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1. Frailty is an outcome predictor in patients with acute ischemic stroke receiving endovascular treatment

Author

Arno Reich, Cornelius J. Werner, Martin Wiesmann, João Pinho, Charlotte Küppers, Jörg B. Schulz, and Omid Nikoubashman

Subjects
Aging, medicine.medical_specialty, Framingham Risk Score, Frailty, business.industry, Retrospective cohort study, General Medicine, Odds ratio, Logistic regression, Confidence interval, Brain Ischemia, Stroke, Treatment Outcome, Modified Rankin Scale, Interquartile range, Internal medicine, medicine, Humans, Geriatrics and Gerontology, business, Acute ischemic stroke, Aged, Ischemic Stroke, Retrospective Studies
Abstract

Introduction Frailty is a disorder of multiple physiological systems impairing the capacity of the organism to cope with insult or stress. It is associated with poor outcomes after acute illness. Our aim was to study the impact of frailty on the functional outcome of patients with acute ischemic stroke (AIS) submitted to endovascular stroke treatment (EST). Methods We performed a retrospective study of patients with AIS of the anterior circulation submitted to EST between 2012 and 2017, based on a prospectively collected local registry of consecutive patients. The Hospital Frailty Risk Score (HFRS) at discharge was calculated for each patient. We compared groups of patients with and without favourable 3-month outcome after index AIS (modified Rankin Scale 0–2 and 3–6, respectively). A multivariable logistic regression model was used to identify variables independently associated with favourable 3-month outcome. Diagnostic test statistics were used to compare HFRS with other prognostic scores for AIS. Results We included 489 patients with median age 75.6 years (interquartile range [IQR] = 65.3–82.3) and median NIHSS 15 (IQR = 11–19). About 29.7% presented a high frailty risk (HFRS >15 points). Patients with favourable 3-month outcome presented lower HFRS and lower prevalence of high frailty risk. High frailty risk was independently associated with decreased likelihood of favourable 3-month outcome (adjusted odds ratio = 0.48, 95% confidence interval = 0.26–0.89). Diagnostic performances of HFRS and other prognostic scores (THRIVE and PRE scores, SPAN-100 index) for outcome at 3-months were similar. Discussion Frailty is an independent predictor of outcome in AIS patients submitted to EST.

Published
2021

2. Standards bei der Anwendung der fiberendoskopischen Schluckuntersuchung in Deutschland

Author

A. Wehner, Bruno Fimm, B. Mall, Beate Schumann-Werner, and Cornelius J. Werner

Subjects
030507 speech-language pathology & audiology, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Neurology, business.industry, Medicine, Neurology (clinical), General Medicine, 0305 other medical science, business, 030217 neurology & neurosurgery
Abstract

Zusammenfassung Hintergrund Die fiberendoskopische Schluckuntersuchung („fiberoptic endoscopic evaluation of swallowing“, FEES) gilt als ein unverzichtbares instrumentelles Verfahren im Management schluckgestörter Patienten. Das eingeführte Ausbildungscurriculum hat das Ziel, die Qualitätsstandards zu erhöhen und zu einer Aufwertung des Verfahrens beizutragen. Fragestellung Die Studie untersucht, inwieweit eine standardisierte Durchführung, Auswertung und Dokumentation der FEES in Deutschland nach Einführung des Curriculums stattfindet. Material und Methoden Insgesamt 603 neurologische und geriatrische Kliniken in Deutschland wurden mithilfe eines Onlinefragebogens bezüglich struktureller Merkmale und deren Ablauf der Untersuchung befragt. Ergebnisse Insgesamt 190 Institutionen führten die Befragung vollständig durch. 43,31 % der Institutionen haben erst seit der Publikation des Curriculums die FEES implementiert. Die praktische Anwendung findet vermehrt durch Mediziner statt (59 %), das Schreiben des Befundes und die Kostempfehlung durch Logopäden (62 % und 83 %). Mit erhöhtem Ausbildungsgrad steigt die praktische Anwendung durch Logopäden. Die Durchführung weist trotz der Orientierung am Standardprotokoll nach Langmore besonders in Bezug auf die Durchführung der anatomisch-physiologischen Untersuchung, die verabreichten Konsistenzen und Nahrungsmittel und das Scoring schluckrelevanter Parameter Unterschiedlichkeiten auf. Diskussion Die Einführung des Curriculums hat zur Aufwertung der FEES und zu einer Stärkung der Logopädie als durchführende Berufsgruppe geführt. Zum jetzigen Stand liegt ein in wesentlichen Aspekten homogener Ablauf der Untersuchung vor, der jedoch Bedarf nach weiterer Vereinheitlichung zeigt. Das FEES-Curriculum könnte als Steuerungsinstrument zur weiteren Standardisierung verwendet werden.

Published
2021

3. H05 A joint initiative for improved care of huntington’s disease patients in Germany

Author

Gabriele Ritter, Michaela Winkelmann, Hannelore Ulrich, Cornelius J. Werner, Rena Overbeck, Kathrin Reetz, Christian Saß, Alzbeta Mühlbäck, Jochen Maier, Carsten Saft, Ines Reuter, Beate Schumann-Werner, Ralf Reilmann, Anne B, Michael Lang, Bernhard Landwehrmeyer, Anita Kretschmann, Jeanette Glasl, Bernhard U, and Carmen Vogel

Subjects
medicine.medical_specialty, Huntington's disease, Multidisciplinary approach, business.industry, Family medicine, medicine, In patient, Disease, medicine.disease, business, Patient organization, Working group, Intrathecal
Abstract

Background In Germany at least 8000 people suffer from clinically manifest HD, ultimately resulting in patients dependent on care. There are no defined pathways for multidisciplinary HD care in Germany. While slowing down the progression of HD may be available in the future, optimized care is needed now. Aims Jointly defined activities aim to provide a comprehensive multidisciplinary treatment concept covering all HD patients’ stations. Therefore, different stakeholders collaborate: patients, families, patient organization, various medical and therapeutic specialties as well as researchers. Methods In 2020 interdisciplinary advisory boards were initiated by Deutsche Huntington-Hilfe and Roche Pharma AG to identify the most urgent topics needing attention in HD. The following areas were identified and working groups with additional people in specific roles implemented: 1. Disease Awareness & Stigmatization, 2. Networking, 3. Multidisciplinary therapy, 4. Trainings, 5. Capacity for Intrathecal Injections, 6. Publication of a statement paper and 7. Development of a HD educational book for professionals. It is special and unique that all working group members are co-creating voluntarily because they all have the common purpose to improve HD families’ conditions. Outcome First results were the drafting of the ‘statement paper’, in which further recommendations for the multidisciplinary care approach in HD are defined, various disease awareness activities and publication of HD educational book for professionals. Conclusions The collaborative working groups completed first projects and further promising steps are on the way to improve the situation of HD families in Germany. Acknowledgment We thank Roche Pharma AG for their continued support of the described activities.

Published
2021

4. Introduction of a procedure to objectively quantify spastic movement impairment during freely performed voluntary movements

Author

Cornelius J. Werner, Anne-Kathrin Laßek, Catherine Disselhorst-Klug, and Sylvie Charlotte Anneliese Frieda von Werder

Subjects
medicine.medical_specialty, Movement, Biophysics, Neuroscience (miscellaneous), Brachioradialis, Context (language use), Electromyography, Biceps, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Elbow Joint, Elbow, Spastic, Humans, Medicine, Spasticity, Muscle, Skeletal, medicine.diagnostic_test, business.industry, Movement (music), Cerebral Palsy, Signal Processing, Computer-Assisted, Equipment Design, 030229 sport sciences, Biomechanical Phenomena, Stroke, Forearm, medicine.anatomical_structure, Muscle Spasticity, Arm, Upper limb, Neurology (clinical), medicine.symptom, business, Algorithms, 030217 neurology & neurosurgery
Abstract

Spastic impaired limb function is a frequent result of brain lesions. Although its assessment is important for clinical and therapeutical management, it still lacks an objective measure to quantify the functionality of the affected limb. The present paper reports a procedure based on the muscular activation recorded by Surface Electromyography (sEMG), which enables the assessment of the degree of spastic impairment. 15 healthy subjects and 7 patients with impaired upper limb function due to spasticity were included in the study. SEMG was recorded from the biceps and brachioradialis during active elbow extension at different movement velocities. The spastic impairment was clinically assessed by the Tardieu-Test and the Wolf Motor Function Test. Results of the clinical assessment and parameter values quantifying the muscular activation at different joint positions and movement velocities have been set in relation to one another. The results show that spastic impairment leads to a changed correlation between the muscular activation and movement velocity as well as to a changed inter-muscular co-ordination of biceps and brachioradialis. These changes, reflected in the sEMG, can be quantified by 5 newly introduced parameters. This way could allow the assessment of spastic impairment in the context of functional everyday tasks, for the first-time.

Published
2019

5. Medienunterstütztes Narrationstraining mit kontextreichen Fotos: Erprobung eines innovativen Ansatzes in der Aphasietherapie

Author

Katja Hußmann, Stefan Heim, Cornelius J. Werner, Kerstin I. Schattka, and Vera Leusch

Subjects
Gynecology, 030506 rehabilitation, 030507 speech-language pathology & audiology, 03 medical and health sciences, Psychiatry and Mental health, medicine.medical_specialty, Political science, medicine, 0305 other medical science, Applied Psychology
Abstract

Zusammenfassung Hintergrund In der autobiografischen Narration, dem Erzählen über sich selbst, kann Identitätsarbeit gelingen. Personen mit Aphasie (PMA) benötigen aufgrund der hohen linguistischen Komplexität Unterstützungsmaßnahmen innerhalb von narrativen Texten, die Narration im sozialen Austausch erleichtern bzw. ermöglichen. Methode In einem ersten Pilotprojekt im Rahmen einer Masterarbeit wurde eine narrativ ausgerichtete Intervention konzipiert und erprobt, in der PMA in Erzählsituationen über persönlich relevante Themen sog. Visual-Scene-Displays (VSD) mit kontextreichen Fotos am Smartphone einsetzen. Die Machbarkeit der Intervention wurde mit 2 PMA erprobt und der Mehrwert des Medieneinsatzes u. a. für den kommunikativen Austausch zwischen PMA und Gesprächspartnern anhand einer qualitativen und quantitativen Gesprächsanalyse untersucht. Ergebnisse Zwischen den Bedingungen mit vs. ohne VSD-Dateien-Nutzung zeigten sich vielfältige Unterschiede im Gesprächsverhalten, sowohl bei den PMA als auch ihren KommunikationspartnerInnen (KP). Beide Patienten initiierten bis zu 18 % mehr Äußerungen und mussten bis zu 18 % weniger auf Fragen antworten. Sie erlebten die Kommunikation subjektiv als positiver. Die KP stellten bis zu 40 % weniger Verständnisfragen. Sie kommentierten dafür bis zu 19 % mehr und gaben bis zu 18 % mehr positive Bestätigung. Das Verständnis i. S.v. „content units“ war erhöht. Auch die KP waren mit der Kommunikation subjektiv zufriedener. Diskussion Die Studie liefert damit einen neuen Ansatz zur logopädischen Versorgung bei Aphasie mit einer personenzentrierten und ressourcenorientierten Ausrichtung. Erste Ergebnisse bestätigen die Machbarkeit der Intervention sowie verschiedene positive Auswirkungen des hier beschriebenen Medieneinsatzes auf den kommunikativen Austausch über persönliche Themen. Eine Replikation mit größeren Stichproben ist notwendig.

Published
2018

6. Diagnosis and treatment of neurogenic dysphagia - S1 guideline of the German Society of Neurology

Author

Claus Wallesch, Cornelius J. Werner, Tobias Warnecke, Heidrun Schröter-Morasch, Helga Breitbach-Snowdon, Christian Ledl, Peter Pokieser, Jörg Bohlender, Klemens Fheodoroff, Christoph Lücking, Michaela Trapl-Grundschober, Ilia Aroyo, Christina Pflug, Rainer Wirth, Ulrike Beilenhoff, Gudrun Bartolome, Karl Hörmann, Johannes Weßling, Rainer Dziewas, Joerg C. Schefold, Roland Sparing, Kathi Schweikert, Jörg Glahn, Hans-Dieter Allescher, and Hans Jürgen Heppner

Subjects
medicine.medical_specialty, General Computer Science, Neuromuscular transmission, Neurosciences. Biological psychiatry. Neuropsychiatry, 610 Medicine & health, Guidelines, Aspiration pneumonia, 03 medical and health sciences, 0302 clinical medicine, Swallowing, medicine, otorhinolaryngologic diseases, Medical history, RC346-429, 030223 otorhinolaryngology, Intensive care medicine, business.industry, Swallowing Disorders, Guideline, medicine.disease, Dysphagia, Neurology. Diseases of the nervous system, Neurosurgery, medicine.symptom, business, 030217 neurology & neurosurgery, RC321-571
Abstract

Introduction Neurogenic dysphagia defines swallowing disorders caused by diseases of the central and peripheral nervous system, neuromuscular transmission, or muscles. Neurogenic dysphagia is one of the most common and at the same time most dangerous symptoms of many neurological diseases. Its most important sequelae include aspiration pneumonia, malnutrition and dehydration, and affected patients more often require long-term care and are exposed to an increased mortality. Based on a systematic pubmed research of related original papers, review articles, international guidelines and surveys about the diagnostics and treatment of neurogenic dysphagia, a consensus process was initiated, which included dysphagia experts from 27 medical societies. Recommendations This guideline consists of 53 recommendations covering in its first part the whole diagnostic spectrum from the dysphagia specific medical history, initial dysphagia screening and clinical assessment, to more refined instrumental procedures, such as flexible endoscopic evaluation of swallowing, the videofluoroscopic swallowing study and high-resolution manometry. In addition, specific clinical scenarios are captured, among others the management of patients with nasogastric and tracheotomy tubes. The second part of this guideline is dedicated to the treatment of neurogenic dysphagia. Apart from dietary interventions and behavioral swallowing treatment, interventions to improve oral hygiene, pharmacological treatment options, different modalities of neurostimulation as well as minimally invasive and surgical therapies are dealt with. Conclusions The diagnosis and treatment of neurogenic dysphagia is challenging and requires a joined effort of different medical professions. While the evidence supporting the implementation of dysphagia screening is rather convincing, further trials are needed to improve the quality of evidence for more refined methods of dysphagia diagnostics and, in particular, the different treatment options of neurogenic dysphagia. The present article is an abridged and translated version of the guideline recently published online (https://www.awmf.org/uploads/tx_szleitlinien/030-111l_Neurogene-Dysphagie_2020-05.pdf).

Published
2021

7. Clinical predictors and neural correlates for compromised swallowing safety in Huntington disease

Author

Rena Overbeck, Kathrin Reetz, Shahram Mirzazade, Bettina Mall, Beate Schumann-Werner, Imis Dogan, Cornelius J. Werner, Jörg B. Schulz, and Philipp Honrath

Subjects
medicine.medical_specialty, Aspiration pneumonia, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Physical medicine and rehabilitation, Huntington's disease, Swallowing, otorhinolaryngologic diseases, medicine, Humans, ddc:610, 030212 general & internal medicine, Gray Matter, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Voxel-based morphometry, medicine.disease, Magnetic Resonance Imaging, Dysphagia, Deglutition, Huntington Disease, Neurology, Female, Neurology (clinical), medicine.symptom, Deglutition Disorders, Speech-Language Pathology, business, 030217 neurology & neurosurgery
Abstract

European journal of neurology 28(9), 2855-2862 (2021). doi:10.1111/ene.14953, Published by Wiley-Blackwell, Oxford [u.a.]

