Panencephalopathic Type Of Creutzfeldt-Jakob Disease Research Articles

Tumor necrosis factor alpha (TNF-α) is involved in the pathogenesis of the panencephalopathic type of Creutzfeldt-Jakob disease

Tumor necrosis factor alpha (TNF-α) is involved in the pathogenesis of the panencephalopathic type of Creutzfeldt-Jakob disease

Tumor necrosis factor alpha (TNF-α) is involved in the pathogenesis of the panencephalopathic type of Creutzfeldt-Jakob Disease (CJD) : P.P. Liberski 1,2, V.R. Nerurkar 1, R. Yanagihara 1, and D.C. Gajdusek 1; 1LCNSS, NINDS, NIH, Bethesda, Maryland 20892, USA, 2, EM Lab, Dept. Oncology, Medical Academy Lodz, Poland

Tumor necrosis factor alpha (TNF-α) is involved in the pathogenesis of the panencephalopathic type of Creutzfeldt-Jakob Disease (CJD) : P.P. Liberski 1,2, V.R. Nerurkar 1, R. Yanagihara 1, and D.C. Gajdusek 1; 1LCNSS, NINDS, NIH, Bethesda, Maryland 20892, USA, 2, EM Lab, Dept. Oncology, Medical Academy Lodz, Poland

Creutzfeldt- Jakob Disease

We report a case of the unusual panencephalopathic type of Creutzfeldt-Jakob disease (CJD) in Taiwan. This 59-year-old woman presented in 1983 with typical clinical manifestations of CJD and died 16 months later. Postmortem examination revealed severe neuronal loss, spongiosis and gliosis extensively in cerebral cortex and striatum as well as in the white matter. We also report 6 other CJD patients seen from 1983 to 1991 at Veterans General Hospital-Taipei.

Ultrastructural pathology of axons and myelin in experimental scrapie in hamsters and bovine spongiform encephalopathy in cattle and a comparison with the panencephalopathic type of Creutzfeldt-Jakob disease

We report the ultrastructural pathology of axons and myelin sheaths in bovine spongiform encephalopathy (BSE) and experimental scrapie in hamsters and compare it with that found in a panencephalopathic model of Creutzfeldt-Jakob disease (CJD). Intramyelinic vacuoles (myelin ballooning), dystrophic axons, phagocytic astrocytes and macrophages were found in all three models but to different degrees, while axons containing numerous cellular processes and concentric cisterns were observed only in experimental scrapie and CJD. We conclude that axonal and myelin pathology is a widespread phenomenon and the differences between panencephalopathic CJD and polioencephalopathic BSE and scrapie are only quantitative.

Swollen Cortical Neurons in Creutzfeldt-Jakob Disease Contain a Phosphorylated Neurofilament Epitope

The distribution of swollen neurons and the presence of a phosphorylated neurofilament protein (NFP) epitope in these cells were studied in six cases of Creutzfeldt-Jakob disease (CJD). Swollen neurons are widely distributed in the cerebral cortex and are most abundant in the cingulate and parahippocampal gyri. They are more numerous in the panencephalopathic type of CJD than in the subacute spongiform encephalopathic type. A phosphorylated epitope of NFP was detected in the perikarya of swollen neurons by an immunocytochemical method using a series of monoclonal antibodies that distinguish phosphorylated and nonphosphorylated epitopes of NFP. This abnormal distribution of phosphorylated NFP epitopes indicates that the process of NFP phosphorylation is altered in neurons affected by CJD. This investigation, in accordance with previous studies, suggests that the abnormal post-translational modification of the neurofilament may play an important role in the pathogenesis of several neurodegenerative disorders.

Panencephalopathic Type of Creutzfeldt-Jakob Disease with Primary Extensive Involvement of White Matter

The case of a 66-year-old woman with atypical Creutzfeldt-Jacob disease (CJD) presents several peculiarities. Pathologic examination confirmed a rare CJD case with primary generalized spongiform changes of the white matter and only moderate, but typical changes of the gray matter. Besides an essentially typical clinical course, the patient developed temporary diplopia and vertical eye movement paralysis. Intoxication had been excluded. Isoelectric focusing revealed oligoclonal CSF-IgG. Magnetic resonance imaging studies showed periventricular accentuated flat and striped hyperintense structures. EEG had CJD-typical periodic 1/s synchronous discharges. This case illustrates for the first time that in panencephalopathic type of CJD the cerebral white matter can be involved primarily and more extensively than the gray matter.

White matter ultrastructural pathology of experimental Creutzfeldt-Jakob disease in mice

Creutzfeldt-Jakob disease (CJD), previously regarded as a neurodegenerative disorder strictly of the gray matter, occasionally occurs as a panencephalopathic form which is characterized by severe white matter damage. An ultrastructural study of the white matter pathology in mice experimentally infected with the Fujisaki strain of CJD virus revealed: (1) vacuoles within myelin sheaths, formed by splitting either at the major dense or intraperiod lines, or within axons; (2) macrophages filled with numerous myelin figures, lipid droplets and paracrystalline inclusions; (3) astrocytes actively digesting myelin debris; (4) unusual wrapping of several axons by a common myelin sheath; (5) vesicular degeneration of myelin sheaths; (6) close contact between numerous coated pits and outer myelin lamellae; and (7) proliferation of inner mesaxons. Our data indicate that the damage to myelinated axons in the panencephalopathic type of CJD is accomplished primarily by active degradation of myelin by macrophages and astrocytes and by formation of intra-axonal and intra-myelin vacuoles. The myelin vacuolation is most consistent with that produced by leukolysins released from activated macrophages and astrocytes.

Panencephalopathic type of Creutzfeldt-Jakob disease: primary involvement of the cerebral white matter.

Eight necropsy cases of a "panencephalopathic" type of Creutzfeldt-Jakob disease (CJD) in the Japanese are reported. The reasons why this type should be discussed separately from other types of CJD are that there is primary involvement of the cerebral white matter as well as the cerebral cortex, and that the white matter lesion of one Japanese human brain with CJD similar to the present group has been successfully transmitted to experimental animals.