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Clinical findings and diagnosis in genetic prion diseases in Germany

  • GENETIC EPIDEMIOLOGY
  • Published:
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Abstract

To describe the clinical syndrome and diagnostic tests in patients with genetic prion diseases (gPD) in Germany. Clinical features, MRI, EEG, and CSF markers were studied in 91 patients (28 D178N, 20 E200K, 17 inserts, 13 V210I, 8 P102L, 5 E196K). Dementia (35 %) and ataxia (29 %) were the most common initial symptoms and signs. A wide variety and high frequency of neurological/psychiatric symptoms and signs was found during disease course in all patients independently of the type of the mutation. Psychiatric manifestations were frequent (87 %). Neuropsychological abnormalities were observed in 67 %, and aphasia was the most common disturbance (45 %). In E200K, V210I and D178N patients, visual/oculomotor deficits were followed by ataxia early in the disease. Dementia followed by ataxia at onset was common in patients with insert and E196K mutation. P102L patients had isolated ataxia over a longer time period followed by pyramidal signs. Dementia was present only late in the disease course. All clinical routine tests such as MRI, EEG and CSF tests were less sensitive than in sporadic CJD. We provide the first detailed analysis of clinical signs and symptoms in a large group of patients with gPD. Frequency of clinical symptoms and signs was similar in different mutations in a later disease course, but the sequence of occurrence may be of great diagnostic importance. CSF markers were shown to be more sensitive than MRI and EEG.

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Acknowledgments

First of all, we thank the patients and their families. The authors thank neurologists and psychiatrists throughout Germany for providing clinical and neuropathological data on patients and for sending CSF and blood samples. We thank Mrs. Henn, Staniszewski, Bodemer and Ciesielczyk for the excellent technical assistance. The assistance of Mrs. Ehrlich and Schneider-Dominco is gratefully acknowledged. This study was funded by the Robert Koch-Institute through funds of the Federal Ministry of Health (Grant Number 1369-341) and the European Commission (FP6-2005-SSP-5-A, 044438).

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Authors and Affiliations

  1. Department of Neurology, National Reference Center for TSE Surveillance, University Medical School, Georg-August University Göttingen, Robert-Koch Str. 40, 37075, Göttingen, Germany

    Anna Krasnianski, Uta Heinemann, Claudia Ponto, Jasmine Kortt, Daniela Varges & Inga Zerr

  2. Department of Neuroradiology, University Medical School, Georg-August University Göttingen, Göttingen, Germany

    Kai Kallenberg

  3. Department of Neuropathology, University Medical School, Georg-August University Göttingen, Göttingen, Germany

    Walter J. Schulz-Schaeffer

  4. Department of Neuropathology, Ludwig-Maximillian University Munich, Munich, Germany

    Hans A. Kretzschmar

  5. Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt, Germany

    Anna Krasnianski

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  1. Anna Krasnianski
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  2. Uta Heinemann
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  7. Walter J. Schulz-Schaeffer
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  8. Hans A. Kretzschmar
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Correspondence to Inga Zerr.

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Krasnianski, A., Heinemann, U., Ponto, C. et al. Clinical findings and diagnosis in genetic prion diseases in Germany. Eur J Epidemiol 31, 187–196 (2016). https://doi.org/10.1007/s10654-015-0049-y

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  • DOI: https://doi.org/10.1007/s10654-015-0049-y

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