Published
2021
Full Text
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8. AltersTraumaZentrum DGU®: Evaluation klinischer und ökonomischer Parameter

Author

Cornelius J. Werner, S. Poßelt, J.-P. Bach, H. J. Heppner, Leo Cornelius Bollheimer, M. Wollgarten, Mark Coburn, Matthias Knobe, Thomas Friess, B. Böttcher, B. Bücking, and C. Bliemel

Subjects
030222 orthopedics, Hip fracture, medicine.medical_specialty, business.industry, Standard treatment, 030208 emergency & critical care medicine, Context (language use), medicine.disease, Intensive care unit, law.invention, 03 medical and health sciences, 0302 clinical medicine, Geriatric trauma, law, Emergency medicine, Emergency Medicine, medicine, Orthopedics and Sports Medicine, Surgery, Decompensation, Myocardial infarction, Prospective cohort study, business
Abstract

BACKGROUND Previous studies on orthogeriatric models of care suggest that there is substantial variability in how geriatric care is integrated in the patient management and the necessary intensity of geriatric involvement is questionable. OBJECTIVE The aim of the current prospective cohort study was the clinical and economic evaluation of fragility fracture treatment pathways before and after the implementation of a geriatric trauma center in conformity with the guidelines of the German Trauma Society (DGU). METHODS A comparison of three different treatment models (6 months each) was performed: A: Standard treatment in Orthopaedic Trauma; B: Special care pathways with improvement of the quality management system and implementation of standard operating procedures; C: Interdisciplinary treatment with care pathways and collaboration with geriatricians (ward round model). RESULTS In the 151 examined patients (m/w 47/104; 83.5 (70-100) years; A: n = 64, B: n = 44, C: n = 43) pathways with orthogeriatric comanagement (C) improved frequency of postoperative mobilization (p = 0.021), frequency of osteoporosis prophylaxis (p = 0.001) and the discharge procedure (p = 0.024). In comparison to standard treatment (A), orthogeriatric comanagement (C) was associated with lower rates of mortality (9% vs. 2%; p = 0.147) and cardio-respiratory complications (39% vs. 28%; p = 0.235) by trend. In this context, there were low rates of myocardial infarction (6% vs. 0%), dehydration (6% vs. 0%), cardiac dysrhythmia (8% vs. 0%), pulmonary decompensation (28% vs. 16%), electrolyt dysbalance (34% vs. 19%) and pulmonary edema (11% vs. 2%). Duration of stay in an intensive care unit was 29 h (A) and 18 h (C) respectively (p = 0.205), with consecutive reduction in costs. A sole establishment of a special care pathway for older hip fracture patients (B) showed a lower rate of myocardial infarction (A: 11%, B: 0%, C: 0%; p = 0.035). CONCLUSION There was a clear tendency to a better overall result in patients receiving multidisciplinary orthogeriatric treatment using a ward visit model of orthogeriatric comanagement, with lower rates of cardiorespiratory complications and mortality. While special care pathways could reduce the rate of myocardial infarction in hip fracture patients, costs and revenues showed no difference between all care models evaluated. However, patients with hip fracture or periprosthetic fracture represent cohorts at clinical and economic risk as well.

Published
2018

9. Pharyngeal electrical stimulation for early decannulation in tracheotomised patients with neurogenic dysphagia after stroke (PHAST-TRAC): a prospective, single-blinded, randomised trial

Author

Rainer Dziewas, Rebecca Stellato, Ingeborg van der Tweel, Ernst Walther, Cornelius J Werner, Tobias Braun, Giuseppe Citerio, Mitja Jandl, Michael Friedrichs, Katja Nötzel, Milan R Vosko, Satish Mistry, Shaheen Hamdy, Susan McGowan, Tobias Warnecke, Paul Zwittag, Philip M Bath, Cornelius J. Werner, Milan Vosko, Ilia Aroyo, Christof Bucka, Thomas Kerz, Markus Köstenberger, Nicole Marschner-Preuth, Wolf-Dirk Niesen, Bettina Pfausler, Dziewas, R, Stellato, R, van der Tweel, I, Walther, E, Werner, C, Braun, T, Citerio, G, Jandl, M, Friedrichs, M, Nötzel, K, Vosko, M, Mistry, S, Hamdy, S, Mcgowan, S, Warnecke, T, Zwittag, P, Bath, P, Aroyo, I, Bucka, C, Kerz, T, Köstenberger, M, Marschner-Preuth, N, Niesen, W, and Pfausler, B

Subjects
Male, medicine.medical_treatment, Electric Stimulation Therapy, Stroke, dysphagia, randomized trial, Catheterization, 03 medical and health sciences, 0302 clinical medicine, Tracheotomy, Swallowing, Outcome Assessment, Health Care, Clinical endpoint, Humans, Medicine, Single-Blind Method, Prospective Studies, 030212 general & internal medicine, Adverse effect, Stroke, Aged, business.industry, Odds ratio, Middle Aged, medicine.disease, Dysphagia, Catheter, Anesthesia, Pharynx, Female, Neurology (clinical), medicine.symptom, Deglutition Disorders, business, 030217 neurology & neurosurgery
Abstract

Background Dysphagia after stroke is common, especially in severely affected, tracheotomised patients. In a pilot trial, pharyngeal electrical stimulation (PES) improved swallowing function in this group of patients. The PHAryngeal electrical STimulation for early decannulation in TRACheotomised stroke patients with neurogenic dysphagia trial (PHAST-TRAC) was designed to replicate and extend this single-centre experience. Methods Patients with recent stroke who required tracheotomy were randomised to receive three days of PES or sham. All patients had the stimulation catheter inserted; sham treatment was applied by connecting the base station to a simulator box instead of the catheter. Randomisation was done via a computerised interactive system with randomisation (stratified by site) in blocks of 4 patients per site. Patients and investigators applying PES were not masked. The primary-endpoint was assessed blinded to treatment assignment by a separate investigator at each site. The primary outcome was readiness for decannulation 24-72 hours post-treatment, assessed using fiberoptic endoscopic evaluation of swallowing and based on a standardised protocol including absence of massive saliva, presence of spontaneous swallows and laryngeal sensation. We planned a sequential statistical analysis of superiority for the primary endpoint. Interim analyses were to be performed after primary outcome data were available for 50 patients (futility), 70 patients, and every additional 10 patients thereafter up to 140. Analysis was by intention-to-treat. The trial was registered as ISRCTN18137204. Findings From 29th May 2015 to 5th July 2017, 69 patients (PES 35, sham 34) from 9 sites (7 acute care hospitals, 2 rehabilitation facilities) in Germany, Austria and Italy were included: PES group mean age 61.7 (SD 13.0) years, 8 (23%) patients with haemorrhagic stroke, median time onset to randomisation 28.0 [IQR 20, 49] days; sham group age 66.8 (10.3) years, 12 (35%) patients with haemorrhagic stroke, onset to randomisation 28.0 [18, 40] days). The Independent Data & Safety Monitoring Board recommended to stop the trial early for efficacy after 70 patients had been recruited and primary endpoint data of 69 patients were available. This decision was approved by the steering committee. PES was associated with more patients being ready for decannulation as compared to sham: 17 (49%) vs. 3 (9%), odds ratio (OR) 7.00 (2.41-19.88), p=0.00082). No patient required recannulation within 48 hours or during their documented follow-up period up to 30 days or hospital discharge. Adverse events (AEs) were reported in 24 patients (69%) of the PES group and 24 patients (71%) of the sham group. The number of patients with at least one serious adverse event (SAE) did not differ between the groups: 10 (29%) vs. 8 (23%), OR 1.3 (0.44-3.83), p=0.7851). 7 patients (20%) from the PES group and 3 patients (9%) from the sham group died during the study period. None of the patient deaths or SAEs reported were judged to be PES-treatment- or investigational device-related. Interpretation PES increased the proportion of patients with stroke and subsequent tracheotomy who were ready for decannulation in this study population, many of whom received PES within a month of their stroke. Future trials should confirm whether PES is beneficial in tracheostomised patients who receive stimulation similarly early after stroke and explore its effects in other cohorts.

