Heinemann, Uta

[["dc.bibliographiccitation.firstpage","2288"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","2296"],["dc.bibliographiccitation.volume","129"],["dc.contributor.author","Krasnianski, Anna"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Kallenberg, Kai"],["dc.contributor.author","Meissner, Bettina"],["dc.contributor.author","Collie, Donald A."],["dc.contributor.author","Roeber, Sigrun"],["dc.contributor.author","Bartl, Mario"],["dc.contributor.author","Heinemann, Uta"],["dc.contributor.author","Varges, Daniel. A."],["dc.contributor.author","Kretzschmar, Hans A."],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T09:17:31Z"],["dc.date.available","2018-11-07T09:17:31Z"],["dc.date.issued","2006"],["dc.description.abstract","A typical clinical course and low sensitivity of established diagnostic tests are the main diagnostic problems in the MV2 subtype of sporadic Creutzfeldt-Jakob disease (sCJD). Clinical symptoms and signs, MRI, EEG and biochemical CSF markers were studied in 26 patients. Histological findings were semiquantitatively evaluated. Compared with typical sCJD, the disease duration was prolonged (median 12 months). Dementia, ataxia and psychiatric symptoms were present in all patients. Extrapyramidal signs were observed in 88%. T2-weighted MRI showed basal ganglia hyperintensities in 90%. Increased thalamic signal intensity was detected in 88% on diffusion-weighted MRI. Increased CSF tau-protein was found in 83%, and the 14-3-3 test was positive in 76%. The EEG revealed periodic sharp wave complexes in only two patients. Kuru plaques, severe thalamic and basal ganglia gliosis and spongiform changes, and neuronal loss in the pulvinar were the prominent histological features. At least one of the three diagnostic tests (MRI, tau- and 14-3-3 protein) supported the clinical diagnosis in all patients. MRI was the most sensitive of the diagnostic tests applied. Thalamic hyperintensities were observed unusually frequently. Prolonged disease duration, early and prominent psychiatric symptoms, absence of typical EEG, thalamic hyperintensities on MRI and relatively low 14-3-3 protein sensitivity may be suspicious for variant CJD. However, distinct sensory symptoms and young age at onset, which are often found in the latter, are not common in the MV2 subtype, and the pulvinar sign was observed in only one case."],["dc.identifier.doi","10.1093/brain/awl123"],["dc.identifier.isi","000240679700006"],["dc.identifier.pmid","16720682"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28191"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.title","Clinical findings and diagnostic tests in the MV2 subtype of sporadic CJD"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1710"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Neurophysiology"],["dc.bibliographiccitation.lastpage","1721"],["dc.bibliographiccitation.volume","83"],["dc.contributor.author","Schuchmann, S."],["dc.contributor.author","Luckermann, M."],["dc.contributor.author","Kulik, A."],["dc.contributor.author","Heinemann, U."],["dc.contributor.author","Ballanyi, K."],["dc.date.accessioned","2018-11-07T09:24:50Z"],["dc.date.available","2018-11-07T09:24:50Z"],["dc.date.issued","2000"],["dc.description.abstract","In hippocampal slices from rats, dialysis with rhodamine-123 (Rh-123) and/or fura-2 via the patch electrode allowed monitoring of mitochondrial potential (Delta Psi) changes and intracellular Ca2+ ([Ca2+](i)) of CA1 pyramidal neurons. Plasmalemmal depolarization to 0 mV caused a mean [Ca2+](i) rise of 300 nM and increased Rh-123 fluorescence signal (RFS) by less than or equal to 50% of control. The evoked RFS, indicating depolarization of Delta Psi, and the [Ca2+](i) transient were abolished by Ca2+-free superfusate or exposure of Ni2+/Cd2+. Simultaneous measurements of RFS and [Ca2+](i) showed that the kinetics of both the Ca2+ rise and recovery were considerably faster than those of the Delta Psi depolarization. The plasmalemmal Ca2+/H+ pump blocker eosin-B potentiated the peak of the depolarization-induced RFS and delayed recovery of both the RFS and [Ca2+](i) transient. Thus the Delta Psi depolarization due to plasmalemmal depolarization is related to mitochondrial Ca2+ sequestration secondary to Ca2+ influx through voltage-gated Ca2+ channels. CN- elevated [Ca2+](i) by <50 nM but increased RFS by 221% as a result of extensive depolarization of Delta Psi. Oligomycin decreased RFS by 52% without affecting [Ca2+](i). In the presence of oligomycin, CN- and p-trifluoromethoxy-phenylhydrazone (FCCP) elevated [Ca2+](i) by <50 nM and