Clinical findings and diagnosis in genetic prion diseases in Germany

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.

The insomnia phenotype in genetic Creutzfeldt–Jakob disease based on the E200K mutation

“…Our findings, with the presence of FLAIR and DWI hyperintensities in basal ganglia of over 70% in both groups of gCJD E200K, slightly exceed the 58% proportion in the study of 20 German gCJD E200K. Other temporal abnormalities were not analysed in that study [20].…”

Rare E196A mutation in PRNP gene of 3 Chinese patients with Creutzfeldt-Jacob disease

“…However, there are some differences between those 2 mutations. Four German E196K gCJD cases belong to 2 families, 12 while none of three E196A gCJD cases has disease-associated family history. The median onset age of E196A gCJD cases are 71 y and disease duration is relatively short (6.5 months).…”

“…However, another point-mutation in this codon, E196K, has been described in Caucasian, which is causally linked to human prion disease. 11 Majority E196K gCJD cases distributes in Germany, [12][13][14] one in France, 15 one in Italy 16 and one in China. 17 E196K gCJD patients usually present nonspecific symptoms at onset and display the features typical of sCJD during disease progression.…”

Genetic prion disease: Experience of a rapidly progressive dementia center in the United States and a review of the literature

“…In CSF, 14-3-3 positivity has been reported in 85-100% of cases depending greatly on the mutation and the study [Kovacs et al, 2005;Krasnianski et al, 2016], and elevated total tau levels (> 1200 pg/ml), in 75-100% of cases [Breithaupt et al, 2013;Higuma et al, 2013;Krasnianski et al, 2016]. PSWCs in EEG are observed in 11-93% (average ~60-70%) of cases, also depending greatly on the mutation and the study [Breithaupt et al, 2013;Higuma et al, 2013;Kovacs et al, 2005;Krasnianski et al, 2016;Meiner et al, 1997]. The sensitivity of brain MRI varies greatly depending on MRI sequences used, with much lower sensitivity for T2weighted sequences and very high for diffusion sequences (DWI and ADC).…”