Published
2018

10. Identification of genetic variants associated with Huntington's disease progression

Author

Davina J Hensman Moss, Antonio F Pardiñas, Douglas Langbehn, Kitty Lo, Blair R Leavitt, Raymund Roos, Alexandra Durr, Simon Mead, Peter Holmans, Lesley Jones, Sarah J Tabrizi, A Coleman, R Dar Santos, J Decolongon, A Sturrock, E Bardinet, C Jauff Ret, D Justo, S Lehericy, C Marelli, K Nigaud, R Valabrègue, SJA van den Bogaard, E M Dumas, J van der Grond, EP t'Hart, C Jurgens, M-N Witjes-Ane, N Arran, J Callaghan, C Stopford, C Frost, R Jones, N Hobbs, N Lahiri, R Ordidge, G Owen, T Pepple, J Read, M Say, E Wild, A Patel, N C Fox, C Gibbard, I Malone, H Crawford, D Whitehead, S Keenan, D M Cash, C Berna, N Bechtel, S Bohlen, A Hoff Man, P Kraus, E Axelson, C Wang, T Acharya, S Lee, W Monaco, C Campbell, S Queller, K Whitlock, M Campbell, E Frajman, C Milchman, A O'Regan, I Labuschagne, J Stout, B Landwehrmeyer, D Craufurd, R Scahill, S Hicks, C Kennard, H Johnson, A Tobin, HD Rosas, R Reilmann, B Borowsky, C Pourchot, S C Andrews, Anne-Catherine Bachoud-Lévi, Anna Rita Bentivoglio, Ida Biunno, Raphael Bonelli, Jean-Marc Burgunder, Stephen Dunnett, Joaquim Ferreira, Olivia Handley, Arvid Heiberg, Torsten Illmann, G. Bernhard Landwehrmeyer, Jamie Levey, Maria A. Ramos-Arroyo, Jørgen Nielsen, Susana Pro Koivisto, Markku Päivärinta, Raymund A.C. Roos, A Rojo Sebastián, Sarah Tabrizi, Wim Vandenberghe, Christine Verellen-Dumoulin, Tereza Uhrova, Jan Wahlström, Jacek Zaremba, Verena Baake, Katrin Barth, Monica Bascuñana Garde, Sabrina Betz, Reineke Bos, Jenny Callaghan, Adrien Come, Leonor Correia Guedes, Daniel Ecker, Ana Maria Finisterra, Ruth Fullam, Mette Gilling, Lena Gustafsson, Olivia J Handley, Carina Hvalstedt, Christine Held, Kerstin Koppers, Claudia Lamanna, Matilde Laurà, Asunción Martínez Descals, Saül Martinez-Horta, Tiago Mestre, Sara Minster, Daniela Monza, Lisanne Mütze, Martin Oehmen, Michael Orth, Hélène Padieu, Laurent Paterski, Nadia Peppa, Martina Di Renzo, Amandine Rialland, Niini Røren, Pavla Šašinková, Erika Timewell, Jenny Townhill, Patricia Trigo Cubillo, Wildson Vieira da Silva, Marleen R van Walsem, Carina Whalstedt, Marie-Noelle Witjes-Ané, Grzegorz Witkowski, Abigail Wright, Daniel Zielonka, Eugeniusz Zielonka, Paola Zinzi, Raphael M. Bonelli, Sabine Lilek, Karen Hecht, Brigitte Herranhof, Anna Holl, Hans-Peter Kapfhammer, Michael Koppitz, Markus Magnet, Nicole Müller, Daniela Otti, Annamaria Painold, Karin Reisinger, Monika Scheibl, Helmut Schöggl, Jasmin Ullah, Eva-Maria Braunwarth, Florian Brugger, Lisa Buratti, Eva-Maria Hametner, Caroline Hepperger, Christiane Holas, Anna Hotter, Anna Hussl, Christoph Müller, Werner Poewe, Klaus Seppi, Fabienne Sprenger, Gregor Wenning, Andrea Boogaerts, Godelinde Calmeyn, Isabelle Delvaux, Dirk Liessens, Nele Somers, Michel Dupuit, Cécile Minet, Dominique van Paemel, Pascale Ribaï, Dimphna van Reijen, Jirí Klempír, Veronika Majerová, Jan Roth, Irena Stárková, Lena E. Hjermind, Oda Jacobsen, Jørgen E. Nielsen, Ida Unmack Larsen, Tua Vinther-Jensen, Heli Hiivola, Hannele Hyppönen, Kirsti Martikainen, Katri Tuuha, Philippe Allain, Dominique Bonneau, Marie Bost, Bénédicte Gohier, Marie-Anne Guérid, Audrey Olivier, Adriana Prundean, Clarisse Scherer-Gagou, Christophe Verny, Blandine Babiloni, Sabrina Debruxelles, Charlotte Duché, Cyril Goizet, Laetitia Jameau, Danielle Lafoucrière, Umberto Spampinato, Rekha Barthélémy, Christelle De Bruycker, Maryline Cabaret Anne-Sophie Carette, Eric Decorte Luc Defebvre, Marie Delliaux, Arnaud Delval, Alain Destee, Kathy Dujardin, Marie-Hélène Lemaire, Sylvie Manouvrier, Mireille Peter, Lucie Plomhouse, Bernard Sablonnière, Clémence Simonin, Stéphanie Thibault-Tanchou, Isabelle Vuillaume, Marcellin Bellonet, Hassan Berrissoul, Stéphanie Blin, Françoise Courtin, Cécile Duru, Véronique Fasquel, Olivier Godefroy, Pierre Krystkowiak, Béatrice Mantaux, Martine Roussel, Sandrine Wannepain, Jean-Philippe Azulay, Marie Delfini, Alexandre Eusebio, Frédérique Fluchere, Laura Mundler, Mathieu Anheim, Celine Julié, Ouhaid Lagha Boukbiza, Nadine Longato, Gabrielle Rudolf, Christine Tranchant, Marie-Agathe Zimmermann, Christoph Michael Kosinski, Eva Milkereit, Daniela Probst, Kathrin Reetz, Christian Sass, Johannes Schiefer, Christiane Schlangen, Cornelius J. Werner, Harald Gelderblom, Josef Priller, Harald Prüß, Eike Jakob Spruth, Gisa Ellrichmann, Lennard Herrmann, Rainer Hoffmann, Barbara Kaminski, Peter Kotz, Christian Prehn, Carsten Saft, Herwig Lange, Robert Maiwald, Matthias Löhle, Antonia Maass, Simone Schmidt, Cecile Bosredon, Alexander Storch, Annett Wolz, Martin Wolz, Philipp Capetian, Johann Lambeck, Birgit Zucker, Kai Boelmans, Christos Ganos, Walburgis Heinicke, Ute Hidding, Jan Lewerenz, Alexander Münchau, Jenny Schmalfeld, Lars Stubbe, Simone Zittel, Gabriele Diercks, Dirk Dressler, Heike Gorzolla, Christoph Schrader, Pawel Tacik, Michael Ribbat, Bernhard Longinus, Katrin Bürk, Jens Carsten Möller, Ida Rissling, Mark Mühlau, Alexander Peinemann, Michael Städtler, Adolf Weindl, Juliane Winkelmann, Cornelia Ziegler, Natalie Bechtel, Heike Beckmann, Stefan Bohlen, Eva Hölzner, Ralf Reilmann, Stefanie Rohm, Silke Rumpf, Sigrun Schepers, Natalia Weber, Matthias Dose, Gabriele Leythäuser, Ralf Marquard, Tina Raab, Alexandra Wiedemann, Andrea Buck, Julia Connemann, Carolin Geitner, Andrea Kesse, Bernhard Landwehrmeyer, Christina Lang, Franziska Lezius, Solveig Nepper, Anke Niess, Ariane Schneider, Daniela Schwenk, Sigurd Süßmuth, Sonja Trautmann, Patrick Weydt, Claudia Cormio, Vittorio Sciruicchio, Claudia Serpino, Marina de Tommaso, Sabina Capellari, Pietro Cortelli, Roberto Galassi, Giovanni Rizzo, Roberto Poda, Cesa Scaglione, Elisabetta Bertini, Elena Ghelli, Andrea Ginestroni, Francesca Massaro, Claudia Mechi, Marco Paganini, Silvia Piacentini, Silvia Pradella, Anna Maria Romoli, Sandro Sorbi, Giovanni Abbruzzese, Monica Bandettini di Poggio, Giovanna Ferrandes, Paola Mandich, Roberta Marchese, Alberto Albanese, Daniela Di Bella, Anna Castaldo, Stefano Di Donato, Cinzia Gellera, Silvia Genitrini, Caterina Mariotti, Lorenzo Nanetti, Dominga Paridi, Paola Soliveri, Chiara Tomasello, Giuseppe De Michele, Luigi Di Maio, Marco Massarelli, Silvio Peluso, Alessandro Roca, Cinzia Valeria Russo, Elena Salvatore, Pierpaolo Sorrentino, Enrico Amico, Mariagrazia Favellato, Annamaria Griguoli, Irene Mazzante, Martina Petrollini, Ferdinando Squitieri, Barbara D'Alessio, Chiara Esposito, Rita Bentivoglio, Marina Frontali, Arianna Guidubaldi, Tamara Ialongo, Gioia Jacopini, Carla Piano, Silvia Romano, Francesco Soleti, Maria Spadaro, Monique S.E. van Hout, Marloes E. Verhoeven, Jeroen P.P. van Vugt, A. Marit de Weert, J.J.W. Bolwijn, M. Dekker, B. Kremer, K.L. Leenders, J.C.H. van Oostrom, Simon J.A. van den Bogaard, Eve M. Dumas, Ellen P. 't Hart, Berry Kremer, C.C.P. Verstappen, Olaf Aaserud, Jan Frich C, Ragnhild Wehus, Kathrine Bjørgo, Madeleine Fannemel, Per F. Gørvell, Eirin Lorentzen, Lars Retterstøl, Bodil Stokke, Inga Bjørnevoll, Sigrid Botne Sando, Artur Dziadkiewicz, Malgorzata Nowak, Piotr Robowski, Emilia Sitek, Jaroslaw Slawek, Witold Soltan, Michal Szinwelski, Magdalena Blaszcyk, Magdalena Boczarska-Jedynak, Ewelina Ciach-Wysocka, Agnieszka Gorzkowska, Barbara Jasinska-Myga, Gabriela Klodowska-Duda, Gregorz Opala, Daniel Stompel, Krzysztof Banaszkiewicz, Dorota Bocwinska, Kamila Bojakowska-Jaremek, Malgorzata Dec, Malgorzata Krawczyk, Monika Rudzinska, Elzbieta Szczygiel, Andrzej Szczudlik, Anna Wasielewska, Magdalena Wójcik, Anna Bryl, Anna Ciesielska, Aneta Klimberg, Jerzy Marcinkowski, Husam Samara, Justyna Sempolowicz, Anna Gogol, Piotr Janik, Hubert Kwiecinski, Zygmunt Jamrozik, Jakub Antczak, Katarzyna Jachinska, Wioletta Krysa, Maryla Rakowicz, Przemyslaw Richter, Rafal Rola, Danuta Ryglewicz, Halina Sienkiewicz-Jarosz, Iwona Stepniak, Anna Sulek, Elzbieta Zdzienicka, Karolina Zieora-Jakutowicz, Joaquim J Ferreira, Miguel Coelho, Tiago Mendes, Anabela Valadas, Carlos Andrade, Miguel Gago, Carolina Garrett, Maria Rosália Guerra, Carmen Durán Herrera, Patrocinio Moreno Garcia, Miquel Aguilar Barbera, Dolors Badenes Guia, Laura Casas Hernanz, Judit López Catena, Pilar Quiléz Ferrer, Ana Rojo Sebastián, Gemma Tome Carruesco, Jordi Bas, Núria Busquets, Matilde Calopa, Misericordia Floriach Robert, Celia Mareca Viladrich, Jesús Miguel Ruiz Idiago, Antonio Villa Riballo, Esther Cubo, Cecilia Gil Polo, Natividad Mariscal, Perez Jessica Rivadeneyra, Francisco Barrero, Blas Morales, María Fenollar, Rocío García-Ramos García, Paloma Ortega, Clara Villanueva, Javier Alegre, Mónica Bascuñana, Juan Garcia Caldentey, Marta Fatás Ventura, Guillermo García Ribas, Justo García de Yébenes, José Luis López-Sendón Moreno, Fernando Alonso Frech, Pedro J García Ruíz, Asunción Martínez-Descals, Rosa Guerrero, María José Saiz Artiga, Vicenta Sánchez, María Fuensanta Noguera Perea, Lorenza Fortuna, Salvadora Manzanares, Gema Reinante, María Martirio Antequera Torres, Laura Vivancos Moreau, Sonia González González, Luis Menéndez Guisasola, Carlos Salvador, Esther Suaréz San Martín, Inés Legarda Ramirez, Aranzazú Gorospe, Mónica Rodriguez Lopera, Penelope Navas Arques, María José Torres Rodríguez, Barbara Vives Pastor, Itziar Gaston, Maria Dolores Martinez-Jaurrieta, Jose Manuel Garcia Moreno, Carolina Mendez Lucena, Fatima Damas, Hermoso Eva Pacheco Cortegana, José Chacón Peña, Luis Redondo, Fátima Carrillo, María Teresa Cáceres, Pablo Mir, María José Lama Suarez, Laura Vargas-González, Maria E. Bosca, Francisco Castera Brugada, Juan Andres Burguera, Anabel Campos, Garcia Carmen Peiró Vilaplana, Peter Berglund, Radu Constantinescu, Gunnel Fredlund, Ulrika Høsterey-Ugander, Petra Linnsand, Liselotte Neleborn-Lingefjärd, Magnus Wentzel, Ghada Loutfi, Carina Olofsson, Eva-Lena Stattin, Laila Westman, Birgitta Wikström, Yanik Stebler, Alain Kaelin, Irene Romero, Michael Schüpbach, Sabine Weber Zaugg, Maria Hauer, Roman Gonzenbach, Hans H. Jung, Violeta Mihaylova, Jens Petersen, Roisin Jack, Kirsty Matheson, Zosia Miedzybrodzka, Daniela Rae, Sheila A Simpson, Fiona Summers, Alexandra Ure, Vivien Vaughan, Shahbana Akhtar, Jenny Crooks, Adrienne Curtis, Jenny de Souza, John Piedad, Hugh Rickards, Jan Wright, Elizabeth Coulthard, Louise Gethin, Beverley Hayward, Kasia Sieradzan, Matthew Armstrong, Roger A. Barker, Deidre O'Keefe, Anna Di Pietro, Kate Fisher, Anna Goodman, Susan Hill, Ann Kershaw, Sarah Mason, Nicole Paterson, Lucy Raymond, Rachel Swain, Natalie Valle Guzman, Monica Busse, Cynthia Butcher, Catherine Clenaghan, Sarah Hunt, Una Jones, Hanan Khalil, Michael Owen, Kathleen Price, Anne Rosser, Maureen Edwards, Carrie Ho, Teresa Hughes, Marie McGill, Pauline Pearson, Mary Porteous, Paul Smith, Peter Brockie, Jillian Foster, Nicola Johns, Sue McKenzie, Jean Rothery, Gareth Thomas, Shona Yates, Liz Burrows, Carol Chu, Amy Fletcher, Deena Gallantrae, Stephanie Hamer, Alison Harding, Stefan Klöppel, Alison Kraus, Fiona Laver, Monica Lewis, Mandy Longthorpe, Ivana Markova, Ashok Raman, Nicola Robertson, Mark Silva, Aileen Thomson, Sue Wild, Pam Yardumian, Carole Evans, Deena Gallentrae, Emma Hobson, Stuart Jamieson, Hannah Musgrave, Liz Rowett, Jean Toscano, Colin Bourne, Jackie Clapton, Carole Clayton, Heather Dipple, Dawn Freire-Patino, Janet Grant, Diana Gross, Caroline Hallam, Julia Middleton, Ann Murch, Catherine Thompson, Sundus Alusi, Rhys Davies, Kevin Foy, Emily Gerrans, Louise Pate, Thomasin Andrews, Andrew Dougherty, Charlotte Golding, Fred Kavalier, Hana Laing, Alison Lashwood, Dene Robertson, Deborah Ruddy, Alastair Santhouse, Anna Whaite, Stefania Bruno, Karen Doherty, Salman Haider, Davina Hensman, Nayana Lahiri, Marianne Novak, Aakta Patel, Elisabeth Rosser, Rachel Taylor, Thomas Warner, Edward Wild, Natalie Arran, Judith Bek, David Craufurd, Marianne Hare, Liz Howard, Susan Huson, Liz Johnson, Mary Jones, Helen Murphy, Emma Oughton, Lucy Partington-Jones, Dawn Rogers, Andrea Sollom, Julie Snowden, Cheryl Stopford, Jennifer Thompson, Iris Trender-Gerhard, Nichola Verstraelen, Leann Westmoreland, Richard Armstrong, Kathryn Dixon, Andrea H Nemeth, Gill Siuda, Ruth Valentine, David Harrison, Max Hughes, Andrew Parkinson, Beverley Soltysiak, Oliver Bandmann, Alyson Bradbury, Paul Gill, Helen Fairtlough, Kay Fillingham, Isabella Foustanos, Mbombe Kazoka, Kirsty O'Donovan, Cat Taylor, Katherine Tidswell, Oliver Quarrell, Puay Ngoh Lau, Emmanul Pica, Louis Tan, Univ Angers, Okina, Moss, Davina J. Hensman, Tabrizi, Sarah J, Mead, Simon, Kitty, Lo, Pardiã±as, Antonio F, Holmans, Peter, Jones, Lesley, Langbehn, Dougla, Coleman, A., Santos, R. Dar, Decolongon, J., Sturrock, A., Bardinet, E., Ret, C. Jauff, Justo, D., Lehericy, S., Marelli, C., Nigaud, K., Valabrãgue, R., van den Bogaard, S. J. A., Dumas, E. M., van der Grond, J., T'Hart, E. P., Jurgens, C., Witjes-Ane, M. -. N., Arran, N., Callaghan, J., Stopford, C., Frost, C., Jones, R., Hobbs, N., Lahiri, N., Ordidge, R., Owen, G., Pepple, T., Read, J., Say, M., Wild, E., Patel, A., Fox, N. C., Gibbard, C., Malone, I., Crawford, H., Whitehead, D., Keenan, S., Cash, D. M., Berna, C., Bechtel, N., Bohlen, S., Man, A. Hoff, Kraus, P., Axelson, E., Wang, C., Acharya, T., Lee, S., Monaco, W., Campbell, C., Queller, S., Whitlock, K., Campbell, M., Frajman, E., Milchman, C., O'Regan, A., Labuschagne, I., Stout, J., Landwehrmeyer, B., Craufurd, D., Scahill, R., Hicks, S., Kennard, C., Johnson, H., Tobin, A., Rosas, H. D., Reilmann, R., Borowsky, B., Pourchot, C., Andrews, S. C., Bachoud-Lévi, Anne-Catherine, Bentivoglio, Anna Rita, Biunno, Ida, Bonelli, Raphael, Burgunder, Jean-Marc, Dunnett, Stephen, Ferreira, Joaquim, Handley, Olivia, Heiberg, Arvid, Illmann, Torsten, Landwehrmeyer, G. Bernhard, Levey, Jamie, Ramos-Arroyo, Maria A., Nielsen, Jã¸rgen, Koivisto, Susana Pro, Pã¤ivã¤rinta, Markku, Roos, Raymund A. C., Sebastiã¡n, A. Rojo, Tabrizi, Sarah, Vandenberghe, Wim, Verellen-Dumoulin, Christine, Uhrova, Tereza, Wahlstrã¶m, Jan, Zaremba, Jacek, Baake, Verena, Barth, Katrin, Garde, Monica Bascuñana, Betz, Sabrina, Bos, Reineke, Callaghan, Jenny, Come, Adrien, Guedes, Leonor Correia, Ecker, Daniel, Finisterra, Ana Maria, Fullam, Ruth, Gilling, Mette, Gustafsson, Lena, Handley, Olivia J, Hvalstedt, Carina, Held, Christine, Koppers, Kerstin, Lamanna, Claudia, Laurã , Matilde, Descals, Asunción Martínez, Martinez-Horta, Saã¼l, Mestre, Tiago, Minster, Sara, Monza, Daniela, Mã¼tze, Lisanne, Oehmen, Martin, Orth, Michael, Padieu, Hã©lãne, Paterski, Laurent, Peppa, Nadia, Di Renzo, Martina, Rialland, Amandine, Rã¸ren, Niini, Å aå¡inkovã¡, Pavla, Timewell, Erika, Townhill, Jenny, Cubillo, Patricia Trigo, da Silva, Wildson Vieira, van Walsem, Marleen R, Whalstedt, Carina, Witjes-Ané, Marie-Noelle, Witkowski, Grzegorz, Wright, Abigail, Zielonka, Daniel, Zielonka, Eugeniusz, Zinzi, Paola, Bonelli, Raphael M., Lilek, 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Adriana, Scherer-Gagou, Clarisse, Verny, Christophe, Babiloni, Blandine, Debruxelles, Sabrina, Duchã©, Charlotte, Goizet, Cyril, Jameau, Laetitia, Lafoucriãre, Danielle, Spampinato, Umberto, Barthã©lã©my, Rekha, De Bruycker, Christelle, Carette, Maryline Cabaret Anne-Sophie, Defebvre, Eric Decorte Luc, Delliaux, Marie, Delval, Arnaud, Destee, Alain, Dujardin, Kathy, Lemaire, Marie-HélÃne, Manouvrier, Sylvie, Peter, Mireille, Plomhouse, Lucie, Sablonniãre, Bernard, Simonin, Clã©mence, Thibault-Tanchou, Stã©phanie, Vuillaume, Isabelle, Bellonet, Marcellin, Berrissoul, Hassan, Blin, Stã©phanie, Courtin, Franã§oise, Duru, Cã©cile, Fasquel, Vã©ronique, Godefroy, Olivier, Krystkowiak, Pierre, Mantaux, Bã©atrice, Roussel, Martine, Wannepain, Sandrine, Azulay, Jean-Philippe, Delfini, Marie, Eusebio, Alexandre, Fluchere, Frã©dã©rique, Mundler, Laura, Anheim, Mathieu, Juliã©, Celine, Boukbiza, Ouhaid Lagha, Longato, Nadine, Rudolf, Gabrielle, Tranchant, Christine, Zimmermann, Marie-Agathe, 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Natalie, Beckmann, Heike, Bohlen, Stefan, Hã¶lzner, Eva, Reilmann, Ralf, Rohm, Stefanie, Rumpf, Silke, Schepers, Sigrun, Weber, Natalia, Dose, Matthia, Leythã¤user, Gabriele, Marquard, Ralf, Raab, Tina, Wiedemann, Alexandra, Buck, Andrea, Connemann, Julia, Geitner, Carolin, Kesse, Andrea, Landwehrmeyer, Bernhard, Lang, Christina, Lezius, Franziska, Nepper, Solveig, Niess, Anke, Schneider, Ariane, Schwenk, Daniela, Sã¼ã muth, Sigurd, Trautmann, Sonja, Weydt, Patrick, Cormio, Claudia, Sciruicchio, Vittorio, Serpino, Claudia, de Tommaso, Marina, Capellari, Sabina, Cortelli, Pietro, Galassi, Roberto, Rizzo, Giovanni, Poda, Roberto, Scaglione, Cesa, Bertini, Elisabetta, Ghelli, Elena, Ginestroni, Andrea, Massaro, Francesca, Mechi, Claudia, Paganini, Marco, Piacentini, Silvia, Pradella, Silvia, Romoli, Anna Maria, Sorbi, Sandro, Abbruzzese, Giovanni, di Poggio, Monica Bandettini, Ferrandes, Giovanna, Mandich, Paola, Roberta, Marchese, Albanese, Alberto, Di Bella, Daniela, Castaldo, Anna, Di Donato, Stefano, Gellera, Cinzia, Genitrini, Silvia, Mariotti, Caterina, Nanetti, Lorenzo, Paridi, Dominga, Soliveri, Paola, Tomasello, Chiara, De Michele, Giuseppe, Di Maio, Luigi, Massarelli, Marco, Peluso, Silvio, Roca, Alessandro, Russo, Cinzia Valeria, Salvatore, Elena, Sorrentino, Pierpaolo, Amico, Enrico, Favellato, Mariagrazia, Griguoli, Annamaria, Mazzante, Irene, Petrollini, Martina, Squitieri, Ferdinando, D'Alessio, Barbara, Esposito, Chiara, Bentivoglio, Rita, Frontali, Marina, Guidubaldi, Arianna, Ialongo, Tamara, Jacopini, Gioia, Piano, Carla, Romano, Silvia, Soleti, Francesco, Spadaro, Maria, van Hout, Monique S. E., Verhoeven, Marloes E., van Vugt, Jeroen P. P., de Weert, A. Marit, Bolwijn, J. J. W., Dekker, M., Kremer, B., Leenders, K. L., van Oostrom, J. C. H., van den Bogaard, Simon J. A., Dumas, Eve M., â t Hart, Ellen P., Kremer, Berry, Verstappen, C. C. P., Aaserud, Olaf, Jan Frich, C., Wehus, Ragnhild, Bjã¸rgo, Kathrine, Fannemel, Madeleine, Gã¸rvell, Per F., Lorentzen, Eirin, Retterstã¸l, Lar, Stokke, Bodil, Bjã¸rnevoll, Inga, Sando, Sigrid Botne, Dziadkiewicz, Artur, Nowak, Malgorzata, Robowski, Piotr, Sitek, Emilia, Slawek, Jaroslaw, Soltan, Witold, Szinwelski, Michal, Blaszcyk, Magdalena, Boczarska-Jedynak, Magdalena, Ciach-Wysocka, Ewelina, Gorzkowska, Agnieszka, Jasinska-Myga, Barbara, Klodowska-Duda, Gabriela, Opala, Gregorz, Stompel, Daniel, Banaszkiewicz, Krzysztof, Bocwinska, Dorota, Bojakowska-Jaremek, Kamila, Dec, Malgorzata, Krawczyk, Malgorzata, Rudzinska, Monika, Szczygiel, Elzbieta, Szczudlik, Andrzej, Wasielewska, Anna, Wã³jcik, Magdalena, Bryl, Anna, Ciesielska, Anna, Klimberg, Aneta, Marcinkowski, Jerzy, Samara, Husam, Sempolowicz, Justyna, Gogol, Anna, Janik, Piotr, Kwiecinski, Hubert, Jamrozik, Zygmunt, Antczak, Jakub, Jachinska, Katarzyna, Krysa, Wioletta, Rakowicz, Maryla, Richter, Przemyslaw, Rola, Rafal, Ryglewicz, Danuta, Sienkiewicz-Jarosz, Halina, Stepniak, Iwona, Sulek, Anna, Zdzienicka, Elzbieta, Zieora-Jakutowicz, Karolina, Ferreira, Joaquim J, Coelho, Miguel, Mendes, Tiago, Valadas, Anabela, Andrade, Carlo, Gago, Miguel, Garrett, Carolina, Guerra, Maria Rosália, Herrera, Carmen Durán, Garcia, Patrocinio Moreno, Barbera, Miquel Aguilar, Guia, Dolors Badene, Hernanz, Laura Casa, Catena, Judit López, Ferrer, Pilar Quiléz, Sebastiã¡n, Ana Rojo, Carruesco, Gemma Tome, Bas, Jordi, Busquets, Nãºria, Calopa, Matilde, Robert, Misericordia Floriach, Viladrich, Celia Mareca, Idiago, Jesús Miguel Ruiz, Riballo, Antonio Villa, Cubo, Esther, Polo, Cecilia Gil, Mariscal, Natividad, Rivadeneyra, Perez Jessica, Barrero, Francisco, Morales, Bla, Fenollar, Marã­a, Garcã­a, Rocío García-Ramo, Ortega, Paloma, Villanueva, Clara, Alegre, Javier, Bascuã±ana, Mã³nica, Caldentey, Juan Garcia, Ventura, Marta Fatá, Ribas, Guillermo García, de Yébenes, Justo García, Moreno, José Luis López-Sendón, Frech, Fernando Alonso, Ruã­z, Pedro J. García, Martínez-Descals, Asunciã³n, Guerrero, Rosa, Artiga, María José Saiz, Sã¡nchez, Vicenta, Perea, María Fuensanta Noguera, Fortuna, Lorenza, Manzanares, Salvadora, Reinante, Gema, Torres, María Martirio Antequera, Moreau, Laura Vivanco, González González, Sonia, Guisasola, Luis Menéndez, Salvador, Carlo, Martã­n, Esther Suaréz San, Ramirez, Inés Legarda, Gorospe, Aranzazãº, Lopera, Mónica Rodriguez, Arques, Penelope Nava, Rodrã­guez, María José Torre, Pastor, Barbara Vive, Gaston, Itziar, Martinez-Jaurrieta, Maria Dolore, Moreno, Jose Manuel Garcia, Lucena, Carolina Mendez, Damas, Fatima, Cortegana, Hermoso Eva Pacheco, Peã±a, José Chacón, Redondo, Lui, Carrillo, Fã¡tima, Teresa Cáceres, Marã­a, Mir, Pablo, Suarez, María José Lama, Vargas-González, Laura, Bosca, Maria E., Brugada, Francisco Castera, Burguera, Juan Andre, Campos, Anabel, Vilaplana, Garcia Carmen Peiró, Berglund, Peter, Constantinescu, Radu, Fredlund, Gunnel, Høsterey-Ugander, Ulrika, Linnsand, Petra, Neleborn-Lingefjärd, Liselotte, Wentzel, Magnu, Loutfi, Ghada, Olofsson, Carina, Stattin, Eva-Lena, Westman, Laila, Wikstrã¶m, Birgitta, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schã¼pbach, Michael, Weber Zaugg, Sabine, Hauer, Maria, Gonzenbach, Roman, Jung, Hans H., Mihaylova, Violeta, Petersen, Jen, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, Simpson, Sheila A, Summers, Fiona, Ure, Alexandra, Vaughan, Vivien, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza, Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Armstrong, Matthew, Barker, Roger A., O'Keefe, Deidre, Di Pietro, Anna, Fisher, Kate, Goodman, Anna, Hill, Susan, Kershaw, Ann, Mason, Sarah, Paterson, Nicole, Raymond, Lucy, Swain, Rachel, Guzman, Natalie Valle, Busse, Monica, Butcher, Cynthia, Clenaghan, Catherine, Hunt, Sarah, Jones, Una, Khalil, Hanan, Owen, Michael, Price, Kathleen, Rosser, Anne, Edwards, Maureen, Carrie, Ho, Hughes, Teresa, Mcgill, Marie, Pearson, Pauline, Porteous, Mary, Smith, Paul, Brockie, Peter, Foster, Jillian, Johns, Nicola, Mckenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Burrows, Liz, Chu, Carol, Fletcher, Amy, Gallantrae, Deena, Hamer, Stephanie, Harding, Alison, Klã¶ppel, Stefan, Kraus, Alison, Laver, Fiona, Lewis, Monica, Longthorpe, Mandy, Markova, Ivana, Raman, Ashok, Robertson, Nicola, Silva, Mark, Thomson, Aileen, Wild, Sue, Yardumian, Pam, Evans, Carole, Gallentrae, Deena, Hobson, Emma, Jamieson, Stuart, Musgrave, Hannah, Rowett, Liz, Toscano, Jean, Bourne, Colin, Clapton, Jackie, Clayton, Carole, Dipple, Heather, Freire-Patino, Dawn, Grant, Janet, Gross, Diana, Hallam, Caroline, Middleton, Julia, Murch, Ann, Thompson, Catherine, Alusi, Sundu, Davies, Rhy, Foy, Kevin, Gerrans, Emily, Pate, Louise, Andrews, Thomasin, Dougherty, Andrew, Golding, Charlotte, Kavalier, Fred, Laing, Hana, Lashwood, Alison, Robertson, Dene, Ruddy, Deborah, Santhouse, Alastair, Whaite, Anna, Bruno, Stefania, Doherty, Karen, Haider, Salman, Hensman, Davina, Lahiri, Nayana, Novak, Marianne, Patel, Aakta, Rosser, Elisabeth, Taylor, Rachel, Warner, Thoma, Wild, Edward, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Rogers, Dawn, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iri, Verstraelen, Nichola, Westmoreland, Leann, Armstrong, Richard, Dixon, Kathryn, Nemeth, Andrea H, Siuda, Gill, Valentine, Ruth, David, Harrison, Hughes, Max, Parkinson, Andrew, Soltysiak, Beverley, Bandmann, Oliver, Bradbury, Alyson, Gill, Paul, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Kazoka, Mbombe, O'Donovan, Kirsty, Taylor, Cat, Tidswell, Katherine, Quarrell, Oliver, Lau, Puay Ngoh, Pica, Emmanul, Tan, Louis, Amsterdam Neuroscience - Neurodegeneration, Neurology, Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Moss, Davina J Hensman, Lo, Kitty, Pardiñas, Antonio F, Santos, R Dar, Ret, C Jauff, Valabrègue, R., Witjes-Ane, M. -N., Man, A Hoff, Bachoud-Lévi, Anne-Catherine, Nielsen, Jørgen, Päivärinta, Markku, Sebastián, A Rojo, Wahlström, Jan, Garde, Monica Bascuñana, Laurà, Matilde, Descals, Asunción Martínez, Martinez-Horta, Saül, Mütze, Lisanne, Padieu, Hélène, Røren, Niini, Šašinková, Pavla, Witjes-Ané, Marie-Noelle, Müller, Nicole, Schöggl, Helmut, Müller, Christoph, Minet, Cécile, Ribaï, Pascale, Klempír, Jirí, Majerová, Veronika, Stárková, Irena, Nielsen, Jørgen E., Hyppönen, Hannele, Gohier, Bénédicte, Guérid, Marie-Anne, Duché, Charlotte, Lafoucrière, Danielle, Barthélémy, Rekha, Lemaire, Marie-Hélène, Sablonnière, Bernard, Simonin, Clémence, Thibault-Tanchou, Stéphanie, Blin, Stéphanie, Courtin, Françoise, Duru, Cécile, Fasquel, Véronique, Mantaux, Béatrice, Fluchere, Frédérique, Julié, Celine, Prüß, Harald, Löhle, Matthia, Münchau, Alexander, Bürk, Katrin, Möller, Jens Carsten, Mühlau, Mark, Städtler, Michael, Hölzner, Eva, Leythäuser, Gabriele, Süßmuth, Sigurd, Marchese, Roberta, DI MAIO, Luigi, ’t Hart, Ellen P., Bjørgo, Kathrine, Gørvell, Per F., Retterstøl, Lar, Bjørnevoll, Inga, Wójcik, Magdalena, Guerra, Maria Rosália, Herrera, Carmen Durán, Catena, Judit López, Ferrer, Pilar Quiléz, Sebastián, Ana Rojo, Busquets, Núria, Idiago, Jesús Miguel Ruiz, Fenollar, María, García, Rocío García-Ramo, Bascuñana, Mónica, Ventura, Marta Fatá, Ribas, Guillermo García, de Yébenes, Justo García, Moreno, José Luis López-Sendón, Ruíz, Pedro J García, Martínez-Descals, Asunción, Artiga, María José Saiz, Sánchez, Vicenta, Perea, María Fuensanta Noguera, Torres, María Martirio Antequera, González González, Sonia, Guisasola, Luis Menéndez, Martín, Esther Suaréz San, Ramirez, Inés Legarda, Gorospe, Aranzazú, Lopera, Mónica Rodriguez, Rodríguez, María José Torre, Peña, José Chacón, Carrillo, Fátima, Teresa Cáceres, María, Suarez, María José Lama, Vargas-González, Laura, Vilaplana, Garcia Carmen Peiró, Høsterey-Ugander, Ulrika, Neleborn-Lingefjärd, Liselotte, Wikström, Birgitta, Schüpbach, Michael, Ho, Carrie, Klöppel, Stefan, Harrison, David, Cardiff University, University of Iowa [Iowa City], University of British Columbia (UBC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UCL, Institute of Neurology [London], National Oceanography Centre [Southampton] (NOC), University of Southampton, Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), IFR de Neuroimagerie Fonctionnelle (IFR 49), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), TRACK-HD investigators, Pardinas, Antonio F, Langbehn, Douglas, Lee, S Hong, TRACK-HD Investigators, and REGISTRY Investigators

