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Creutzfeldt–Jakob disease (CJD) is a rare and fatal neurodegenerative disorder with a worldwide incidence of 1–1.5 per million. As in other countries, a CJD surveillance unit with a clinical and neuropathological approach was established in Goettingen (Germany) in 1993. Here we report the epidemiological data from a prospective 12-year surveillance. Since 1993, there has been an increasing incidence of CJD, from 0.7 in 1993 to 1.6 in 2005 with a quite stable level since 1998. During this period, the proportion of patients with MV and VV codon 129 genotype rose, possibly because of better identification of atypical subtypes. Six percent of all patients had a PRNP mutation, mainly D178N-129M (FFI), E200K and V210I. Iatrogenic CJD was a rare phenomenon. No patient infected by cadaveric growth hormone extracts was reported. Furthermore, no variant CJD patient has yet been identified in Germany. Differential diagnoses revealed a variety of neurodegenerative diseases, with Alzheimers disease in the lead. One-third of the non-CJD patients included in this study suffered from a potentially treatable disorder such as metabolic or inflammatory diseases. The incidence and mortality rates in Germany are similar to those in other European countries. In contrast, however, acquired forms, such as iatrogenic and variant CJD are still rare in Germany or have not yet been identified. [ABSTRACT FROM AUTHOR]

Background: Data on impact of COVID-19 vaccination and outcomes of patients with COVID-19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience., Methods and Results: This was a retrospective analysis of patients with COVID-19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID-19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients; P =0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group ( P =0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome ( P =0.957). However, acute COVID-19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007-1.417]; P =0.041)., Conclusions: Our study demonstrated no impact of COVID-19 vaccination on angiographic or clinical outcome of COVID-19-positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID-19 was confirmed.

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Background: Data on the frequency and outcome of mechanical thrombectomy (MT) for large vessel occlusion (LVO) in patients with COVID-19 is limited. Addressing this subject, we report our multicenter experience., Methods: A retrospective cohort study was performed of consecutive acute stroke patients with COVID-19 infection treated with MT at 26 tertiary care centers between January 2020 and November 2021. Baseline demographics, angiographic outcome and clinical outcome evaluated by the modified Rankin Scale (mRS) at discharge and 90 days were noted., Results: We identified 111 out of 11 365 (1%) patients with acute or subsided COVID-19 infection who underwent MT due to LVO. Cardioembolic events were the most common etiology for LVO (38.7%). Median baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score were 16 (IQR 11.5-20) and 9 (IQR 7-10), respectively. Successful reperfusion (mTICI ≥2b) was achieved in 97/111 (87.4%) patients and 46/111 (41.4%) patients were reperfused completely. The procedure-related complication rate was 12.6% (14/111). Functional independence was achieved in 20/108 (18.5%) patients at discharge and 14/66 (21.2%) at 90 days follow-up. The in-hospital mortality rate was 30.6% (33/108). In the subgroup analysis, patients with severe acute COVID-19 infection requiring intubation had a mortality rate twice as high as patients with mild or moderate acute COVID-19 infection. Acute respiratory failure requiring ventilation and time interval from symptom onset to groin puncture were independent predictors for an unfavorable outcome in a logistic regression analysis., Conclusion: Our study showed a poor clinical outcome and high mortality, especially in patients with severe acute COVID-19 infection undergoing MT due to LVO., Competing Interests: Competing interests: MM: Grants or contracts from Balt, Medtronic, MircroVention and Stryker. FD: Consultant for Balt, Cerus Endovascular, Phenox and Cerenovus, honoraria for lectures from Cerenovus, Acandis and Asahi, support for attending meetings from MicroVention, Acandis and Cerus Endovascular, advisory board member for Cerenovus/Johnson & Johnson, associate editor for Journal of NeuroInterventional Surgery. MG: Grants or contracts from Else Kröner Fresenius Stiftung, payment of honoraria for lectures from Phenox, proctoring contract with MircroVention, participation on clinical event committee from MicroVention, chair of ESMINT Examination Committee, received stents from Phenox for research purposes. DK: Grants or contracts from Else Kröner Fresenius Center of Digital Health and Joachim Herz Foundation, spokesman of the “Junge Neuroradiologie” in the German Society of Neuroradiology. CL: Consulting fees, payment of honoraria for lectures and support for attending meetings from Phenox, Penumbra and Acandis. MW: Grants from ab medica, Acandis, Bracco Imaging, Cerenovus, Kaneka Pharmaceuticals, Medtronic, Mentice AB, Microvention, Phenox, Siemens Healthcare and Stryker Neurovascular; Consulting fees from Stryker Healthcare; Payment honoraria for lectures from Stryker Neurovascular. The other authors declare no specific conflict of interest., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Many health care professionals have to make morally difficult decisions during acute, stressful situations. The aim was to explore the applicability of an existing qualitatively developed model of individual reactions among professional first responders following such situations using a quantitative approach. According to the model, the interaction of antecedent individual and contextual characteristics affect the immediate emotional reactions to acute, stressful events involving a moral dilemma. Continuous coping efforts and the quality of social support will also affect the long-term positive and negative reactions to the event. The participants (n = 204, about 50% response rate) represented three Swedish health care professions stationed at a university hospital and a regional hospital: Physicians (n = 50), nurses (n = 94) and "others" (n =60, mainly social welfare officers and assistant nurses). Except for the personality dimension emotional stability which was measured using an established instrument, all measurement scales were operationalizations of codes and categories from the qualitative study (ten scales altogether). Four multiple regression analyses were performed with long-term positive and negative reactions in everyday acute and morally extremely taxing situations respectively as dependent variables. The outcome showed that long-term positive reactions covaried with much use of the coping strategies Emotional distancing and Constructive emotional confrontation and a perception of a well-functioning Formal social support. Regarding long-term negative reactions, higher age and little use of Emotional distancing accounted for much of the variance. Immediate emotional reactions also contributed significantly., Conclusion: the results largely supported the model concepts and their assumed relationships., (© 2018 Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