increased RFS by 285 and 290%, respectively. Accordingly, the metabolism-related Delta Psi changes are independent of [Ca2+](i). Imaging techniques revealed that evoked [Ca2+](i) rises are distributed uniformly over the soma and primary dendrites, whereas corresponding changes in RFS occur more localized in subregions within the soma. The results show that microfluorometric measurement of the relation between mitochondrial function and intracellular Ca2+ is feasible in whole cell recorded mammalian neurons in situ."],["dc.identifier.isi","000085951200050"],["dc.identifier.pmid","10712491"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29924"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Physiological Soc"],["dc.relation.issn","1522-1598"],["dc.relation.issn","0022-3077"],["dc.title","Ca2+- and metabolism-related changes of mitochondrial potential in voltage-clamped CA1 pyramidal neurons in situ"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","355"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Neurology"],["dc.bibliographiccitation.lastpage","363"],["dc.bibliographiccitation.volume","256"],["dc.contributor.author","Meissner, Bettina"],["dc.contributor.author","Kallenberg, Kai"],["dc.contributor.author","Sanchez-Juan, Pascual"],["dc.contributor.author","Ramljak, Sanja"],["dc.contributor.author","Krasnianski, Anna"],["dc.contributor.author","Heinemann, U."],["dc.contributor.author","Eigenbrod, Sabina"],["dc.contributor.author","Gelpi, Elena"],["dc.contributor.author","Barsic, B."],["dc.contributor.author","Kretzschmar, Hans A."],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Knauth, Michael"],["dc.contributor.author","Zerr, I."],["dc.date.accessioned","2018-11-07T08:32:16Z"],["dc.date.available","2018-11-07T08:32:16Z"],["dc.date.issued","2009"],["dc.description.abstract","Iatrogenic Creutzfeldt-Jakob disease (iCJD) is mainly associated with dura mater (DM) grafts and administration of human growth hormones (hGH). Data on disease course in DM-CJD are limited. We describe the clinical and diagnostic findings in this patient group with special emphasis on MRI signal alterations. Ten DM-CJD patients were studied for their clinical symptoms and diagnostic findings. The MRIs were evaluated for signal increase of the cortical and subcortical structures. DM-CJD patients had a median incubation time of 18 years and median disease duration of 7 months. The majority of patients were MM homozygous at codon 129 of the prion protein gene (PRNP) and presented with gait ataxia and psychiatric symptoms. No correlation between the graft site and the initial disease course was found. The MRI showed cortical and basal ganglia signal increase each in eight out of ten patients and thalamic hyperintensity in five out of ten cases. Of interest, patients with thalamic signal increase were homozygous for methionine. The MRI findings in DM-CJD largely resemble those seen in sporadic CJD, as the cortex and basal ganglia are mainly affected."],["dc.identifier.doi","10.1007/s00415-009-0026-z"],["dc.identifier.isi","000265732800008"],["dc.identifier.pmid","19159063"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6742"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17302"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","0340-5354"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","MRI and clinical syndrome in dura materrelated Creutzfeldt-Jakob disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2278"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","2287"],["dc.bibliographiccitation.volume","129"],["dc.contributor.author","Collins, S. J."],["dc.contributor.author","Sanchez-Juan, Pascual"],["dc.contributor.author","Masters, Colin L."],["dc.contributor.author","Klug, G. M."],["dc.contributor.author","van Duijn, Cornelia M."],["dc.contributor.author","Poleggi, Anna"],["dc.contributor.author","Pocchiari, Mauricio"],["dc.contributor.author","Almonti, S."],["dc.contributor.author","Cuadrado-Corrales, Natividad"],["dc.contributor.author","de Pedro-Cuesta, Jesus"],["dc.contributor.author","Budka, H."],["dc.contributor.author","Gelpi, Elena"],["dc.contributor.author","Glatzel, Markus"],["dc.contributor.author","Tolnay, M."],["dc.contributor.author","Hewer, E."],["dc.contributor.author","Zerr, I."],["dc.contributor.author","Heinemann, U."],["dc.contributor.author","Kretszchmar, Hans A."],["dc.contributor.author","Jansen, Gerard H."],["dc.contributor.author","Olsen, E."],["dc.contributor.author","Mitrova, Eva"],["dc.contributor.author","Alperovitch, Annick"],["dc.contributor.author","Brandel, J.