Subjects
0301 basic medicine, Oncology, Registrie, Genome-wide association study, Longitudinal Studie, Disease, Bioinformatics, Severity of Illness Index, Principal Component Analysi, Longitudinal Studies, Registries, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Huntington disease, DNA-Binding Proteins, Settore MED/26 - NEUROLOGIA, Adult, Genome-Wide Association Study, Humans, Huntington Disease, MutS Homolog 3 Protein, Principal Component Analysis, Disease Progression, Neurology (clinical), huntingtin gene, age of onest, Huntington’s disease, Human, medicine.medical_specialty, cag repeat, instability, DNA-Binding Protein, Clinical Neurology, Principal component analysis, Single-nucleotide polymorphism, Biology, 03 medical and health sciences, Huntington's disease, Internal medicine, medicine, SNP, genome-wide association study, medicine.disease, R1, meta-analysis, Minor allele frequency, 030104 developmental biology, Age of onset, Trinucleotide repeat expansion, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation. Funding The European Commission FP7 NeurOmics project; CHDI Foundation; the Medical Research Council UK; the Brain Research Trust; and the Guarantors of Brain.

Published
2017

11. Welche Ursache haben unwillkürliche Spiegelbewegungen?

Author

Cornelius J. Werner, Manuel Dafotakis, Ferdinand Binkofski, Silvia Maaß, and Adrian Danek

Subjects
0301 basic medicine, Gynecology, 03 medical and health sciences, medicine.medical_specialty, 030104 developmental biology, 0302 clinical medicine, business.industry, Medicine, business, 030217 neurology & neurosurgery
Abstract

Bei Kindern treten Spiegelbewegungen physiologisch auf und sind wahrscheinlich der entwicklungsbedingten Unreife des Balkens geschuldet. Pathologische, angeborene Spiegelbewegungen konnen klinisch entweder isoliert oder als Teil komplexer genetischer Syndrome wie dem Kallmann-Syndrom und dem Klippel-Feil-Syndrom auftreten, kommen aber auch im Rahmen der infantilen Zerebralparese (Morbus Little) vor. Kongenitale isolierte Spiegelbewegungen folgen meist einem autosomal-dominanten Erbgang.

Published
2017

12. Safety and clinical impact of FEES – results of the FEES-registry

Author

Markus Perniß, R. Thomas, Juliane Dunkel, Cornelius J. Werner, Götz Bräuer, Beate Lindner-Pfleghar, Christian Ledl, Julia Schwarze, Michael Ohms, Hermann Weber, Sandra Hagen, Sriramya Lapa, Rainer Wirth, Ingo Wittich, Waltraud Pfeilschifter, Tanja Plass, Robin Roukens, Ulrich Vahle, Kathi Schweikert, Christine Helfer, Renate Damm-Lunau, Kolja Busch, Duygu Özsucu, Hartwig Woldag, Nancy Voigt, Nikolaus Lange, Tobias Warnecke, Christian L. Roth, Tobias Schmidt-Wilcke, Ulrich Birkmann, Christina Horn-Schenk, Sophie Held, Matthias auf dem Brinke, Hermann Neugebauer, Amelie Fellgiebel, Elisabeth Garms, Rainer Dziewas, Jörg Glahn, Madeleine Müller, Holger Stege, Mirko Hiller, Christoph Kley, Dirk Theuerkauf, Franziska Cerra, M. Mertl-Rötzer, and Beate Schumann

Subjects
medicine.medical_specialty, Neurology, business.industry, MEDLINE, medicine.disease, Dysphagia, lcsh:RC346-429, lcsh:RC321-571, Swallowing, Multicenter trial, Emergency medicine, medicine, Neurosurgery, medicine.symptom, business, Stroke, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Neuroradiology, Research Article
Abstract

Background At present, the flexible endoscopic evaluation of swallowing (FEES) is one of the most commonly used methods for the objective assessment of swallowing. This multicenter trial prospectively collected data on the safety of FEES and also assessed the impact of this procedure on clinical dysphagia management. Methods Patients were recruited in 23 hospitals in Germany and Switzerland from September 2014 to May 2017. Patient characteristics, professional affiliation of the FEES examiners (physicians or speech and language therapists), side-effects and cardiorespiratory parameters, severity of dysphagia and clinical consequences of FEES were documented. Results 2401 patients, mean age 69.8 (14.6) years, 42.3% women, were included in the FEES-registry. The most common main diagnosis was stroke (61%), followed by Parkinson’s disease (6.5%). FEES was well tolerated by patients. Complications were reported in 2% of examinations, were all self-limited and resolved without sequelae and showed no correlation to the endoscopist’s previous experience. In more than 50% of investigations FEES led to changes of feeding strategies, in the majority of cases an upgrade of oral diet was possible. Discussion This study confirmed that FEES, even when performed by less experienced clinicians is a safe and well tolerated procedure and significantly impacts on the patients’ clinical course. Implementation of a FEES-service in different clinical settings may improve dysphagia care. Trial registration ClinicalTrials.gov NCT03037762, registered January 31st 2017.