Purpose: Two recent randomized controlled trials (RCT) consistently showed superiority of aggressive medical treatment versus percutaneous transluminal angioplasty and stenting (PTAS) in patients with intracranial artery stenosis. Patients with symptomatic basilar stenosis have a higher long-term risk of recurrent stroke compared to patients with anterior circulation stenosis but no study has specifically focused on the role of PTAS in this subgroup. The aim of our study was to investigate the subgroup of patients with symptomatic basilar artery stenosis to find evidence for the feasibility of a future clinical trial., Methods: Patients with ischemic stroke caused by a symptomatic basilar stenosis and admitted to five German tertiary care hospitals were included in this multicenter effectiveness study. Primary outcome was a composite endpoint of stroke recurrence, clinically relevant restenosis, progression and death. Shared frailty Cox regression models were used to compare outcome rates between groups., Results: Of the 139 patients included in the study 79 (57 %) underwent PTAS and 60 (43 %) conservative treatment alone. The median follow-up period was 300 (IQR 18-738) days. Risks of the primary composite outcome (hazard ratio HR 0.49, 95 % confidence interval CI 0.25-0.97, p = 0.039) and of the key secondary outcomes recurrent stroke (HR 0.42, 95 % CI 0.19-0.95, p = 0.037) and clinically relevant restenosis/progression (HR 0.12, 95 % CI 0.03-0.59, p = 0.009) were lower in patients with PTAS compared to conservative treatment. There was no difference in all-cause mortality between groups (HR 0.98, 95 % CI 0.19-5.09, p = 0.979)., Conclusion: In this retrospective study we could not reproduce the findings from large RCTs on intracranial stenting. Our data could be considered as a basis for a prospective study on patient selection for PTAS in the basilar artery.

Background: There are contradictory reports concerning the validity of transcranial sonography (TCD and TCCS) for examinations of the basilar artery. Here we investigated sensitivity and specificity of transcranial sonography for the detection of basilar artery stenosis and in-stent-restenosis compared to cerebral angiography., Methods: We analyzed data of 104 examinations of the basilar artery. The association between sonographic peak systolic velocity (PSV) and degree of stenosis obtained by cerebral angiography was evaluated applying Spearman's correlation coefficient. Receiver Operating Characteristics (ROC) curves and areas under the curve (AUC) were calculated for the detection of a ≥50% stenosis defined by angiography. Optimal cut-off was derived using the Youden-index., Results: A weak but statistically significant correlation between PSV and the degree of stenosis was found (n=104, rho=0.35, p<0.001). ROC analysis for a detection of ≥50% stenosis showed an AUC of 0.70, a sensitivity of 74.0% and a specificity of 65.0% at the optimal cut off of 124 cm/s. Results were consistent when analyzing examinations done in stented and unstented arteries separately (TCD VS DSA/CTA in unstented artery: AUC=0.66, sensitivity 61.0%, specificity 65.0%, TCD/TCCS VS DSA in stented artery: AUC=0.63, sensitivity 71.0%, specificity 82.0%). Comparing TCCS measurements exclusively to angiography, ROC analysis showed an AUC of 1.00 for the detection of an in-stent-restenosis ≥50% with a sensitivity and specificity of 100% when a PSV of 132 cm/s was used as a cut off value., Conclusion: Validity of TCD in the assessment of basilar artery stenosis or in-stent restenosis is poor. First results for TCCS are promising, but due to the small samplesize further studies with larger samples sizes are warranted.

