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Familial Creutzfeldt–Jakob disease with the E200K mutation: longitudinal neuroimaging from asymptomatic to symptomatic CJD

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Abstract

Familial Creutzfeldt–Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. While carriers are born with this mutation, they usually remain asymptomatic until middle age. Early detection of conversion is crucial for understanding and eventually for the treatment of the disease. The aim of this study was to report longitudinal MRI data in E200K individuals who eventually converted from healthy mutation carriers to clinically symptomatic CJD. As a part of a prospective study, asymptomatic E200K mutation carriers were scanned annually until their conversion to symptomatic disease. Standardized diffusion and anatomical MR sequences were performed before and after clinical conversion in the subjects and those were compared to 15 non-carrier siblings (“healthy controls”). Blinded radiological readings and region of interest analyses were performed. Radiological readings of individual cases failed to detect characteristic changes in the scans taken before the conversion. Region of interest analysis of diffusion changes in pre-symptomatic stage was inconclusive; however, ADC reduction was found in early and late stages of the disease. Computerized volumetric analysis revealed monotonic volume reductions in thalamus, putamen and caudate following conversion, and the lateral ventricles showed dilatation of up to 62 % after clinical conversion. Although the clinical manifestations at disease onset are variable, the diffusion abnormalities and/or volume changes in the thalamus and basal ganglia during conversion may indicate early involvement of the thalamostriatal neuronal circuit.

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Acknowledgments

This study was supported by the NIH Grant #NS043488.

Conflicts of interest

Dr. Cohen declares that he has no conflict of interest, Prof. Chapman declares that he has no conflict of interest, Prof. Korczyn declares that he has no conflict of interest, Dr. Nitsan declares that he has no conflict of interest, Dr. Appel declares that he has no conflict of interest, Dr. Hoffmann declares that he has no conflict of interest, Dr. Rosenmann declares that she has no conflict of interest, Prof. Kahana declares that she has no conflict of interest, Dr. Lee declares that he has no conflict of interest.

Informed consent

As stated in the text, all persons gave their informed consent prior to their inclusion in the study and details that might disclose the identity of the subjects under study were omitted.

Ethical standard

The authors declare that this study has been approved by the institutional ethics committees and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Author information

Authors and Affiliations

  1. Department of Neurology and the Sagol Neuroscience Center, Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel

    Oren S. Cohen & Joab Chapman

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Oren S. Cohen, Joab Chapman & Amos D. Korczyn

  3. Barzilai Medical Center, Ashkelon, Israel

    Zeev Nitsan, Shmuel Appel & Esther Kahana

  4. Department of Radiology, Chaim Sheba Medical Center, Tel Hashomer, Israel

    Chen Hoffmann

  5. Hadassah University Hospital, Jerusalem, Israel

    Hanna Rosenmann

  6. Department of Anesthesiology, State University of New York at Stony Brook, Stony Brook, NY, USA

    Hedok Lee

  7. Department of Radiology, State University of New York at Stony Brook, Stony Brook, NY, USA

    Hedok Lee

Authors
  1. Oren S. Cohen
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  2. Joab Chapman
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  3. Amos D. Korczyn
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  4. Zeev Nitsan
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  5. Shmuel Appel
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  6. Chen Hoffmann
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  7. Hanna Rosenmann
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  8. Esther Kahana
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  9. Hedok Lee
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Corresponding authors

Correspondence to Oren S. Cohen or Hedok Lee.

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Cohen, O.S., Chapman, J., Korczyn, A.D. et al. Familial Creutzfeldt–Jakob disease with the E200K mutation: longitudinal neuroimaging from asymptomatic to symptomatic CJD. J Neurol 262, 604–613 (2015). https://doi.org/10.1007/s00415-014-7615-1

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  • DOI: https://doi.org/10.1007/s00415-014-7615-1

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