Published
2019

13. Ambulantes Dysphagiemanagement nach stationärem Aufenthalt

Author

Beate Schumann, Bettina Maring, Cornelius J. Werner, and Sarah Hemme

Subjects
Gynecology, medicine.medical_specialty, business.industry, medicine, General Medicine, business
Abstract

Auch wenn Dysphagien haufig vorkommen, werden sie oft nicht erkannt — mit zum Teil lebensbedrohlichen Folgen. Der Pflege kommt eine wichtige Rolle bei der Fruherkennung zu. Doch trotz Therapiebedarf sind viele Patienten mit chronischer Dysphagie logopadisch unterversorgt. Obwohl die Informationsweitergabe zwischen stationaren und ambulanten Behandlern meist luckenhaft ist, gibt es bereits einige gute Konzepte zur Verbesserung der Transparenz. Wunschenswert ist der Ausbau weiterer interdisziplinarer Dysphagie-Zentren in Deutschland.

Published
2017

14. Wenn das Schlucken gestört ist

Author

Cornelius J. Werner, Silja Kuckelkorn, Peter Dicks, and Beate Schumann

Subjects
Gynecology, medicine.medical_specialty, Philosophy, medicine
Abstract

Schon normale physiologische Alterungsprozesse beeinflussen die verschiedenen Phasen des Schluckens. Krankheitsbedingte Storungen verscharfen das Problem. Die wichtigste Regel fur den pflegerischen Umgang mit alten Menschen, die an Dysphagie leiden, ist ein hohes Mas an Aufmerksamkeit.

Published
2017

15. H32 Neuronal correlates and clinical predictors for dysphagia in huntington’s disease

Author

Cornelius J. Werner, Philipp Honrath, Imis Dogan, Patrick Weydt, Beate Schumann, Shahram Mirzazade, Kathrin Reetz, Rena Overbeck, and Falk Schradt

Subjects
medicine.medical_specialty, business.industry, Neuropsychology, Cognition, Voxel-based morphometry, Aspiration pneumonia, medicine.disease, Dysphagia, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Huntington's disease, Swallowing, Internal medicine, otorhinolaryngologic diseases, medicine, 030212 general & internal medicine, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Background Dysphagia is a common problem in HD, frequently leading to aspiration pneumonia and consecutive mortality. Objective estimates of prevalence using instrumental diagnostics and data on neuronal correlates of dysphagia in HD are scarce. Similarly, its correlation with other clinical markers is unknown. Thus, we aimed at defining clinical risk factors and neural correlated for HD-associated dysphagia more precisely. Methods/techniques 21 subjects (12 w, 9 m, Shoulson-Fahn stadium I-IV) underwent a full clinical-neurological exam including the UHDRS motor score and cognitive data from neuropsychological tests. A clinical swallowing examination was performed by a trained SLT, as well as videoendoscopic swallow examination (FEES). Patients additionally underwent an MRI scan (T1, 3 Tesla MRI Siemens Prisma). We then correlated validated scores of dysphagia with motor and cognitive scores as well as measures of atrophy from MRI. Results/outcome Mean UHDRS motor score was 33.6 (SD 15.3), mean UHDRS cognition score 158.6 (SD 64.3). In 20 patients, FEES showed penetration or aspiration in 80%. No significant correlations were found between dysphagia severity and any of the clinical markers (motor score, cognition, functional assessment, age, CAG). Voxel based morphometry confirmed atrophy patterns in known swallowing-network areas rather than motor function, e.g. striatum, when comparing patients with no/mild vs. moderate/severe dysphagia. Conclusions Our results so far suggest that dysphagia is not predicted sufficiently well by clinical markers, as aspiration can occur even in early stage of HD, thus necessitating early instrumental assessments in the course of the disease. Arguably, dysphagia should not be referred to as a ‘prevalent motor symptom’, but rather as a distinct entity.

Published
2018

16. Risk factors of suicidal ideation in Huntington's disease: literature review and data from Enroll-HD

Author

Cornelius J. Werner, Mikhail Votinov, Philipp Honrath, Raquel E. Gur, Bernhard Landwehrmeyer, Ute Habel, Jörg B. Schulz, Rena Overbeck, Imis Dogan, Kathrin Reetz, Katharina S. Görlich, Olga A. Wudarczyk, and Beate Schumann

Subjects
medicine.medical_specialty, Population, Disease, Irritability, Suicidal Ideation, 03 medical and health sciences, 0302 clinical medicine, Huntington's disease, Risk Factors, medicine, Humans, Apathy, Psychiatry, education, Suicidal ideation, Depression (differential diagnoses), education.field_of_study, business.industry, medicine.disease, 030227 psychiatry, Huntington Disease, Neurology, Anxiety, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Suicide is a leading cause of death in Huntington’s disease (HD), following pneumonia. Up to one-fifth of individuals with HD report suicidal ideation. Identifying the risk factors of suicidal ideation in this clinical population is thus pivotal. Here, we review the literature on prevalence rates and risk factors of suicidal ideation in premanifest and manifest patients and re-evaluate them using the largest currently existing clinical dataset from the ongoing observational study “Enroll-HD” (N = 5709). Large scale studies yielded important insights regarding suicidal ideation in HD. However, estimated prevalence rates vary among studies and risk factors are still poorly understood. According to the Enroll-HD data, pre- and manifest disease stages are associated with current (5.8–10%) and a history of suicidal ideation (18.6–30.9%). Throughout the course of HD, a history of suicidal ideation and the presence of depressive symptoms were strongly associated with current suicidal ideation. However, while for premanifest individuals, socio-demographics and activities of daily living appear to be important, in manifest patients, suicidal ideation is more closely linked to anxiety, irritability, psychosis, and apathy. These results highlight the importance of treating depressive symptoms in patients with HD and addressing potential suicidal ideation during clinical monitoring. The relevance of risk factors may differ among premanifest and manifest patients.

Published
2018

17. Response to 'Comments on mortality and cardiorespiratory complications in trochanteric femoral fractures: a ten year retrospective analysis'

Author

Cornelius J. Werner, Bong Sung Kim, Benjamin Bücking, Juliane Carow, Christopher Bliemel, Mark Coburn, Matthias Knobe, J.-P. Bach, Leo Cornelius Bollheimer, John Bennet Carow, University of Zurich, and Knobe, Matthias

Subjects
030222 orthopedics, medicine.medical_specialty, business.industry, Hip Fractures, General surgery, Cardiorespiratory fitness, 610 Medicine & health, Bone Nails, 2746 Surgery, 03 medical and health sciences, 0302 clinical medicine, 2732 Orthopedics and Sports Medicine, Orthopedic surgery, medicine, Retrospective analysis, Humans, Orthopedics and Sports Medicine, Surgery, 030212 general & internal medicine, business, 10266 Clinic for Reconstructive Surgery, Retrospective Studies
Published
2018

18. Resting-state connectivity in neurodegenerative disorders: Is there potential for an imaging biomarker?

Author

Kathrin Reetz, Cornelius J. Werner, and Christian Hohenfeld

Subjects
0301 basic medicine, Imaging biomarker, Cognitive Neuroscience, Rest, Disease, Review Article, Review, lcsh:Computer applications to medicine. Medical informatics, lcsh:RC346-429, Resting-state, 03 medical and health sciences, 0302 clinical medicine, Neural Pathways, medicine, Humans, Radiology, Nuclear Medicine and imaging, ddc:610, Neurodegeneration, lcsh:Neurology. Diseases of the nervous system, Default mode network, Brain Mapping, Resting state fMRI, business.industry, Dementia with Lewy bodies, fMRI, Neurodegenerative Diseases, Biomarker, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, Neurology, lcsh:R858-859.7, Biomarker (medicine), Neurology (clinical), business, Neuroscience, 030217 neurology & neurosurgery, Biomarkers, Frontotemporal dementia
Abstract

Biomarkers in whichever modality are tremendously important in diagnosing of disease, tracking disease progression and clinical trials. This applies in particular for disorders with a long disease course including pre-symptomatic stages, in which only subtle signs of clinical progression can be observed. Magnetic resonance imaging (MRI) biomarkers hold particular promise due to their relative ease of use, cost-effectiveness and non-invasivity. Studies measuring resting-state functional MR connectivity have become increasingly common during recent years and are well established in neuroscience and related fields. Its increasing application does of course also include clinical settings and therein neurodegenerative diseases. In the present review, we critically summarise the state of the literature on resting-state functional connectivity as measured with functional MRI in neurodegenerative disorders. In addition to an overview of the results, we briefly outline the methods applied to the concept of resting-state functional connectivity. While there are many different neurodegenerative disorders cumulatively affecting a substantial number of patients, for most of them studies on resting-state fMRI are lacking. Plentiful amounts of papers are available for Alzheimer's disease (AD) and Parkinson's disease (PD), but only few works being available for the less common neurodegenerative diseases. This allows some conclusions on the potential of resting-state fMRI acting as a biomarker for the aforementioned two diseases, but only tentative statements for the others. For AD, the literature contains a relatively strong consensus regarding an impairment of the connectivity of the default mode network compared to healthy individuals. However, for AD there is no considerable documentation on how that alteration develops longitudinally with the progression of the disease. For PD, the available research points towards alterations of connectivity mainly in limbic and motor related regions and networks, but drawing conclusions for PD has to be done with caution due to a relative heterogeneity of the disease. For rare neurodegenerative diseases, no clear conclusions can be drawn due to the few published results. Nevertheless, summarising available data points towards characteristic connectivity alterations in Huntington's disease, frontotemporal dementia, dementia with Lewy bodies, multiple systems atrophy and the spinocerebellar ataxias. Overall at this point in time, the data on AD are most promising towards the eventual use of resting-state fMRI as an imaging biomarker, although there remain issues such as reproducibility of results and a lack of data demonstrating longitudinal changes. Improved methods providing more precise classifications as well as resting-state network changes that are sensitive to disease progression or therapeutic intervention are highly desirable, before routine clinical use could eventually become a reality., Highlights • Review of literature on resting-state fMRI connectivity in neurodegeneration. • In diagnosing dementias resting-state fMRI bears potential to act as a biomarker. • Most neurodegenerative diseases show distinct altered networks across studies. • More studies and protocol harmonization will foster clinical resting-state fMRI.

Published
2018

19. Mortality and cardiorespiratory complications in trochanteric femoral fractures: a ten year retrospective analysis

Author

Juliane Carow, John Bennet Carow, Mark Coburn, B. Bücking, Matthias Knobe, Bong-Sung Kim, J.-P. Bach, Leo Cornelius Bollheimer, Christopher Bliemel, and Cornelius J. Werner

Subjects
Male, medicine.medical_specialty, Osteoporosis, Bone Screws, Bone Nails, law.invention, Intramedullary rod, 03 medical and health sciences, Fracture Fixation, Internal, 0302 clinical medicine, Postoperative Complications, law, Risk Factors, medicine, Humans, Minimally Invasive Surgical Procedures, Orthopedics and Sports Medicine, 030212 general & internal medicine, Hospital Mortality, Aged, Retrospective Studies, Aged, 80 and over, 030222 orthopedics, Hip fracture, business.industry, Hip Fractures, Incidence (epidemiology), Mortality rate, Incidence, Femoral fracture, Middle Aged, medicine.disease, Surgery, Logistic Models, Orthopedic surgery, Population study, Female, business
Abstract

Despite intense research and innovations in peri-operative management, a high mortality rate and frequent systemic complications in trochanteric femoral fractures persist. The aim of the present study was to identify predictive factors for mortality and cardio-respiratory complications after different treatment methods in a ten year period at a level I trauma centre. Retrospectively, all patients above 60 years of age with trochanteric femoral fracture between January 2000 and May 2011 were analyzed at a level I trauma centre. Demographic variables, comorbidities, and data regarding the surgical procedures, including required transfusions and post-operative complications, were evaluated, and the in-hospital mortality was recorded. The grade of osteoporosis was classified radiographically using the Singh index. The in-hospital mortality rate was 8.2% among 437 patients (male/female ratio = 110/327, mean age = 81 years) with extramedullary open (n = 144), intramedullary (n = 166), and extramedullary minimally invasive (n = 125) procedures. Significant influential factors on in-hospital mortality were identified with binary logistic regression analysis: an age of ≥90 years (P = 0.011), male sex (P = 0.003), a high American Society of Anesthesiologists (ASA) grade (3–5, P = 0.042), and a high osteoporosis grade (Singh index 3–1, P = 0.011). A total of 21.5% of the study population suffered cardio-respiratory complications post-operatively. The specific mortality was 28.7% (P

Published
2017

20. Altered resting-state connectivity in Huntington's Disease

Author

Cornelius J. Werner, Imis Dogan, N. Jon Shah, Shahram Mirzazade, Kathrin Reetz, Christian Saß, Jörg B. Schulz, and Johannes Schiefer

Subjects
Radiological and Ultrasound Technology, Resting state fMRI, Thalamus, Context (language use), Voxel-based morphometry, Striatum, computer.software_genre, medicine.disease, Neurology, Huntington's disease, Voxel, medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Anatomy, Psychology, computer, Neuroscience, Default mode network
Abstract

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Using resting-state fMRI (rs-fMRI) we investigated the functional integrity of resting-state networks (RSN) in HD. 17 HD and 19 matched control participants were examined at a 3 Tesla MR scanner. After controlling for structural degenera- tion by means of voxel-based morphometry, task-free rs-fMRI data were analyzed using Independent Component Analysis (ICA) and a dual-regression approach in the context of genetic and clinical parameters. Further, we evaluated HD-related differences in interregional connectivity between net- works. RSN analysis showed a significant increase in intrinsic functional connectivity in the HD sam- ple compared with controls, including the thalamus, striatum, prefrontal, premotor, and parietal maps. A subset of the Default Mode Network (DMN) was also affected. In the HD cohort, motor impairment correlated with higher network connectivity in mainly motor and parietal cortices. Deteriorating total functional capacity was additionally associated with higher connectivity in the striatum, thalamus, insular and frontal areas. This pattern of increased activity in intrinsic functional networks might sug- gest a reduced ability of intra-network differentiation with clinical disease progression in HD. Finally, results showed reduced long-range connectivity between parietal ICA components in HD compared to controls, indicating impaired functional coupling between interregional networks in HD. Our data demonstrates that functional connectivity is profoundly altered in HD, both within and between RSN. Rs-fMRI analysis may provide additional valuable insights into neuronal dysfunctions beyond HD- related structural degeneration and disruptions of functional circuits in HD. Hum Brain Mapp 35:2582

Published
2013

21. Neural correlates of impaired emotion processing in manifest Huntington’s disease

Author

Johannes Schiefer, Cornelius J. Werner, Ferdinand Binkofski, Jörg B. Schulz, Shahram Mirzazade, N. Jon Shah, Imis Dogan, Alexandra Kleiman, Kathrin Reetz, Christian Saß, and Anna Pohl

Subjects
Adult, Male, Cognitive Neuroscience, media_common.quotation_subject, Emotions, Video Recording, Hippocampus, Experimental and Cognitive Psychology, Neuropsychological Tests, Amygdala, Huntington's disease, Neural Pathways, Task Performance and Analysis, medicine, Humans, Prefrontal cortex, media_common, Brain Mapping, medicine.diagnostic_test, Brain, Original Articles, Organ Size, General Medicine, Voxel-based morphometry, medicine.disease, Magnetic Resonance Imaging, Facial Expression, Oxygen, Sadness, Huntington Disease, medicine.anatomical_structure, Pattern Recognition, Visual, nervous system, Female, Atrophy, Functional magnetic resonance imaging, Psychology, Neuroscience, Insula
Abstract

The complex phenotype of Huntington's disease (HD) encompasses motor, psychiatric and cognitive dysfunctions, including early impairments in emotion recognition. In this first functional magnetic resonance imaging study, we investigated emotion-processing deficits in 14 manifest HD patients and matched controls. An emotion recognition task comprised short video clips displaying one of six basic facial expressions (sadness, happiness, disgust, fear, anger and neutral). Structural changes between patients and controls were assessed by means of voxel-based morphometry. Along with deficient recognition of negative emotions, patients exhibited predominantly lower neural response to stimuli of negative valences in the amygdala, hippocampus, striatum, insula, cingulate and prefrontal cortices, as well as in sensorimotor, temporal and visual areas. Most of the observed reduced activity patterns could not be explained merely by regional volume loss. Reduced activity in the thalamus during fear correlated with lower thalamic volumes. During the processing of sadness, patients exhibited enhanced amygdala and hippocampal activity along with reduced recruitment of the medial prefrontal cortex. Higher amygdala activity was related to more pronounced amygdala atrophy and disease burden. Overall, the observed emotion-related dysfunctions in the context of structural neurodegeneration suggest both disruptions of striatal-thalamo-cortical loops and potential compensation mechanism with greater disease severity in manifest HD.