Background: Obstruction is a common cause of ventriculo-peritoneal shunt failure. Head computed tomography and plain x-ray examinations of shunt tubing ("shunt series") are routinely used in patients readmitted for reemerging symptoms but are of limited value. The validity of shunt series can be improved by applying contrast agent into the system (contrast-enhanced shunt series, a.k.a. a "shuntogram" or "shuntography"). We hypothesized that contrast-enhanced shunt series have a high predictive value for shunt revision surgeries., Methods: We retrospectively re-evaluated 107 contrast-enhanced shunt series and reviewed the patient histories. We defined outcome parameters for calculating the utility of a pathological contrast-enhanced shunt series in predicting revision surgery., Results: Of 107 contrast-enhanced shunt series, 41 examinations were positive for obstruction, mainly of the ventricular (36.5 %) and the peritoneal catheter (48.8 %). Within 30 days, 35 successful revision surgeries and 3 revision surgeries without resolution of symptoms were performed. In two cases the shunt tubing was found to be patent. Sixty-six negative examinations resulted in two revision surgeries, in addition to ten surgeries not attempting to restore patency. After 30 days, the specificity of contrast-enhanced shunt series for shunt failure identification was calculated at 92.8 %, the sensitivity at 94.7 %, the positive predictive value at 87.8 %, and the negative predictive value at 97.0 %., Conclusions: The contrast-enhanced shunt series method is a highly specific examination with a negative predictive value exceeding that of head computed tomography and plain shunt series. Compared to radionuclide marker studies, contrast-enhanced shunt series demonstrate better spatiotemporal resolution, enabling focused local surgical repair.

Background and Purpose Coil embolization of ruptured and unruptured aneurysms has emerged as a widely accepted alternative to clipping. Unfortunately, coil-embolized aneurysms need a long-term imaging follow-up to confirm the stability of the occlusion status. We investigated whether contrast-enhanced time-of-flight (ToF) magnetic resonance angiography (MRA) (gadolinium [Gd]-ToF) provides any diagnostic benefit over conventional ToF MRA (nonenhanced [NE]-ToF) in this context. Material and Methods From October 2013 to January 2015, all patients who were regularly scheduled for their follow-up after coil embolization were examined with Gd-ToF and NE-ToF angiography. The general visibility of the occlusion result was compared between the two MRAs as well as with the last digital subtraction angiography (DSA) available. Subgroups of interest (follow-up after stent-assisted coil embolization, cases with already known aneurysm remnants) were also analyzed. Results A total of 70 patients (44 female) harboring 74 treated aneurysms were examined. The reproducibility of the DSA result in terms of therapeutic relevance was 100%. In 10 of 74 cases (14%), the aneurysm status was more difficult to judge in the NE-ToF images (p = 0.02), and the visualization of small vessels was significantly better in the Gd-ToF (p = 0.003). NE-ToF did not fail to show any aneurysm remnants but were more difficult to depict in 35% of the cases (p = 0.09). Regarding the aneurysms that were coiled with stent assistance, there was no significant difference in terms of the visualization (p = 0.1). Conclusion Gd-ToF angiography is in general not superior to NE- ToF for the follow-up of coil-embolized aneurysms., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: The pharmaceutical therapy for acute ischemic stroke has shortcomings in reopening large vessels and dissolving long thrombi, and endovascular treatment has been found to provide added value. The Aperio thrombectomy device showed promising results in an experimental study. The purpose of this study was to evaluate the device clinically., Methods: 119 patients with acute stroke were treated in nine centers using the Aperio thrombectomy device. Target vessel, diameter, thrombus length, procedure time, recanalization, number of deployments, additional use of anticoagulants, complications, and the use of additional devices were assessed., Results: The median thrombus length was 15 mm (range 1.5-20 mm) and the average time from device insertion to recanalization was 30 min (range 5-120 min). Blood flow restoration (Thrombolysis In Cerebral Infarction (TICI) 2-3) was achieved in 85%. In the majority of cases complete clot removal was achieved (TICI 0, 12%; TICI 1, 2%; TICI 2a, 14%; TICI 2b, 18%; TICI 3, 53%). The median number of deployments was 2 (range 1-6). Twelve procedural complications (10%) occurred., Conclusions: The Aperio thrombectomy device seems to be an effective and adequately safe tool for reopening occluded cerebral arteries in the setting of acute stroke., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Gravitational valves (GVs) prevent overdrainage in ventriculoperitoneal shunting (VPS). However, there are no data available on the appropriate opening pressure in the shunt system when implementing a GV. We performed a retrospective analysis of hydrocephalic patients who were successfully treated with VPS which included one or more GV., Method: In this retrospective study in adult VPS patients with GVs, we analysed all available data, including the most recent computed tomography (CT) scans, to determine the best adjustments for alleviating any symptoms of overdrainage and underdrainage. Vertical effective opening pressure (VEOP) of the entire shunt system, including the differential pressure valve, was determined., Results: One hundred and twenty-two patients were eligible for the study. Of these, female patients revealed a higher VEOP compared with males (mean, 35.6 cmH2O [SD ± 2.46] vs 28.9 cmH2O [SD ± 0.87], respectively, p = 0.0072, t-test). In patients older than 60 years, lower VEOPs, by a mean of 6.76 cmH2O ± 2.37 (p = 0.0051), were necessary. Mean VEOP was found to be high in idiopathic intracranial hypertension (IIH; 41.6 cmH2O) and malresorptive and congenital HC (35.9 and 36.3), but low in normal pressure HC (27.5, p = 0.0229; one-way ANOVA). In the total cohort, body mass index (BMI) and height did not correlate with VEOP. Twelve patients required a VEOP of more than 40 cmH2O, and in eight of these patients this was accomplished by using multiple GVs. All but one of these eight patients were of female gender, and none of the latter were treated for normal pressure hydrocephalus (NPH) (p = 0.0044 and p = 0.0032, Fisher's exact test)., Conclusions: In adult VPS patients, female gender increases the risk of overdrainage requiring higher VEOPs. Initial implantation of adjustable GV should be considered in female patients treated with VP shunts for pathology other than NPH.

