2 animals from the same flock. This is the first laboratory confirmation of scrapie in Czecho-Slovakia. The possible epidemiological and economical implications are emphasized.

?Clusters? of CJD in Slovakia: The first statistically significant temporo-spatial accumulations of rural cases

A space-time analysis of clustering among 78 definite CJD cases who died in Slovakia (75) and an adjacent part of Hungary (3) during 1972-1991 is presented. Two geographical rural accumulations of sporadic and familial CJD patients in the north and south of Central Slovakia were found. There was evidence of two significant clusters when spatial and temporal neighborhoods were defined by distances of 2,4,5 and 7 km within 1.5 and 2 years. Involvement of genetic mechanisms in the clusters was demonstrated, and the possible role of environmental (zoonotic) risk factors are considered.

Erratum: Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob disease

Nature 352, 340-342 (1991) IN this letter in the 25 July issue, the sentence beginning in line 1 on page 341 should read: "Of the 22 CJD cases, 16 were homozygous for Met 129, 5 homozygous for Val 129 and only one was a heterozygote, while of the suspected CJD cases, 13 were Met-129 homozygotes, 4 were heterozygotes and 6 were Val-129 homozygotes.

Creutzfeldt-Jakob Disease with Periodic Lateralized Discharge: Case Report

A case of CJD with PLD in the first EEG is reported. The PLD became bilateral in the next EEG. The subsequent EEGs showed shifting asymmetries. In this case, PSD reappeared after 5 months' absence. The PLD occasionally appeared over the hemisphere ipsilateral to the side of the myoclonic jerks. The clinical significance of the PLD and reappearance of PD, and the diagnostic importance of PLD are discussed.

Spongiform encephalopathy with extensive involvement of white matter

We report a proven case of CJD with a prolonged clinical course and white matter involvement which consisted of severe, widespread myelin damage in the forebrain and cerebellum but with sparing of the internal capsule. Histologically, there was status spongiosus of the involved white matter with axonal loss, proliferation of hypertrophic astrocytes and scattered and perivascular foamy macrophages. White matter lesions have not been considered to be a significant feature of CJD. In the last few years, however, a few cases have been described with prominent degeneration of cerebral white matter. We believe that our findings corroborate the existence of an entitythat at present may only be defined as spongiform panencephalopathy.

Creutzfeldt-Jakob Disease

There has been significant advance in our understanding of CJD and similar spongiform encephalopathies in recent years. The range in clinical expression of the disease is better appreciated, and the existence of "atypical" cases of CJD is increasingly recognized. New ideas about the possible modes of natural transmission have been derived from case-control studies in different parts of the world.

Failure to detect scrapie virus in sheep at slaughter in a highly endemic region of France.

A study was carried out in a sheep slaughterhouse located in a region of France where scrapie has been endemic for several decades. Neuropathological examination of 63 randomly selected lambs and adult sheep revealed no scrapie-related abnormalities, and inoculation of mice with brain, tonsil, lateropharyngeal ganglia, and intestine from the same animals did not transmit scrapie. The failure to detect any evidence of scrapie infection in commercially-bred sheep, the absence of an increased mortality rate for human CJD in the surrounding consumer region, and the absence of a single case of CJD among slaughterhouse personnel, do not support the hypothesis that exposure to potentially scrapie-contaminated products is responsible for CJD in humans.

On the white matter lesions of the Creutzfeldt-Jakob disease: Can a new subentity be recognized in man?

One case of CJD with severe involvement of the white matter is discussed. The patient was admitted after a 3-month clinical course with rapidly increasing mental deterioration, coma vigil-like state, myoclonic twitching of the limbs and of the facial muscles. The EEG showed the typical features of CJD. The first CT scan, performed 3 months after onset, revealed only a mild cortical and subcortical atrophy of the brain. The second CT scan, 12 months later, showed a considerable cortical and subcortical atrophy of the brain. The patient died 18 months after onset. Neuropathological examination showed a severe degeneration in the gray matter, with spongiosis, loss of neurones and hypertrophic glial reaction. The white matter was also involved with severe spongiosis, demyelination and hypertrophic glial proliferation. The case is discussed in relation to the data in the literature. It is argued that cases of CJD with severe involvement of the white matter should be classified as a new neuropathological subentity of CJD.