-P."],["dc.contributor.author","Mackenzie, Jan"],["dc.contributor.author","Murray, K."],["dc.contributor.author","Will, Robert G."],["dc.date.accessioned","2018-11-07T09:17:29Z"],["dc.date.available","2018-11-07T09:17:29Z"],["dc.date.issued","2006"],["dc.description.abstract","To validate the provisional findings of a number of smaller studies and explore additional determinants of characteristic diagnostic investigation results across the entire clinical spectrum of sporadic Creutzfeldt-Jakob disease (CJD), an international collaborative study was undertaken comprising 2451 pathologically confirmed (definite) patients. We assessed the influence of age at disease onset, illness duration, prion protein gene (PRNP) codon 129 polymorphism (either methionine or valine) and molecular sub-type on the diagnostic sensitivity of EEG, cerebral MR1 and the CSIF 14-3-3 immunoassay. For EEG and CSF 14-3-3 protein detection, we also assessed the influence of the time point in a patient's illness at which the investigation was performed on the likelihood of a typical or positive result. Analysis included a large subset of patients (n = 743) in whom molecular sub-typing had been performed using a combination of the PRNP codon 129 polymorphism and the form of protease resistant prion protein [type 1 or 2 according to Parchi et al. (Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neural 1999; 46: 224-233.)] present in the brain. Findings for the whole group paralleled the subset with molecular sub-typing data available, showing that age at disease onset and disease duration were independent determinants of typical changes on EEG, while illness duration significantly influenced positive CSF 14-3-3 protein detection; changes on brain MRI were not influenced by either of these clinical parameters, but overall, imaging data were less complete and consequently conclusions are more tentative. In addition to age at disease onset and illness duration, molecular sub-type was re-affirmed as an important independent determinant of investigation results. In multivariate analyses that included molecular sub-type, time point of the investigation during a patient's illness was found not to influence the occurrence of a typical or positive EEG or CSF 14-3-3 protein result. A typical EEG was most often seen in MM I patients and was significantly less likely in the MV1, MV2 and VV2 sub-types, whereas VV2 patients had an increased likelihood of a typical brain MRI. Overall, the CSF 14-3-3 immunoassay was the most frequently positive investigation (88.1%) but performed significantly less well in the very uncommon MV2 and MM2 subtypes. Our findings confirm a number of determinants of principal investigation results in sporadic CJD and underscore the importance of recognizing these pre-test limitations before accepting the diagnosis excluded or confirmed. Combinations of investigations offer the best chance of detection, especially for the less common molecular sub-types such as MV2 and MM2."],["dc.identifier.doi","10.1093/brain/awl159"],["dc.identifier.isi","000240679700005"],["dc.identifier.pmid","16816392"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28180"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.title","Determinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt-Jakob disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Zerr, I."],["dc.contributor.author","Heinemann, U."],["dc.contributor.author","Varges, Daniel. A."],["dc.contributor.author","Stoeck, Katharina"],["dc.contributor.author","Bartl, Mario"],["dc.contributor.author","Otto, Markus"],["dc.date.accessioned","2018-11-07T10:47:51Z"],["dc.date.available","2018-11-07T10:47:51Z"],["dc.date.issued","2004"],["dc.format.extent","S462"],["dc.identifier.doi","10.1016/S0197-4580(04)81526-4"],["dc.identifier.isi","000223058701523"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/48061"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.publisher.place","New york"],["dc.relation.conference","9th International Conference on Alzheimers Disease and Related Disorders"],["dc.relation.eventlocation","Philadelphia, PA"],["dc.relation.issn","0197-4580"],["dc.title","Cerebrospinal fluid investigations in Creutzfeldt-Jakob disease"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","863"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Alzheimer s Disease"],["dc.bibliographiccitation.lastpage","873"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Meyne, Felix"],["dc.contributor.author","Gloeckner, Sara Friederike"],["dc.contributor.author","Ciesielczyk, Barbara"],["dc.contributor.author","Heinemann, Uta"],["dc.contributor.author","Krasnianski, Anna"],["dc.contributor.author","Meissner, Bettina"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T08:34:47Z"],["dc.date.available","2018-11-07T08:34:47Z"],["dc.date.issued","2009"],["dc.description.abstract","We performed a study on levels of the total prion protein (PrP) in humans affected by different neurological diseases and assessed the influence of several factors such as age, gender, and disease severity on the cerebrospinal fluid PrP levels. PrP-ELISA technique was used to analyze cerebrospinal fluid (CSF) samples. 