The authors report the case of a 76-year-old man with a spinal dural arteriovenous fistula. The patient suffered from sudden repeated reversible paraplegia after spinal digital subtraction angiography as well as CT angiography. Neurotoxicity of contrast media (CM) is the most probable cause for this repeated short-lasting paraplegia. Intolerance to toxicity of CM to the vulnerable spinal cord is rare, and probably depends on the individual patient. This phenomenon is transient and can occur after both intraarterial and intravenous CM application.

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.

Objectives: After suffering from severe acute respiratory distress syndrome, several patients show generalized brain alterations and atrophy. A distinctive morphologic pattern of cerebral injury, however, has not been found so far., Data Sources: We present the history of three patients who survived severe acute respiratory distress syndrome. In these patients, MRI of the brain showed multiple microhemorrhages predominantly in the splenium of the corpus callosum. An identical pattern of microhemorrhages has previously been described in mountaineers who suffered from high-altitude cerebral edema., Conclusions: This report demonstrates that patients after treatment for acute respiratory distress syndrome and high-altitude cerebral edema show congruent cerebral injuries. Further investigation into the similarities of the causative conditions and neurologic consequences might reveal underlying pathophysiologic mechanisms and clinical implications of this observation.

This meta-analysis summarizes the accuracy of magnetic resonance angiography (MRA) for diagnosing residuals in coiled cerebral aneurysms by using the threefold Roy classification (residuals: none, neck, or sac). Four databases were searched from 2000 to June 2013 for eligible studies that compared MRA to digital subtraction angiography (DSA) and reported 3 × 3 count data of threefold Roy classification, or a reduced scheme of 2 × 2 count data. Bivariate and trivariate Bayesian random-effects models were used for meta-analysis. Among 27 included studies (2,119 coiled aneurysms in 1,809 patients) the average prevalence of DSA-confirmed sac residuals was 18.2 % (range 0-43 %). The pooled sensitivity was 88.0 % (95 % CI 81.4-94.0) and specificity was 97.2 % (94.6-99.0 %) for assessing sac residuals by MRA. In the trivariate meta-analysis, a "sac residual" finding at MRA had a high positive likelihood ratio of 28.2 (14.0-79.0). A "neck residual" finding had a moderate negative likelihood ratio of 0.246 (0.111-0.426), and the MRA finding of "no residual" had a good negative likelihood ratio of 0.044 (0.013-0.096). Subgroup analyses identified no significant influence of covariates on diagnostic accuracy (P > 0.05). In conclusion, in coiled cerebral aneurysms MRA with application of the threefold Roy classification is well suited for detecting or excluding sac residuals that might require retreatment.