Published
2013

22. Language therapy of aphasia supported by augmented reality applications

Author

Cornelius J. Werner, Roksaneh Kroob, Daniela Antkowiak, Christian Kohlschein, Sabina Jeschke, Maximilian Speicher, and Tobias Meisen

Subjects
Language therapy, Multimedia, business.industry, Everyday activities, 020207 software engineering, 02 engineering and technology, medicine.disease, computer.software_genre, User interface design, 03 medical and health sciences, 0302 clinical medicine, Aphasia, Health care, 0202 electrical engineering, electronic engineering, information engineering, medicine, Natural (music), Language disorder, Augmented reality, medicine.symptom, business, computer, 030217 neurology & neurosurgery, Cognitive psychology
Abstract

In Europe there are more than 580 000 people who suffer from aphasia – an acquired speech and language disorder that occurs because of brain damage, primarily as a result of a stroke. Especially with regards to demographic change, health care systems have to face present and future challenges to improve aphasia therapy. Thereby, immediate therapeutic measures are decisive for best possible and long-term success in language therapy. Regarding essential requirements, on the one hand, therapy intensity and frequency have to be increased significantly while on the other hand, measures need to be adjusted along everyday activities. A very promising approach to meet this requirements are augmented reality applications. They can be used to create a highly natural exercise situation, in which patients interact and practice with their personal possessions at home. This facilitates the successful and continuous transfer of learnings for the patient, contrary to being solely dependent on clinical therapy units. This paper gives an overview of the concept of a real-time software providing augmented and dynamic language therapy, which is interactive and utilizes simple user interface design, for home-based training.

Published
2016

23. Intensive speech and language therapy in patients with chronic aphasia after stroke: a randomised, open-label, blinded-endpoint, controlled trial in a health-care setting

Author

F Reinhuber, B Wilde, U Steller, J Knauss, C Sous-Kulke, E. Bernd Ringelstein, Franziska Wigbers, Wolfram Ziegler, F-J Ferneding, B Gröne, Jörg B. Schulz, K Schulz, W Hofmann, K Krakow, Indra Hempen, Ralf Glindemann, W Schupp, Klaus-Jürgen Schlenck, C Berghoff, Walter Huber, Stefanie Abel, E Schillikowski, F Hamzei, Agnes Flöel, Klaus Willmes, Jonathan List, E König, H Hoffmann, Roman Rocker, K Halm, Frank Regenbrecht, Frank Domahs, S-B Schipke, K Billo, G. Pfeiffer, Christina Rühmkorf, A Oertel, M Bley, O'n Som, A Kartmann, Ana-Claire Meyer, Ernst de Langen, S Runge, Georg Goldenberg, Annette Baumgaertner, F Müller, R Sudhoff, S Krüger, Tanja Grewe, S Bamborschke, D Bätz, I Maser, S Miethe, Peter Martus, Luise Springer, Caterina Breitenstein, Hellmuth Obrig, Stefan Knecht, R Baake, T Keck, Karl Georg Haeusler, Arno Villringer, V Middeldorf, G Klingenberg, M Jöbges, Marion Thomas, and Cornelius J. Werner

Subjects
Adult, Pediatrics, medicine.medical_specialty, Adolescent, Population, Speech Therapy, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Intervention (counseling), Aphasia, Health care, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Adverse effect, education, Stroke, Aged, education.field_of_study, business.industry, Stroke Rehabilitation, General Medicine, Middle Aged, medicine.disease, Chronic Disease, Physical therapy, Language Therapy, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Summary Background Treatment guidelines for aphasia recommend intensive speech and language therapy for chronic (≥6 months) aphasia after stroke, but large-scale, class 1 randomised controlled trials on treatment effectiveness are scarce. We aimed to examine whether 3 weeks of intensive speech and language therapy under routine clinical conditions improved verbal communication in daily-life situations in people with chronic aphasia after stroke. Methods In this multicentre, parallel group, superiority, open-label, blinded-endpoint, randomised controlled trial, patients aged 70 years or younger with aphasia after stroke lasting for 6 months or more were recruited from 19 inpatient or outpatient rehabilitation centres in Germany. An external biostatistician used a computer-generated permuted block randomisation method, stratified by treatment centre, to randomly assign participants to either 3 weeks or more of intensive speech and language therapy (≥10 h per week) or 3 weeks deferral of intensive speech and language therapy. The primary endpoint was between-group difference in the change in verbal communication effectiveness in everyday life scenarios (Amsterdam–Nijmegen Everyday Language Test A-scale) from baseline to immediately after 3 weeks of treatment or treatment deferral. All analyses were done using the modified intention-to-treat population (those who received 1 day or more of intensive treatment or treatment deferral). This study is registered with ClinicalTrials.gov, number NCT01540383. Findings We randomly assigned 158 patients between April 1, 2012, and May 31, 2014. The modified intention-to-treat population comprised 156 patients (78 per group). Verbal communication was significantly improved from baseline to after intensive speech and language treatment (mean difference 2·61 points [SD 4·94]; 95% CI 1·49 to 3·72), but not from baseline to after treatment deferral (−0·03 points [4·04]; −0·94 to 0·88; between-group difference Cohen's d 0·58; p=0·0004). Eight patients had adverse events during therapy or treatment deferral (one car accident [in the control group], two common cold [one patient per group], three gastrointestinal or cardiac symptoms [all intervention group], two recurrent stroke [one in intervention group before initiation of treatment, and one before group assignment had occurred]); all were unrelated to study participation. Interpretation 3 weeks of intensive speech and language therapy significantly enhanced verbal communication in people aged 70 years or younger with chronic aphasia after stroke, providing an effective evidence-based treatment approach in this population. Future studies should examine the minimum treatment intensity required for meaningful treatment effects, and determine whether treatment effects cumulate over repeated intervention periods. Funding German Federal Ministry of Education and Research and the German Society for Aphasia Research and Treatment.