293 CSF samples of patients with Creutzfeldt-Jakob disease (CJD), Alzheimer's disease, dementia with Lewy-bodies, Parkinson's disease, multiple sclerosis, cerebral ischemia, generalized epileptic seizures, and meningitis and encephalitis in comparison to controls were analyzed. We found a significant reduction of CSF PrP levels in patients suffering from all neurodegenerative disorders analyzed. This group exhibited mean PrP values of 164 ng/ml while non-neurodegenerative disorder patients and healthy controls showed PrP levels of 208 ng/ml and 226 ng/ml, respectively. CSF levels correlated with disease severity in CJD, Alzheimer's disease, and dementia with Lewy- bodies. The finding of decreased PrP levels in the CSF of patients not only with CJD but also in other neurodegenerative disorders is intriguing. Age-, gender-, and genetic-specific factors might be involved in the PrPc regulation."],["dc.identifier.doi","10.3233/JAD-2009-1110"],["dc.identifier.isi","000269629400014"],["dc.identifier.pmid","19542614"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17899"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Ios Press"],["dc.relation.issn","1387-2877"],["dc.title","Total Prion Protein Levels in the Cerebrospinal Fluid are Reduced in Patients with Various Neurological Disorders"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","170"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Prion"],["dc.bibliographiccitation.lastpage","178"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Dabaghian, Reza"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Heinemann, Uta"],["dc.contributor.author","Zanusso, Gianluigi"],["dc.date.accessioned","2018-11-07T11:10:48Z"],["dc.date.available","2018-11-07T11:10:48Z"],["dc.date.issued","2008"],["dc.description.abstract","Recent concern about the possible secondary spread of vCJD through blood transfusion and blood products has highlighted the need for a sensitive test for the identification of PrP(TSE/res) in clinical specimens collected in a non-invasive way. In addition, a more accurate estimate of the prevalence of pre-clinical vCJD in the population may be possible if there were a test that could be applied to easily available material such as urine. As a step towards this goal, the detection of putative PrPTSE/ res in the urine of CJD patients has been improved, based on Proteinase K digestion of samples and western blotting. The modified western blot uses concentrated urine as a starting material. After proteolytic treatment followed by electrophoresis and western blotting, membranes are incubated with an anti-PrP antibody conjugated directly with horseradish peroxidase. This study was conducted on urine samples of CJD and other neurodegenerative disease affected individuals. Proteinase K resistant high molecular weight proteins were detected, which are suggested to be a complex of urinary PrP and immunoglobulin proteins. Whether urine can be used as a diagnostic tool for the detection of PrP could not be answered in this study."],["dc.identifier.isi","000263913400007"],["dc.identifier.pmid","19263593"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53289"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Landes Bioscience"],["dc.relation.issn","1933-6896"],["dc.title","Detection of proteinase K resistant proteins in the urine of patients with Creutzfeldt-Jakob and other neurodegenerative diseases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1126"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","European Journal of Neurology"],["dc.bibliographiccitation.lastpage","1133"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Gmitterova, Karin"],["dc.contributor.author","Heinemann, U."],["dc.contributor.author","Krasnianski, Anna"],["dc.contributor.author","Gawinecka, Joanna"],["dc.contributor.author","Zerr, I."],["dc.date.accessioned","2018-11-07T10:13:56Z"],["dc.date.available","2018-11-07T10:13:56Z"],["dc.date.issued","2016"],["dc.description.abstract","Background and purpose: Cerebrospinal fluid (CSF) analysis