Journal of Neurology

, Volume 260, Issue 7, pp 1871–1879 | Cite as

Spongiform encephalopathy in siblings with no evidence of protease-resistant prion protein or a mutation in the prion protein gene

  • Daniela Varges
  • Walter J. Schulz-Schaeffer
  • Wiebke M. Wemheuer
  • Insa Damman
  • Matthias Schmitz
  • Maria Cramm
  • Kai Kallenberg
  • Katayoon Shirneshan
  • Manar Elkenani
  • Susanne Markwort
  • Michael Faist
  • Jürgen Kohlhase
  • Otto Windl
  • Inga Zerr
Original Communication

Abstract

We discuss relevant aspects in two siblings with a neurodegenerative process of unclear aetiology who developed progressive dementia with global aphasia and hyperoral behaviour at the ages of 39 and 46 years and who died 6 and 5 years after disease onset. The cases were reported to the National Reference Center for TSE Surveillance in Göttingen, Germany. Detailed clinical examinations, CSF, blood samples, and copies of the important diagnostic tests (magnetic resonance imaging, electroencephalogram, laboratory tests) were obtained. Further neuropathological and genetic analyses were performed. Cerebral magnetic resonance imaging of both siblings showed prominent changes in signal intensity, especially in the left medial temporal cortex, but also the hippocampal formation. Neuropathological examination revealed spongiform changes, neuronal loss, and astrocytic gliosis, which are typical in Creutzfeldt–Jakob disease. However, no prion protein deposits were detectable by immunohistochemical analysis, Western blot, or PET blot, though abundant tau protein deposits were observed. A mutation in the coding region of the prion protein genes of both siblings was excluded. A detailed search of the literature revealed no other cases with a similar clinical and neuropathological appearance. While the disease aetiology remains unclear, the findings point to a neurodegenerative process and most likely a genetic disease.

Keywords

Dementia Creutzfeldt–Jakob disease MRI Prion protein Tau Early onset dementia 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Daniela Varges
    • 1
  • Walter J. Schulz-Schaeffer
    • 2
  • Wiebke M. Wemheuer
    • 2
  • Insa Damman
    • 2
  • Matthias Schmitz
    • 1
  • Maria Cramm
    • 10
  • Kai Kallenberg
    • 3
  • Katayoon Shirneshan
    • 4
  • Manar Elkenani
    • 5
  • Susanne Markwort
    • 6
  • Michael Faist
    • 7
  • Jürgen Kohlhase
    • 8
  • Otto Windl
    • 9
  • Inga Zerr
    • 1
    • 10
  1. 1.National Reference Center for TSE Surveillance, Department of NeurologyUniversity Medical Center GöttingenGöttingenGermany
  2. 2.Department of NeuropathologyUniversity Medical Center GöttingenGöttingenGermany
  3. 3.Department of NeuroradiologyUniversity Medical Center GöttingenGöttingenGermany
  4. 4.Department of Hematology and OncologyUniversity Medical Center GöttingenGöttingenGermany
  5. 5.Institute of Human GeneticsUniversity Medical Center GöttingenGöttingenGermany
  6. 6.Department of PsychiatryHospital SchlüchternSchlüchternGermany
  7. 7.Department of NeurologyAlbert-Ludwigs-University FreiburgFreiburgGermany
  8. 8.Center for Human GeneticsFreiburgGermany
  9. 9.Molecular Pathogenesis and Genetics DepartmentVeterinary Laboratories AgencyNew HawUK
  10. 10.German Center for Neurodegenerative Diseases (DZNE), Department of NeurologyUniversity Medical Center GöttingenGöttingenGermany

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