Introduction: Malignant brain tumors tend to migration and invasion of surrounding brain tissue. Histopathological studies reported malignant cells in macroscopically unsuspicious parenchyma (normal appearing white matter - NAWM) remote from the tumor localization. In early stages, diffuse interneural infiltration with changes of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) is hypothesized., Material and Methods: Patients' ADC and FA values from NAWM of the hemisphere contralateral to a malignant glioma were compared to age- and sex-matched normal controls., Results: Apparent diffusion coefficient levels of the entire contralateral hemisphere revealed a significant increase and a decrease of FA levels. An even more pronounced ADC increase was found in a region mirroring the glioma location., Conclusions: In patients with previously untreated anaplastic astrocytoma or glioblastoma, an increase of the ADC and a reduction of FA were found in the brain parenchyma of the hemisphere contralateral to the tumor localization. In the absence of visible MRI abnormalities, this may be an early indicator of microstructural changes of the NAWM attributed to malignant brain tumor.

Objective: Based on recent findings of microhemorrhages (MHs) in the corpus callosum (CC) in 3 individuals after nonfatal high-altitude cerebral edema (HACE), we hypothesized that hemosiderin depositions in the brain after high-altitude exposure are specific for HACE and remain detectable over many years., Methods: This was a cross-sectional study involving 37 mountaineers in 4 groups: 10 had experienced HACE, 8 high-altitude pulmonary edema, 11 severe acute mountain sickness, and 8 had climbed to altitudes ≥6,962 m without developing any high-altitude illness. HACE was defined as ataxia necessitating assistance with walking and/or decreased consciousness. Within <1 to 38 months after the qualifying incident, MRI of the brain was performed using a 3-tesla scanner and high-resolution susceptibility-weighted magnetic resonance sequences for detection of hemosiderin depositions, which were quantified by a score., Results: Unequivocal MHs located in the splenium of the CC were found in 8 subjects and questionable MHs were found in 2 subjects 1 to 35 months after HACE. They were located outside the CC in 5 more severe cases. MHs remained unchanged in those reexamined after 12 to 50 months. A few unequivocal MHs in the splenium of the CC were found in one subject after severe acute mountain sickness, while one subject with high-altitude pulmonary edema and 2 of the extreme altitude climbers had questionable lesions. In all other subjects, MHs were unequivocally absent., Conclusions: MHs detectable by susceptibility-weighted MRI predominantly in the splenium of the CC are long-lasting footprints of HACE.

Background and Purpose: Patient selection is crucial in the endovascular treatment of acute ischemic stroke patients. Baseline computed tomographic (CT) images, evaluated with the Alberta Stroke Program Early CT Scale (ASPECTS), are considered significant predictors of outcome. In this study, we evaluated CT images and perfusion parameters, analyzed with ASPECTS, as final outcome predictors after endovascular stroke treatment., Methods: We analyzed a cohort of patients with acute ischemic stroke and endovascular treatment. Patients with an occlusion of the M1 segment and multimodal CT imaging were included. CT perfusion data were reconstructed using commercial software. Two experienced neuroradiologists separately reviewed and scored CT and CT perfusion images with the ASPECTS score. Parameters were compared between patients with poor and with favorable follow-up outcome. Significantly different variables were further analyzed by forward stepwise logistic regression., Results: Fifty-one patients were included in our study. Baseline characteristics did not differ between patients with favorable and poor outcomes. No significant difference in recanalization status, the various times, or CT ASPECTS was demonstrated between these 2 groups. Significant differences were demonstrated for age (P=0.0049), cerebral blood volume ASPECTS (P=0.0007), and between cerebral blood volume and cerebral blood flow ASPECTS (P=0.0045). Cerebral blood volume ASPECTS>7 demonstrated the highest sensitivity and specificity for favorable outcome with 84% and 79%, respectively., Conclusions: CT perfusion parameters, evaluated with ASPECTS, are optimal predictors of outcome and are more sensitive and specific than CT ASPECTS in the prediction of favorable outcome. Use of these parameters in treatment decisions could reduce futile recanalizations.

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.