supports the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) when applied within an adequate clinical context. A diagnostic potential has been attributed to CSF proteins such as 14-3-3, but also tau protein, phosphorylated tau (181P) (p-tau) protein, amyloid beta(1-42), S100B and neuron-specific enolase (NSE). There has been only limited information available about the contribution of CSF analysis in the differentiation of various molecular sCJD subtypes. Methods: The CSF levels of the aforementioned proteins from 73 sCJD patients with distinct molecular subtypes were determined. Results: Differences in tau values were significant amongst the homozygous patients (MM and VV genotype) compared to the heterozygous group (P = 0.07 and P = 0.02 respectively). Significantly higher CSF tau levels (P = 0.003) and NSE (P = 0.02) but lower p-tau/tau ratio (P = 0.01) were observed in MM1 compared to MM2 patients. The p-tau/tau ratio enabled the differentiation of MV genotype with higher levels in PrPsc type 2 (P = 0.04). Elevation of S100B (P < 0.001) and NSE (P = 0.03) was observed in VV2 compared to VV1 subtype. PRNP codon 129 genotype, PrPsc isotype, disease duration and clinical stage influenced the test sensitivity in all proteins. Conclusions: Cerebrospinal fluid protein levels might be useful in the pre-mortem differentiation of molecular sCJD subtypes when the codon 129 genotype is known."],["dc.identifier.doi","10.1111/ene.12991"],["dc.identifier.isi","000375765000021"],["dc.identifier.pmid","27029507"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40525"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1468-1331"],["dc.relation.issn","1351-5101"],["dc.title","Cerebrospinal fluid markers in the differentiation of molecular subtypes of sporadic Creutzfeldt-Jakob disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","654"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Neurology Neurosurgery & Psychiatry"],["dc.bibliographiccitation.lastpage","659"],["dc.bibliographiccitation.volume","85"],["dc.contributor.author","Krasnianski, Anna"],["dc.contributor.author","Juan, P. Sanchez"],["dc.contributor.author","Ponto, Claudia"],["dc.contributor.author","Bartl, Mario"],["dc.contributor.author","Heinemann, U."],["dc.contributor.author","Varges, Daniel. A."],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Kretzschmar, Hans A."],["dc.contributor.author","Zerr, I."],["dc.date.accessioned","2018-11-07T09:39:44Z"],["dc.date.available","2018-11-07T09:39:44Z"],["dc.date.issued","2014"],["dc.description.abstract","Background In absence of a positive family history, the diagnosis of fatal familial insomnia (FFI) might be difficult because of atypical clinical features and low sensitivity of diagnostic tests. FFI patients usually do not fulfil the established classification criteria for Creutzfeldt-Jakob disease (CJD); therefore, a prion disease is not always suspected. Objective To propose an update of diagnostic pathway for the identification of patients for the analysis of D178-M129 mutation. Design and methods Data on 41 German FFI patients were analysed. Clinical symptoms and signs, MRI, PET, SPECT, polysomnography, EEG and cerebrospinal fluid biomarkers were studied. Results An algorithm was developed which correctly identified at least 81% of patients with the FFI diagnosis during early disease stages. It is based on the detection of organic sleep disturbances, either verified clinically or by a polysomnography, and a combination of vegetative and focal neurological signs and symptoms. Specificity of the approach was tested on three cohorts of patients (MM1 sporadic CJD patients, non-selected sporadic CJD and other neurodegenerative diseases). Conclusions The proposed scheme may help to improve the clinical diagnosis of FFI. As the sensitivity of all diagnostic tests investigated but polysomnography is low in FFI, detailed clinical investigation is of special importance."],["dc.identifier.doi","10.1136/jnnp-2013-305978"],["dc.identifier.isi","000336124400015"],["dc.identifier.pmid","24249784"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10971"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33354"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Bmj Publishing Group"],["dc.relation.issn","1468-330X"],["dc.relation.issn","0022-3050"],["dc.rights","CC BY-NC 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/3.0"],["dc.title","A proposal of new diagnostic pathway for fatal familial insomnia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","150"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","The