Published
2016

24. Clinical manifestations of intermediate allele carriers in Huntington disease

Author

Cubo E., Ramos-Arroyo M. A., Martinez-Horta S., Martinez-Descalls A., Calvo S., Gil-Polo CAnne-Catherine Bachoud-Lévi, Anna Rita Bentivoglio, Ida Biunno, Raphael M Bonelli, Jean-Marc Burgunder, Stephen B Dunnett, Joaquim J Ferreira, Olivia J Handley, Arvid Heiberg, Torsten Illmann, G Bernhard Landwehrmeyer, Jamie Levey, Maria Ramos-Arroyo, Jørgen E Nielsen, Susana Pro Koivisto, Markku Päivärinta, Raymund A C Roos, Ana Rojo Sebastián, Sarah J Tabrizi, Wim Vandenberghe, Christine Verellen-Dumoulin, Tereza Uhrova, Jan Wahlström, Jacek Zaremba, Verena Baake, Katrin Barth, Adrien Come, Leonor Correia Guedes, Ana Maria Finisterra, Monica Bascuñana Garde, Reineke Bos, Sabrina Betz, Jenny Callaghan, Selene Capodarca, Sébastien Charpentier, Wildson Vieira da Silva, Martina Di Renzo, Daniel Ecker, Ruth Fullam, Camille Genoves, Mette Gilling, Carina Hvalstedt, Christine Held, Andrea Horta-Barba, Kerstin Koppers, Claudia Lamanna, Matilde Laurà, Asunción Martínez Descals, Saul Martinez-Horta, Tiago Mestre, Sara Minster, Daniela Monza, Lisanne Mütze, Martin Oehmen, Helene Padieu, Laurent Paterski, Nadia Peppa, Beate Rindal, Dawn Rogers, Niini Røren, Pavla Šašinková, Yuri Seliverstov, Catherine Taylor, Erika Timewell, Jenny Townhill, Patricia Trigo Cubillo, Marleen R van Walsem, Marie-Noelle Witjes-Ané, Grzegorz Witkowski, Abigail Wright, Elizaveta Yudina, Daniel Zielonka, Eugeniusz Zielonka, Paola Zinzi, Cécile Minet, Pascale Ribaï, Dominique Van Paemel, Lena Hjermind, Oda Jacobsen, Suzanne Lindquist, Jørgen Nielsen, Lisbeth Regeur, Jette Stockholm, Ida Unmack Larsen, Christina Vangsted-Hansen, Tua Vinther-Jensen, Pia Eklund, Heli Hiivola, Hannele Hypponen, Kirsti Martikainen, Katri Tuuha, Philippe Allain, Dominique Bonneau Marie Bost, Bénédicte Gohier, Marie-Anne Guérid, Audrey Olivier, Julie Prouzet, Adriana Prundean, Clarisse Scherer-Gagou, Christophe Verny, Blandine Babiloni, Sabrina Debruxelles, Charlotte Duché, Cyril Goizet, Laetitia Jameau, Danielle Lafoucrière, Umberto Spampinato, Anne-Catherine Bachoud-Lévi, Farideh Badei, Lotfi Boudali, Catherine Bourdet, Laurent Cléret, Maryline Couette, Cécile Focseneanu, Laurie Lemoine, Graça Morgado, Mehdi Sebaiti, Claire Thiriez, Laetitia Vervoitte, Katia Youssov, Jean-Philippe Azulay, Christelle Chabot, Marie Delfini, Alexandre Eusebio, Frédérique Fluchere, Christine Garreau, Aicha Ghenam, Hélène Grosjean, Laura Mundler, Marielle Nowak, Roland Raseta, Maïté Bertrand, Fabienne Calvas, Samia Cheriet, Laurent Marquine, Michèle Pierre, Jérémie Pariente, Sandrine Rolland, Alice Seris, Valérie Vaquie, Christoph Michael Kosinski, Eva Milkereit, Daniela Probst, Kathrin Reetz, Christian Sass, Johannes Schiefer, Christiane Schlangen, Cornelius J Werner, Gisa Ellrichmann, Lennard Herrmann, Rainer Hoffmann, Barbara Kaminski, Carsten Saft, Kai Boelmans, Christos Ganos, Ines Goerendt, Walburgis Heinicke, Ute Hidding, Jan Lewerenz, Alexander Münchau, Michael Orth, Jenny Schmalfeld, Lars Stubbe, Simone Zittel, Gabriele Diercks, Dirk Dressler, Flverly Francis, Sabine Gayde-Stephan, Heike Gorzolla, Bianca Kramer, Rebecca Minschke, Christoph Schrader, Pawel Tacik, Natalie Bechtel, Heike Beckmann, Stefan Bohlen, Nicole Göpfert, Eva Hölzner, Herwig Lange, Ralf Reilmann, Stefanie Rohm, Silke Rumpf, Sigrun Schepers, Nathalia Weber, Michael Bachmeier, Matthias Dose, Nina Hofstetter, Ralf Marquard, Alzbeta Mühlbäck, Andrea Buck, Julia Connemann, Carolin Geitner, Andrea Kesse, Bernhard Landwehrmeyer, Franziska Lezius, Solveig Nepper, Anke Niess, Ariane Schneider, Daniela Schwenk, Sigurd Süssmuth, Sonja Trautmann, Patrick Weydt, Stephan Klebe, Thomas Musacchio, Christine Leypold, Kerstin Nöth, Claudia Cormio, Marina de Tommaso, Anna Rita Dellomonaco, Olimpia Difruscolo, Giovanni Franco, Vittorio Sciruicchio, Claudia Serpino, Michela Figorilli, Francesco Marrosu, Antonella Muroni, Valeria Piras, Melisa Vacca, Caterina Bartoli, Elisabetta Bertini, Fernanda Fortunato, Elena Ghelli, Andrea Ginestroni, Claudia Mechi, Marco Paganini, Silvia Piacentini, Silvia Pradella, Anna Maria Romoli, Sandro Sorbi, Giuseppe De Michele, Luigi Di Maio, Carlo Rinaldi, Marco Massarelli, Silvio Peluso, Alessandro Roca, Cinzia Valeria Russo, Pierpaolo Sorrentino, Elena Salvatore, Tecla Tucci, Milena Cannella, Valentina Codella, Francesca De Gregorio, Annunziata De Nicola, Francesca Elifani, Tiziana Martino, Francesca Lovo, Irene Mazzante, Martina Petrollini, Maria Simonelli, Ferdinando Squitieri, Maurizio Vezza, Barbara D'Alessio, Chiara Esposito, Giulia Coarelli, Michela Ferraldeschi, Marina Frontali, Gioia Jacopini, Giovanni Ristori, Silvia Romano, Monique S E van Hout, Jeroen P P van Vugt, A Marit de Weert, Marloes Verhoeven, Simon J A van den Bogaard, Eve M Dumas, Ellen P 't Hart, Milou Jacobs, Anne Kampstra, Anne Schoonderbeek, Nils Olav Aanonsen, Olaf Aaserud, Liv Barnett, Kathrine Bjørgo, Nancy Borgerød, Elisabeth Dramstad, Madeleine Fannemel, Jan Frich, Helen Gundersen, Per Gørvell, Kathrine Haggag, Cecilie Haggag Johannessen, Lars Retterstøl, Oddveig Rosby, Jutta Rummel, Alma Sikiric, Olga Solberg, Marleen van Walsem, Ragnhild Wehus, Artur Dziadkiewicz, Agnieszka Konkel, Ewa Narożańska, Malgorzata Nowak, Piotr Robowski, Emilia Sitek, Jaroslaw Slawek, Witold Soltan, Michal Szinwelski, Michał Arkuszewski, Magdalena Błaszczyk, Magdalena Boczarska-Jedynak, Ewelina Ciach-Wysocka, Agnieszka Gorzkowska, Barbara Jasińska-Myga, Aleksandra Kaczmarczyk, Gabriela Kłodowska-Duda, Grzegorz Opala, Monika Rudzińska, Daniel Stompel, Krzysztof Banaszkiewicz, Dorota Boćwińska, Kamila Bojakowska-Jaremek, Małgorzata Dec, Natalia Grabska, Malgorzata Krawczyk, Ewelina Kubowicz, Michalina Malec-Litwinowicz, Agata Stenwak, Andrzej Szczudlik, Elżbieta Szczygieł, Magdalena Wójcik, Anna Wasielewska, Jacek Anioła Anna Bryl, Anna Ciesielska, Aneta Klimberg, Jerzy Marcinkowski, Husam Samara, Justyna Sempołowicz, Bartłomiej Wiśniewski, Anna Gogol, Piotr Janik, Zygmunt Jamrozik, Anna Kaminska, Hubert Kwiecinski, Jakub Antczak, Katarzyna Jachinska, Wioletta Krysa, Maryla Rakowicz, Przemyslaw Richter, Rafal Rola, Danuta Ryglewicz, Halina Sienkiewicz-Jarosz, Iwona Stępniak, Anna Sułek, Elzbieta Zdzienicka, Karolina Ziora-Jakutowicz, Cristina Januário, Filipa Júlio, Ana Salgueiro, Miguel Coelho, Tiago Mendes, Mário Miguel Rosa, Anabela Valadas, Cristina Semedo, Ana Calado, Joana Morgado, Margarida Dias, Manuel Almeida, Carmen Durán Herrera, Patrocinio Garcia Moreno, Jordi Bas, Núria Busquets, Matilde Calopa, Serge Jaumà Classen, Nadia Rodríguez Dedichá, Miquel Aguilar Barbera, Sonia Arribas Pardo, Dolors Badenes Guia, Noemi Calzado, Laura Casas Hernanz, Juan Pablo Tartari Díaz-Zorita, Judit López Catena, Pilar Quiléz Ferrer, Gemma Tome Carruesco, Misericordia Floriach Robert, Cèlia Mareca Viladrich, Elvira Roca, Jesús Miguel Ruiz Idiago, Antonio Villa Riballo, Antonia Campolongo, Ramon Fernandez de Bobadilla, Jaime Kulisevsky Bojarsky, Javier Pagonabarraga, Jesus Perez Perez, Carolina Villa, Maria Angeles Acera Gil, Koldo Berganzo Corrales, Juan Carlos Gomez Esteban, Amaia González, Beatriz Tijero Merino, Esther Cubo, Natividad Mariscal, Sandra Gutierrez Romero, José Matías Arbelo, Rocío Malo de Molina, Idaira Martín, Juan Manuel Periañez, Beatriz Udaeta, Fernando Alonso-Frech, Belén Frades, Marina Ávila Villanueva, Maria Ascension Zea Sevilla, Fernando Alonso Frech, María Del Mar Fenollar, Rocío García-Ramos García, Clara Villanueva, Mónica Bascuñana, Marta Fatás Ventura, Juan García Caldentey, Guillermo García Ribas, Justo García de Yébenes, José Luis López-Sendón Moreno, Verónica Mañanes Barral, Cici Feliz Feliz, Pedro José García Ruíz, Ana García, Rosa Guerrero López, Antonio Herranz Bárcenas, Asunción Martínez-Descals, Angel Martínez Pueyo, Veronica Puertas Martin, Noelia Rodríguez Martínez, María José Sainz Artiga, Vicenta Sánchez, Javier Del Val Fernandez, Carmen Antúnez Almagro, Salvadora Manzanares, Juan Marín Muñoz, María Martirio Antequera Torres, Fuensanta Noguera Perea, Laura Vivancos Moreau, Sonia González, Luis Menéndez Guisasola, Carlos Salvador, René Ribacoba, Pablo Sánchez Lozano, Marta Para Prieto, Aránzazu Gorospe, Inés Legarda Ramirez, Penelope Navas Arques, Monica Rodriguez Lopera, Barbara Vives Pastor, Itziar Gaston, Maria Antonia Ramos-Arroyo, Maria Dolores Martinez-Jaurrieta, José Manuel García Moreno, Carolina Mendez Lucena, José Chacón Peña, Fátima Damas Hermoso, Eva Pacheco Cortegana, Luis Redondo, Cristina Melgar Fernandez, Maite Paredes Mata, Maria Dolores Romero Lemos, Maria Bosca, Juan Andres Burguera, Francisco Castera Brugada Carmen Peiró Vilaplana, Elena Bellosta Diago, Javier López Del Val, Laura Martinez Martinez, Elena López, Peter Berglund, Radu Constantinescu, Gunnel Fredlund, Ulrika Høsterey-Ugander, Liselotte Neleborn-Lingefjärd, Yanik Stebler, Alain Kaelin, Irene Romero, Michael Schüpbach, Sabine Weber Zaugg, Lorna Downie, Roisin Jack, Kirsty Matheson, Zosia Miedzybrodzka, Daniela Rae, Sheila A Simpson, Fiona Summers, Alexandra Ure, Vivien Vaughn, Shahbana Akhtar, Jenny Crooks, Adrienne Curtis, Jenny de Souza, John Piedad, Hugh Rickards, Jan Wright, Elizabeth Coulthard, Louise Gethin, Beverley Hayward, Kasia Sieradzan, Monica Busse, Cynthia Butcher, Stephen Dunnett, Catherine Clenaghan, Sarah Hunt, Lesley Jones, Una Jones, Hanan Khalil, Michael Owen, Kathleen Price, Anne Rosser, Peter Brockie, Jillian Foster, Nicola Johns, Sue McKenzie, Jean Rothery, Gareth Thomas, Shona Yates, Alyson Andrew, Julie Frost, Rupert Noad, Jeremy Cosgrove, Deena Gallantree, Stephanie Hamer, Emma Hobson, Stuart Jamieson, Alison Kraus, Mandy Longthorpe, Ivana Markova, Hannah Musgrave, Caroline Peacy, Ashok Raman, Liz Rowett, Jean Toscano, Sue Wild, Carole Clayton, Pam Yardumian, Heather Dipple, Dawn Freire- Patino, Caroline Hallam, Julia Middleton, Uruj Anjum, Jan Coebergh, Charlotte Eddy, Nayana Lahiri, Meriel McEntagart, Michael Patton, Maria Peterson, Sarah Rose, Thomasin Andrews, Stefanie Brown, Stefania Bruno, Elvina Chu, Karen Doherty, Charlotte Golding, Salman Haider, Davina Hensman, Monica Lewis, Marianne Novak, Aakta Patel, Joy Read, Nicola Robertson, Elisabeth Rosser, Sarah Tabrizi, Rachel Taylor, Thomas Warner, Edward Wild, Natalie Arran, Judith Bek, David Craufurd, Marianne Hare, Liz Howard, Susan Huson, Liz Johnson, Mary Jones, Ashok Krishnamoorthy, Helen Murphy, Emma Oughton, Lucy Partington-Jones, Andrea Sollom, Julie Snowden, Cheryl Stopford, Jennifer Thompson, Iris Trender-Gerhard, Nichola Verstraelen, Leann Westmoreland, Ginette Cass, Lynn Davidson, Jill Davison, Neil Fullerton, Katrina Holmes, Suresh Komati, Sharon McDonnell, Zeid Mohammed, Karen Morgan, Lois Savage, Baldev Singh, Josh Wood, Andrea H Nemeth, Gill Siuda, Ruth Valentine, Kathryn Dixon, Richard Armstrong, David Harrison, Max Hughes, Sandra Large, John O Donovan, Amy Palmer, Andrew Parkinson, Beverley Soltysiak, Leanne Timings, Josh Williams, Oliver Bandmann, Alyson Bradbury, Helen Fairtlough, Kay Fillingham, Isabella Foustanos, Paul Gill, Mbombe Kazoka, Kirsty O'Donovan, Louise Nevitt, Oliver Quarrell, Cat Taylor, Katherine Tidswell, Lesley Gowers, Kingsley Powell, Pamela Bethwaite, Rachel Edwards, Kathleen Fuller, Michelle Phillips, Univ Angers, Okina, E., Cubo, M. A., Ramos-Arroyo, S., Martinez-Horta, A., Martinez-Descall, S., Calvo, CAnne-Catherine Bachoud-Lévi, Gil-Polo, Rita Bentivoglio, Anna, Biunno, Ida, M Bonelli, Raphael, Burgunder, Jean-Marc, B Dunnett, Stephen, J Ferreira, Joaquim, J Handley, Olivia, Heiberg, Arvid, Illmann, Torsten, Bernhard Landwehrmeyer, G, Levey, Jamie, Ramos-Arroyo, Maria, E Nielsen, Jørgen, Pro Koivisto, Susana, Päivärinta, Markku, C Roos, Raymund A, Rojo Sebastián, Ana, J Tabrizi, Sarah, Vandenberghe, Wim, Verellen-Dumoulin, Christine, Uhrova, Tereza, Wahlström, Jan, Zaremba, Jacek, Baake, Verena, Barth, Katrin, Come, Adrien, Correia Guedes, Leonor, Maria Finisterra, Ana, Bascuñana Garde, Monica, Bos, Reineke, Betz, Sabrina, Callaghan, Jenny, Capodarca, Selene, Charpentier, Sébastien, Vieira da Silva, Wildson, Di Renzo, Martina, Ecker, Daniel, Fullam, Ruth, Genoves, Camille, Gilling, Mette, Hvalstedt, Carina, Held, Christine, Horta-Barba, Andrea, Koppers, Kerstin, Lamanna, Claudia, Laurà, Matilde, Martínez Descals, Asunción, Martinez-Horta, Saul, Mestre, Tiago, Minster, Sara, Monza, Daniela, Mütze, Lisanne, Oehmen, Martin, Padieu, Helene, Paterski, Laurent, Peppa, Nadia, Rindal, Beate, Rogers, Dawn, Røren, Niini, Šašinková, Pavla, Seliverstov, Yuri, Taylor, Catherine, Timewell, Erika, Townhill, Jenny, Trigo Cubillo, Patricia, R van Walsem, Marleen, Witjes-Ané, Marie-Noelle, Witkowski, Grzegorz, Wright, Abigail, Yudina, Elizaveta, Zielonka, Daniel, Zielonka, Eugeniusz, Zinzi, Paola, Minet, Cécile, Ribaï, Pascale, Van Paemel, Dominique, Hjermind, Lena, Jacobsen, Oda, Lindquist, Suzanne, Nielsen, Jørgen, Regeur, Lisbeth, Stockholm, Jette, Unmack Larsen, Ida, Vangsted-Hansen, Christina, Vinther-Jensen, Tua, Eklund, Pia, Hiivola, Heli, Hypponen, Hannele, Martikainen, Kirsti, Tuuha, Katri, Allain, Philippe, Bonneau Marie Bost, Dominique, Gohier, Bénédicte, Guérid, Marie-Anne, Olivier, Audrey, Prouzet, Julie, Prundean, Adriana, Scherer-Gagou, Clarisse, Verny, Christophe, Babiloni, Blandine, Debruxelles, Sabrina, Duché, Charlotte, Goizet, Cyril, Jameau, Laetitia, Lafoucrière, Danielle, Spampinato, Umberto, Bachoud-Lévi, Anne-Catherine, Badei, Farideh, Boudali, Lotfi, Bourdet, Catherine, Cléret, Laurent, Couette, Maryline, Focseneanu, Cécile, Lemoine, Laurie, Morgado, Graça, Sebaiti, Mehdi, Thiriez, Claire, Vervoitte, Laetitia, Youssov, Katia, Azulay, Jean-Philippe, Chabot, Christelle, Delfini, Marie, Eusebio, Alexandre, Fluchere, Frédérique, Garreau, Christine, Ghenam, Aicha, Grosjean, Hélène, Mundler, Laura, Nowak, Marielle, Raseta, Roland, Bertrand, Maïté, Calvas, Fabienne, Cheriet, Samia, Marquine, Laurent, Pierre, Michèle, Pariente, Jérémie, Rolland, Sandrine, Seris, Alice, Vaquie, Valérie, Michael Kosinski, Christoph, Milkereit, Eva, Probst, Daniela, Reetz, Kathrin, Sass, Christian, Schiefer, Johanne, Schlangen, Christiane, J Werner, Corneliu, Ellrichmann, Gisa, Herrmann, Lennard, Hoffmann, Rainer, Kaminski, Barbara, Saft, Carsten, Boelmans, Kai, Ganos, Christo, Goerendt, Ine, Heinicke, Walburgi, Hidding, Ute, Lewerenz, Jan, Münchau, Alexander, Orth, Michael, Schmalfeld, Jenny, Stubbe, Lar, Zittel, Simone, Diercks, Gabriele, Dressler, Dirk, Francis, Flverly, Gayde-Stephan, Sabine, Gorzolla, Heike, Kramer, Bianca, Minschke, Rebecca, Schrader, Christoph, Tacik, Pawel, Bechtel, Natalie, Beckmann, Heike, Bohlen, Stefan, Göpfert, Nicole, Hölzner, Eva, Lange, Herwig, Reilmann, Ralf, Rohm, Stefanie, Rumpf, Silke, Schepers, Sigrun, Weber, Nathalia, Bachmeier, Michael, Dose, Matthia, Hofstetter, Nina, Marquard, Ralf, Mühlbäck, Alzbeta, Buck, Andrea, Connemann, Julia, Geitner, Carolin, Kesse, Andrea, Landwehrmeyer, Bernhard, Lezius, Franziska, Nepper, Solveig, Niess, Anke, Schneider, Ariane, Schwenk, Daniela, Süssmuth, Sigurd, Trautmann, Sonja, Weydt, Patrick, Klebe, Stephan, Musacchio, Thoma, Leypold, Christine, Nöth, Kerstin, Cormio, Claudia, de Tommaso, Marina, Rita Dellomonaco, Anna, Difruscolo, Olimpia, Franco, Giovanni, Sciruicchio, Vittorio, Serpino, Claudia, Figorilli, Michela, Marrosu, Francesco, Muroni, Antonella, Piras, Valeria, Vacca, Melisa, Bartoli, Caterina, Bertini, Elisabetta, Fortunato, Fernanda, Ghelli, Elena, Ginestroni, Andrea, Mechi, Claudia, Paganini, Marco, Piacentini, Silvia, Pradella, Silvia, Maria Romoli, Anna, Sorbi, Sandro, DE MICHELE, Giuseppe, Di Maio, Luigi, Rinaldi, Carlo, Massarelli, Marco, Peluso, Silvio, Roca, Alessandro, Russo, CINZIA VALERIA, Sorrentino, Pierpaolo, Salvatore, Elena, Tucci, Tecla, Cannella, Milena, Codella, Valentina, De Gregorio, Francesca, De Nicola, Annunziata, Elifani, Francesca, Martino, Tiziana, Lovo, Francesca, Mazzante, Irene, Petrollini, Martina, Simonelli, Maria, Squitieri, Ferdinando, Vezza, Maurizio, D'Alessio, Barbara, Esposito, Chiara, Coarelli, Giulia, Ferraldeschi, Michela, Frontali, Marina, Jacopini, Gioia, Ristori, Giovanni, Romano, Silvia, E van Hout, Monique S, P van Vugt, Jeroen P, Marit de Weert, A, Verhoeven, Marloe, A van den Bogaard, Simon J, M Dumas, Eve, P 't Hart, Ellen, Jacobs, Milou, Kampstra, Anne, Schoonderbeek, Anne, Olav Aanonsen, Nil, Aaserud, Olaf, Barnett, Liv, Bjørgo, Kathrine, Borgerød, Nancy, Dramstad, Elisabeth, Fannemel, Madeleine, Frich, Jan, Gundersen, Helen, Gørvell, Per, Haggag, Kathrine, Haggag Johannessen, Cecilie, Retterstøl, Lar, Rosby, Oddveig, Rummel, Jutta, Sikiric, Alma, Solberg, Olga, van Walsem, Marleen, Wehus, Ragnhild, Dziadkiewicz, Artur, Konkel, Agnieszka, Narożańska, Ewa, Nowak, Malgorzata, Robowski, Piotr, Sitek, Emilia, Slawek, Jaroslaw, Soltan, Witold, Szinwelski, Michal, Arkuszewski, Michał, Błaszczyk, Magdalena, Boczarska-Jedynak, Magdalena, Ciach-Wysocka, Ewelina, Gorzkowska, Agnieszka, Jasińska-Myga, Barbara, Kaczmarczyk, Aleksandra, Kłodowska-Duda, Gabriela, Opala, Grzegorz, Rudzińska, Monika, Stompel, Daniel, Banaszkiewicz, Krzysztof, Boćwińska, Dorota, Bojakowska-Jaremek, Kamila, Dec, Małgorzata, Grabska, Natalia, Krawczyk, Malgorzata, Kubowicz, Ewelina, Malec-Litwinowicz, Michalina, Stenwak, Agata, Szczudlik, Andrzej, Szczygieł, Elżbieta, Wójcik, Magdalena, Wasielewska, Anna, Anioła Anna Bryl, Jacek, Ciesielska, Anna, Klimberg, Aneta, Marcinkowski, Jerzy, Samara, Husam, Sempołowicz, Justyna, Wiśniewski, Bartłomiej, Gogol, Anna, Janik, Piotr, Jamrozik, Zygmunt, Kaminska, Anna, Kwiecinski, Hubert, Antczak, Jakub, Jachinska, Katarzyna, Krysa, Wioletta, Rakowicz, Maryla, Richter, Przemyslaw, Rola, Rafal, Ryglewicz, Danuta, Sienkiewicz-Jarosz, Halina, Stępniak, Iwona, Sułek, Anna, Zdzienicka, Elzbieta, Ziora-Jakutowicz, Karolina, Januário, Cristina, Júlio, Filipa, Salgueiro, Ana, Coelho, Miguel, Mendes, Tiago, Miguel Rosa, Mário, Valadas, Anabela, Semedo, Cristina, Calado, Ana, Morgado, Joana, Dias, Margarida, Almeida, Manuel, Durán Herrera, Carmen, Garcia Moreno, Patrocinio, Bas, Jordi, Busquets, Núria, Calopa, Matilde, Jaumà Classen, Serge, Rodríguez Dedichá, Nadia, Aguilar Barbera, Miquel, Arribas Pardo, Sonia, Badenes Guia, Dolor, Calzado, Noemi, Casas Hernanz, Laura, Pablo Tartari Díaz-Zorita, Juan, López Catena, Judit, Quiléz Ferrer, Pilar, Tome Carruesco, Gemma, Floriach Robert, Misericordia, Mareca Viladrich, Cèlia, Roca, Elvira, Miguel Ruiz Idiago, Jesú, Villa Riballo, Antonio, Campolongo, Antonia, Fernandez de Bobadilla, Ramon, Kulisevsky Bojarsky, Jaime, Pagonabarraga, Javier, Perez Perez, Jesu, Villa, Carolina, Angeles Acera Gil, Maria, Berganzo Corrales, Koldo, Carlos Gomez Esteban, Juan, González, Amaia, Tijero Merino, Beatriz, Cubo, Esther, Mariscal, Natividad, Gutierrez Romero, Sandra, Matías Arbelo, José, Malo de Molina, Rocío, Martín, Idaira, Manuel Periañez, Juan, Udaeta, Beatriz, Alonso-Frech, Fernando, Frades, Belén, Ávila Villanueva, Marina, Ascension Zea Sevilla, Maria, Alonso Frech, Fernando, Del Mar Fenollar, María, García-Ramos García, Rocío, Villanueva, Clara, Bascuñana, Mónica, Fatás Ventura, Marta, García Caldentey, Juan, García Ribas, Guillermo, García de Yébenes, Justo, Luis López-Sendón Moreno, José, Mañanes Barral, Verónica, Feliz Feliz, Cici, José García Ruíz, Pedro, García, Ana, Guerrero López, Rosa, Herranz Bárcenas, Antonio, Martínez-Descals, Asunción, Martínez Pueyo, Angel, Puertas Martin, Veronica, Rodríguez Martínez, Noelia, José Sainz Artiga, María, Sánchez, Vicenta, Del Val Fernandez, Javier, Antúnez Almagro, Carmen, Manzanares, Salvadora, Marín Muñoz, Juan, Martirio Antequera Torres, María, Noguera Perea, Fuensanta, Vivancos Moreau, Laura, González, Sonia, Menéndez Guisasola, Lui, Salvador, Carlo, Ribacoba, René, Sánchez Lozano, Pablo, Para Prieto, Marta, Gorospe, Aránzazu, Legarda Ramirez, Iné, Navas Arques, Penelope, Rodriguez Lopera, Monica, Vives Pastor, Barbara, Gaston, Itziar, Antonia Ramos-Arroyo, Maria, Dolores Martinez-Jaurrieta, Maria, Manuel García Moreno, José, Mendez Lucena, Carolina, Chacón Peña, José, Damas Hermoso, Fátima, Pacheco Cortegana, Eva, Redondo, Lui, Melgar Fernandez, Cristina, Paredes Mata, Maite, Dolores Romero Lemos, Maria, Bosca, Maria, Andres Burguera, Juan, Castera Brugada Carmen Peiró Vilaplana, Francisco, Bellosta Diago, Elena, López Del Val, Javier, Martinez Martinez, Laura, López, Elena, Berglund, Peter, Constantinescu, Radu, Fredlund, Gunnel, Høsterey-Ugander, Ulrika, Neleborn-Lingefjärd, Liselotte, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schüpbach, Michael, Weber Zaugg, Sabine, Downie, Lorna, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, A Simpson, Sheila, Summers, Fiona, Ure, Alexandra, Vaughn, Vivien, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza, Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Busse, Monica, Butcher, Cynthia, Dunnett, Stephen, Clenaghan, Catherine, Hunt, Sarah, Jones, Lesley, Jones, Una, Khalil, Hanan, Owen, Michael, Price, Kathleen, Rosser, Anne, Brockie, Peter, Foster, Jillian, Johns, Nicola, Mckenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Andrew, Alyson, Frost, Julie, Noad, Rupert, Cosgrove, Jeremy, Gallantree, Deena, Hamer, Stephanie, Hobson, Emma, Jamieson, Stuart, Kraus, Alison, Longthorpe, Mandy, Markova, Ivana, Musgrave, Hannah, Peacy, Caroline, Raman, Ashok, Rowett, Liz, Toscano, Jean, Wild, Sue, Clayton, Carole, Yardumian, Pam, Dipple, Heather, Freire- Patino, Dawn, Hallam, Caroline, Middleton, Julia, Anjum, Uruj, Coebergh, Jan, Eddy, Charlotte, Lahiri, Nayana, Mcentagart, Meriel, Patton, Michael, Peterson, Maria, Rose, Sarah, Andrews, Thomasin, Brown, Stefanie, Bruno, Stefania, Chu, Elvina, Doherty, Karen, Golding, Charlotte, Haider, Salman, Hensman, Davina, Lewis, Monica, Novak, Marianne, Patel, Aakta, Read, Joy, Robertson, Nicola, Rosser, Elisabeth, Tabrizi, Sarah, Taylor, Rachel, Warner, Thoma, Wild, Edward, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Krishnamoorthy, Ashok, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iri, Verstraelen, Nichola, Westmoreland, Leann, Cass, Ginette, Davidson, Lynn, Davison, Jill, Fullerton, Neil, Holmes, Katrina, Komati, Suresh, Mcdonnell, Sharon, Mohammed, Zeid, Morgan, Karen, Savage, Loi, Singh, Baldev, Wood, Josh, H Nemeth, Andrea, Siuda, Gill, Valentine, Ruth, Dixon, Kathryn, Armstrong, Richard, Harrison, David, Hughes, Max, Large, Sandra, O Donovan, John, Palmer, Amy, Parkinson, Andrew, Soltysiak, Beverley, Timings, Leanne, Williams, Josh, Bandmann, Oliver, Bradbury, Alyson, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Gill, Paul, Kazoka, Mbombe, O'Donovan, Kirsty, Nevitt, Louise, Quarrell, Oliver, Taylor, Cat, Tidswell, Katherine, Gowers, Lesley, Powell, Kingsley, Bethwaite, Pamela, Edwards, Rachel, Fuller, Kathleen, Phillips, Michelle, Cubo, E., Ramos-Arroyo, M. A., Martinez-Horta, S., Martinez-Descalls, A., Russo, C. V., Calvo, S., Gil-Polo, C., Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), Ramos-Arroyo, María A., Martínez-Descalls, Asunción, Calvo, Sara, and Gil-Polo, Cecilia

