Continuing Education Column Human Prion Diseases SangYun Kim, MD Department of Neurology, Clinical Neuroscience Center, Seoul National University Bundang Hospital E - mail : neuroksy@snu.ac.kr Hae-Kwan Cheong, MD Department of Social and Preventive Medicine, Sungkyunkwan University College of Medicine E - mail : hkcheong@skku.edu Seong Soo An, PhD Department of Bionanotechnology, KyungWon University Gachon Bionanotechnology Research Institute E - mail : seongaan@kyungwon.ac.kr J Korean Med Assoc 2008; 51(12): 1125-1138 Abstract Transmissible Spongiform Encephalopathy (TSE) or prion diseases are fatal neurodegenerative diseases, which are caused by transmissible abnormal prion proteins, converting the endogenous normal prion in the body to the infectious abnormal prions. The most common form of human prion diseases is Creutzfeldt - Jakob disease (CJD). Most of CJD are sporadic with unknown cause. Some familial or iatrogenic CJDs are reported in many countries, but there have been no formally reported case in Korea. Variant CJD (vcjd) is a new form of human prion disease, which revealed differentiated clinical presentations and laboratory diagnostic results. vcjd was thought to be originated from eating the beefs or other parts of bovine spongiform encephalopathy (BSE) infected cattle. The unpredictable species barriers, the underestimated distribution of prion infected tissues, the variable clinical courses, and uncertain disease progressions of many prion diseases, all made the prion related risk assessment very difficult. Korea needs our own surveillance system for various prion diseases of human and animals and to make plans for the risk assessment of the various prion disease transmissions for the minimal spread by maximizing the research capacities. Keywords: Prion; Creutzfeldt - Jakob disease; Variant Creutzfeldt - Jakob disease; Transmissible spongiform encephalopathy 1125
Kim SY Cheong HK An SS Table 1. Comparison between sporadic and variant Creutzfeldt-Jakob disease Sporadic CJD Variant CJD Median age at death 68 years 28 year (18~53 year) Median duration of illness 4~5 months 13~14 months (8~38 months) Main clinical features Onset with rapidly progressive dementia Onset with psychiatric features Cerebellar ataxia Cerebellar ataxia Cortical blindness Dystonia / Chorea Pyramidal signs Pain / other sensory symptoms Myoclonic jerks Oculomotor symptoms Pyramidal signs Dementia Myoclonus Distribution Worldwide Mainly UK Cause Unknown BSE infection in diet Familial cases 10~15% No EEG Generalized theta and delta slowing only or Nonspecific slow waves only normal at early stage Sometimes normal even with Characteristic 1~2Hz triphasic sharp waves neurological symptoms in more than 80%before death CSF Normal cytology and chemistry except mildly Positive 14-3-3 protein in increased protein less than 50% Usually positive 14-3-3 protein Brain CT No specific finding. Cortical atrophy with ventriculomegaly at late stage Brain MRI Asymmetric cortical high signal lesion on Pulvinar sign in more than 75% diffusion weighted MR images High signal lesion on both basal ganglia, caudate nucleus and thalamus Cortical atrophy and enlarged ventricles PRNP 129 codon genotype Relatively high rate of methioine homozygotes Methionine homozygotes in all tested vcjd cases Florid plaques in pathology Rare or absent Present in large numbers Immunohistochemistry Variable accumulation of protease-resistant Marked accumulation of proteaseprion protein resistant prion protein Presence of prion in lymphoid tissue Not readily detected Readily detected Tonsil biopsy as a diagnostic tool Not beneficial Highly recommended 1126
Human Prion Diseases Figure 1. Relationship of animal and human prion diseases. 1127
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Human Prion Diseases Figure 2. Diffusion weighted images (lower line) of sporadic Creutzfeldt-Jakob disease show asymmetrical high signal intensities along the gyrus, which were not so clear in T2W images (upper line). 1131
Kim SY Cheong HK An SS Figure 3. Periodic sharp waves at about 1.5/sec; diffuse, bilateral, slightly asymmetrical: and maximal over the anterior portions of the brain. 1132
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Kim SY Cheong HK An SS Figure 4. A Pulvinar sign (arrows) of variant Creutzfeldt-Jakob disease (MR flair image) (from internet). 1134
Human Prion Diseases 11. Kong Q, Huang S, Zou W, Vanegas D, Wang M, Wu D. Chronic wasting disease of elk: transmissibility to humans examined by transgenic mouse models. J Neurosci 2005; 25: 7944-7949. 12. Marsh RF, Kincaid AE, Bessen RA, Bartz JC, Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus). J Virol 2005; 79: 13794-13796. 13. Global surveillance, diagnosis and therapy of human trans- 1135
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