Lancet Neurology"],["dc.bibliographiccitation.lastpage","158"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Haik, Stephane"],["dc.contributor.author","Marcon, Gabriella"],["dc.contributor.author","Mallet, Alain"],["dc.contributor.author","Tettamanti, Mauro"],["dc.contributor.author","Welaratne, Arlette"],["dc.contributor.author","Giaccone, Giorgio"],["dc.contributor.author","Azimi, Shohreh"],["dc.contributor.author","Pietrini, Vladimir"],["dc.contributor.author","Fabreguettes, Jean-Roch"],["dc.contributor.author","Imperiale, Daniele"],["dc.contributor.author","Cesaro, Pierre"],["dc.contributor.author","Buffa, Carlo"],["dc.contributor.author","Aucan, Christophe"],["dc.contributor.author","Lucca, Ugo"],["dc.contributor.author","Peckeu, Laurene"],["dc.contributor.author","Suardi, Silvia"],["dc.contributor.author","Tranchant, Christine"],["dc.contributor.author","Zerr, Ingo"],["dc.contributor.author","Houillier, Caroline"],["dc.contributor.author","Redaelli, Veronica"],["dc.contributor.author","Vespignani, Herve"],["dc.contributor.author","Campanella, Angela"],["dc.contributor.author","Sellal, Francois"],["dc.contributor.author","Krasnianski, Anna"],["dc.contributor.author","Seilhean, Danielle"],["dc.contributor.author","Heinemann, Uta"],["dc.contributor.author","Sedel, Frederic"],["dc.contributor.author","Canovi, Mara"],["dc.contributor.author","Gobbi, Marco"],["dc.contributor.author","Di Fede, Giuseppe"],["dc.contributor.author","Laplanche, Jean-Louis"],["dc.contributor.author","Pocchiari, Maurizio"],["dc.contributor.author","Salmona, Mario"],["dc.contributor.author","Forloni, Gianluigi"],["dc.contributor.author","Brandel, Jean-Philippe"],["dc.contributor.author","Tagliavini, Fabrizio"],["dc.date.accessioned","2018-11-07T09:44:35Z"],["dc.date.available","2018-11-07T09:44:35Z"],["dc.date.issued","2014"],["dc.description.abstract","Background Creutzfeldt-Jakob disease (CJD) is a fatal, untreatable prion encephalopathy. Previous studies showed that doxycycline is effective in in-vitro and in-vivo models of disease, and patients with CJD who received compassionate treatment with doxycycline showed increased survival time compared with historical series. We therefore did a randomised, double-blind study of doxycycline versus placebo in CJD. Methods We recruited patients older than 18 years old who had a diagnosis of definite or probable sporadic CJD or genetic forms of the disease via Italian reference centres and the French national referral system. Patients were randomly assigned (ratio 1:1) to receive oral doxycydine (100 mg daily) or placebo under double-blind conditions from the day of randomisation to death. Centralised randomisation was done independently of enrolment or evaluation of patients using a minimisation method in Italy and a simple randomisation in France. Participants, caregivers, and clinicians were masked to group assignment. The primary efficacy variable was the survival time from randomisation. Interim analyses were planned to detect a significant effect of treatment as early as possible. This trial is registered with EudraCT, 2006-001858-27 for the Italian study and 2007-005553-34 for the French study. Findings From April 12, 2007, to Aug 19, 2010, in Italy, and from Jan 30, 2009, to Jan 10, 2012, in France, 121 patients with CID were enrolled in the study, 62 of whom were randomly assigned to the treatment group and 59 to the placebo group. The first interim analysis showed absence of superiority of doxycycline compared with placebo, and the trial was stopped for futility. Efficacy analyses did not show significant differences between patients treated with doxycycline and placebo with regard to survival times (HR 1.1, 95% CI 0.8-1. 7, p=0.50). Serious adverse events were judged not to be related to treatment, whereas a relation was deemed probable or possible for five non-serious adverse events that occurred in each treatment group. Interpretation Doxycycline at a dose of 100 mg per day was well tolerated but did not significantly affect the course of CJD, at variance with the results of previous observational studies. Our experience could be useful in the design of large multinational controlled trials of potential anti-prion molecules in this rare disease."],["dc.identifier.doi","10.1016/S1474-4422(13)70307-7"],["dc.identifier.isi","000330546200010"],["dc.identifier.pmid","24411709"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34428"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","1474-4465"],["dc.relation.issn","1474-4422"],["dc.title","Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]