Neuropathological Diagnostic Criteria for Creutzfeldt-Jakob Disease (CJD) and Other Human Spongiform Encephalopathies (Prion Diseases)
Corresponding Author
Herbert Budka
Institute of Neurology, University of Vienna, Vienna, Austria
Corresponding author: Dr. Herbert Budka, Institute of Neurology, University of Vienna, Neues AKH, POB 48, A–1097 Wien, Austria. Tel.+43–1–40400–5501; Fax +43–1–40400–5511Search for more papers by this authorAdriano Aguzzi
Institute of Neuropathology, University of Zurich, Zurich, Switzerland
Search for more papers by this authorPaul Brown
Laboratory of Central Nervous System Studies, NINDS, NIH, Bethesda, MD, USA
Search for more papers by this authorJean-Marie Brucher
Neuropathology Unit, Catholic University Louvain, Brussels, Belgium
Search for more papers by this authorOrso Bugiani
National Institute of Neurology C. Besta, Milan, Italy
Search for more papers by this authorFilippo Gullotta
Institute of Neuropathology, University of Müster, Münster, FRG
Search for more papers by this authorMatti Haltia
Institute of Pathology, University of Helsinki, Helsinki, Finland
Search for more papers by this authorJean-Jacques Hauw
Neuropathological Laboratory R. Escourolle, Hǒpital de la Salpětriere, Paris, France
Search for more papers by this authorJames W. Ironside
Neuropathology Laboratory, Department of Pathology, Western General Hospital, Edinburgh, UK
Search for more papers by this authorKurt Jellinger
Neuropathological Laboratory, Department of Neurology, Lainz Hospital, Vienna, Austria
Search for more papers by this authorHans A. Kretzschmar
Institute of Neuropathology, University of Göttingen, Göttingen, FRG
Search for more papers by this authorPeter L. Lantos
Department of Neuropathology, Institute of Psychiatry, University of London, London, UK
Search for more papers by this authorCarlo Masullo
Institute of Neurology, Catholic University of the Sacred Heart, Rome, Italy
Search for more papers by this authorWolfgang Schlote
Neurological Institute, University of Frankfurt, Frankfurt, FRG
Search for more papers by this authorJun Tateishi
Department of Neuropathology, Institute of Neurology, Kyushu University, Fukuoka, Japan
Search for more papers by this authorRoy O. Weller
Neuropathology, Southampton University Hospital, Southampton, UK
Search for more papers by this authorCorresponding Author
Herbert Budka
Institute of Neurology, University of Vienna, Vienna, Austria
Corresponding author: Dr. Herbert Budka, Institute of Neurology, University of Vienna, Neues AKH, POB 48, A–1097 Wien, Austria. Tel.+43–1–40400–5501; Fax +43–1–40400–5511Search for more papers by this authorAdriano Aguzzi
Institute of Neuropathology, University of Zurich, Zurich, Switzerland
Search for more papers by this authorPaul Brown
Laboratory of Central Nervous System Studies, NINDS, NIH, Bethesda, MD, USA
Search for more papers by this authorJean-Marie Brucher
Neuropathology Unit, Catholic University Louvain, Brussels, Belgium
Search for more papers by this authorOrso Bugiani
National Institute of Neurology C. Besta, Milan, Italy
Search for more papers by this authorFilippo Gullotta
Institute of Neuropathology, University of Müster, Münster, FRG
Search for more papers by this authorMatti Haltia
Institute of Pathology, University of Helsinki, Helsinki, Finland
Search for more papers by this authorJean-Jacques Hauw
Neuropathological Laboratory R. Escourolle, Hǒpital de la Salpětriere, Paris, France
Search for more papers by this authorJames W. Ironside
Neuropathology Laboratory, Department of Pathology, Western General Hospital, Edinburgh, UK
Search for more papers by this authorKurt Jellinger
Neuropathological Laboratory, Department of Neurology, Lainz Hospital, Vienna, Austria
Search for more papers by this authorHans A. Kretzschmar
Institute of Neuropathology, University of Göttingen, Göttingen, FRG
Search for more papers by this authorPeter L. Lantos
Department of Neuropathology, Institute of Psychiatry, University of London, London, UK
Search for more papers by this authorCarlo Masullo
Institute of Neurology, Catholic University of the Sacred Heart, Rome, Italy
Search for more papers by this authorWolfgang Schlote
Neurological Institute, University of Frankfurt, Frankfurt, FRG
Search for more papers by this authorJun Tateishi
Department of Neuropathology, Institute of Neurology, Kyushu University, Fukuoka, Japan
Search for more papers by this authorRoy O. Weller
Neuropathology, Southampton University Hospital, Southampton, UK
Search for more papers by this authorAbstract
Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human transmissible spongiform encephalopathies (prion diseases) are proposed for the following disease entities: CJD - sporadic, iatrogenic (recognised risk) or familial (same disease in 1st degree relative): spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter; or encephalopathy with prion protein (PrP) immuno-reactivity (plaque and/or diffuse synaptic and/or patchy/perivacuolar types). Gerstmann-Sträussler-Scheinker disease (GSS) (in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multicentric PrP plaques. Familial fatal insomnia (FFI) (in member of a family with PRNP178 mutation): thalamic degeneration, variable spongiform change in cerebrum. Kuru (in the Fore population).
Without PrP data, the crucial feature is the spongiform change accompanied by neuronal loss and gliosis. This spongiform change is characterised by diffuse or focally clustered small round or oval vacuoles in the neuropil of the deep cortical layers, cerebellar cortex or subcortical grey matter, which might become confluent. Spongiform change should not be confused with non-specific spon-giosis. This includes status spongiosus (“spongiform state”), comprising irregular cavities in gliotic neuropil following extensive neuronal loss (including also lesions of “burnt-out” CJD), “spongy” changes in brain oedema and metabolic encephalopathies, and artefacts such as superficial cortical, perineuronal, or perivascular vacuolation; focal changes indistinguishable from spongiform change may occur in some cases of Alzheimer's and diffuse Lewy body diseases. Very rare cases might not be diagnosed by these criteria. Then confirmation must be sought by additional techniques such as PrP immunoblotting, preparations for electron microscopic examination of scrapie associated fibrils (SAF), molecular biologic studies, or experimental transmission.
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