Subjects
0301 basic medicine, Registrie, Adult, Male, medicine.medical_specialty, Aging, Heterozygote, Genetic counseling, Motor Disorders, Disease, Severity of Illness Index, 03 medical and health sciences, Cognition Disorder, 0302 clinical medicine, Trinucleotide Repeats, Internal medicine, medicine, Humans, Registries, Allele, Motor Disorder, Alleles, Huntingtin Protein, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Medicine (all), Trinucleotide Repeat, Cognition, Genetic Status, Middle Aged, Phenotype, Europe, Settore MED/26 - NEUROLOGIA, 030104 developmental biology, Huntington Disease, Case-Control Studies, Cohort, medicine (all), neurology (clinical), controlled clinical trial (topic), Quality of Life, Female, Neurology (clinical), business, Case-Control Studie, Cognition Disorders, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Human
Abstract

International audience; OBJECTIVE: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry.METHODS: We assessed a cohort of participants at risk with RESULTS: Of 12,190 participants, 657 (5.38%) with CONCLUSIONS: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling.CLINICALTRIALSGOV IDENTIFIER: NCT01590589.

Published
2016

25. Cognition in Friedreich's ataxia : a behavioral and multimodal imaging study

Author

Kathrin Reetz, Cornelius J. Werner, Eugenie Tinnemann, Stefanie Schulz, Dagmar Timmann, Shahram Mirzazade, Thomas Klockgether, Jörg B. Schulz, Kathrin Fedosov, Ilaria Giordano, Imis Dogan, Stefan Heim, Sandro Romanzetti, and Ana Sofia Costa

Subjects
Cerebellum, Ataxia, Medizin, behavioral disciplines and activities, 050105 experimental psychology, White matter, 03 medical and health sciences, 0302 clinical medicine, Medicine, Verbal fluency test, 0501 psychology and cognitive sciences, ddc:610, business.industry, Working memory, General Neuroscience, 05 social sciences, Neuropsychology, 3. Good health, medicine.anatomical_structure, nervous system, Neurology (clinical), medicine.symptom, business, Neurocognitive, Neuroscience, 030217 neurology & neurosurgery, Motor cortex, Research Paper
Abstract

Objective Friedreich's ataxia (FRDA) is a spinocerebellar degenerative disorder, in which cognitive deficits are sparsely explored. In this behavioral and multimodal magnetic resonance imaging (MRI) study, we investigated the neurocognitive profile and cortico-cerebellar dysfunctions underlying executive functioning in individuals with FRDA. Methods 22 FRDA patients and 22 controls were clinically and neuropsychologically examined. Fifteen of each underwent structural and functional MRI using a verbal-fluency task with phonemic and semantic conditions. Gray (GM) and white matter (WM) alterations were assessed by means of voxel-based morphometry and diffusion-tensor imaging. Results The neuropsychological profile demonstrated deficits in verbal fluency, working memory and social cognition. Functional MRI data showed most pronounced group-differences in phonemic fluency with patients exhibiting enhanced activity in the cerebellum (VI, Crus I), fronto-insular, premotor and temporo-occipital regions. The semantic condition only revealed reduced activity in the anterior cerebellum; for overt speech, we found increased activity in the motor cortex. Functional connectivity-analysis showed higher co-activation within cerebellar and cortical regions, respectively, and impaired interregional coupling between the cerebellum and fronto-insular cortex for phonemic processing, which was also related to poorer task performance. GM reduction in FRDA was mainly found in lobule VI, whereas WM degeneration was more pronounced including brainstem, cerebellum, and cortex. Decreased cerebellar GM was associated with enhanced activity in the fronto-insular cortex, while loss of WM integrity may translate cortico-cerebellar pathway disruptions. Interpretation The pattern of increased neural response with both cerebellar and cortical involvement underlying executive functioning indicates functional reorganization driven by disease-related structural damage in FRDA.

Published
2016

26. Posterior Cortical Atrophy: A Case Report of a 6-Year Natural Progression

Author

Cornelius J. Werner, Ana Sofia Costa, Arno Reich, Ines Ann Heber, Jörg B. Schulz, Ulrike Schöne, and Kathrin Reetz

Subjects
050103 clinical psychology, Pathology, medicine.medical_specialty, Time Factors, Disease, Neuropsychological Tests, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Alzheimer Disease, medicine, Corticobasal degeneration, Dementia, Humans, 0501 psychology and cognitive sciences, Cerebral Cortex, Lewy body, business.industry, 05 social sciences, Neuropsychology, Posterior cortical atrophy, Neurodegenerative Diseases, Middle Aged, medicine.disease, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Disease Progression, Female, Geriatrics and Gerontology, Alzheimer's disease, Atrophy, business, Gerontology, 030217 neurology & neurosurgery
Abstract

BACKGROUND We describe a 6-year natural history of a patient with posterior cortical atrophy (PCA), demonstrating the difficulties of diagnosis in the early stages of the disease. First clinical signs were predominantly visual with normal neuroimaging and neurodegeneration markers. The mild clinical signs were followed by a progressive decline of various cognitive functions, including perception, attention, memory, and executive function. Repeated neuroimaging and cerebrospinal fluid (CSF) measurements finally revealed a PCA with underlying atypical Alzheimer disease (AD) pathology. PCA is a neurodegenerative syndrome characterized by progressive deterioration of visuospatial, visuoperceptual, praxic, and literacy abilities due to degeneration of posterior cortical regions.1 Pathologic studies show that this often underrecognized syndrome is associated with a range of different disease pathologies. Most commonly it is attributed to AD, but it may also be caused by Lewy body dementia, corticobasal degeneration, and prion diseases, such as Creutzfeld-Jakob disease or familial fatal insomnia.2 PCA often presents a considerable challenge in differential diagnostics because of its initial disease characteristics being quite distinct from other dementias. Here we present a case of PCA which was followed up for almost 6 years with extensive clinical, neuropsychological, neuroimaging, and CSF biomarker testing.

Published
2015

27. Altered motor network activation and functional connectivity in adult tourette's syndrome

Author

Thilo Kellermann, Margarete Beldoch, Jon Shah, Cornelius J. Werner, Jessica Bath, Hans Peter Wegener, Tony Stöcker, Irene Neuner, and Frank Schneider

Subjects
Adult, Male, Cingulate cortex, Aging, medicine.medical_specialty, Tics, Audiology, Tourette syndrome, Young Adult, Cognition, International Classification of Diseases, Neural Pathways, Motor system, Image Processing, Computer-Assisted, medicine, Humans, Radiology, Nuclear Medicine and imaging, Young adult, Research Articles, Cerebral Cortex, Motor Neurons, Principal Component Analysis, Radiological and Ultrasound Technology, medicine.diagnostic_test, Motor control, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Diagnostic and Statistical Manual of Mental Disorders, Neurology, Female, Neurology (clinical), Nerve Net, Anatomy, Psychology, Functional magnetic resonance imaging, Neuroscience, Psychomotor Performance, Tourette Syndrome
Abstract

Tourette's syndrome (TS) is a developmental neuropsychiatric disorder characterized by motor and vocal tics as well as psychiatric comorbidities. Disturbances of the fronto‐striatal‐thalamic pathways responsible for motor control and impulse inhibition have been previously described in other studies. Although differences in motor performance are well recognized, imaging data elucidating the neuronal correlates are scarce. Here, we examined 19 adult TS patients (13 men, aged 22–52 years, mean = 34.3 years) and 18 age‐ and sex‐matched controls (13 men, aged 24–57 years, mean = 37.6 years) in a functional magnetic resonance imaging study at 1.5 T. We corrected for possible confounds introduced by tics, motion, and brain‐structural differences as well as age, sex, comorbidities, and medication. Patients and controls were asked to perform a sequential finger‐tapping task using their right, left, and both hands, respectively. Task performance was monitored by simultaneous MR‐compatible video recording. Although behavioral data obtained during scanning did not show significant differences across groups, we observed differential neuronal activation patterns depending on both handedness (dominant vs. nondominant) and tapping frequency in frontal, parietal, and subcortical areas. When controlling for open motor performance, a failure of deactivation in easier task conditions was found in the subgenual cingulate cortex in the TS patients. In addition, performance‐related functional connectivity of lower‐ and higher‐order motor networks differed between patients and controls. In summary, although open performance was comparable, patients showed different neuronal networks and connectivity patterns when performing increasingly demanding tasks, further illustrating the impact of the disease on the motor system. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.

Published
2011

28. Altered amygdala functional connectivity in adult Tourette’s syndrome

Author

Tony Stöcker, Irene Neuner, Thilo Kellermann, N. Jon Shah, Cornelius J. Werner, Hans Peter Wegener, and Frank Schneider

Subjects
Adult, Male, Tics, Tourette syndrome, Amygdala, Functional Laterality, Young Adult, Neural Pathways, Image Processing, Computer-Assisted, medicine, Cluster Analysis, Humans, Pharmacology (medical), Young adult, Biological Psychiatry, medicine.diagnostic_test, Functional connectivity, Case-control study, Magnetic resonance imaging, General Medicine, medicine.disease, Magnetic Resonance Imaging, Oxygen, Psychiatry and Mental health, medicine.anatomical_structure, Case-Control Studies, Female, Functional magnetic resonance imaging, Psychology, Neuroscience, Psychomotor Performance, Tourette Syndrome
Abstract

Tourette's syndrome (TS) is a developmental neuropsychiatric disorder characterized by motor and vocal tics as well as psychiatric comorbidities. Recently, differences in maturation of cortical networks using functional connectivity metrics have been described for this disorder. However, adult data on subcortical networks are scarce. In particular, the connectivity of the amygdala, for which a role in the pathophysiology of TS has been established, has not been examined so far. We studied 15 adult TS patients (11 male, aged 30.4 ± 9.7y) and 15 age- and sex-matched controls (11 male, aged 32.0 ± 9.3y) in a functional magnetic resonance imaging study at 1.5T using a simple motor task. We corrected for possible confounds introduced by tics, motion and brain-structural differences as well as age, sex, and medication. Task performance was monitored by simultaneous MR-compatible video-recording. Data were analyzed using an independent component approach sensitive to functional connectivity patterns. A stable component comprising both amygdalae could be identified across all subjects. Additionally, we observed a highly significant increase in coupling between/within amygdalae in the TS group when compared to controls, although behavioral data obtained during scanning did not show significant differences. These findings are expected to add to our understanding of the functional architecture of Tourette's syndrome.

Published
2010

29. Tau pathology in Huntington's disease: A brief in vivo PET-imaging report

Author

Thilo van Eimeren, Kathrin Giehl, Jörg B. Schulz, Imis Dogan, Cornelius J. Werner, Alexander Drzezga, Jochen Hammes, and Kathrin Reetz

Subjects
Pathology, medicine.medical_specialty, Tau pathology, 010405 organic chemistry, business.industry, Pet imaging, 010402 general chemistry, medicine.disease, 01 natural sciences, 0104 chemical sciences, Neurology, Huntington's disease, In vivo, medicine, Neurology (clinical), business
Published
2017

30. The Default Mode Network and EEG Regional Spectral Power: A Simultaneous fMRI-EEG Study

Author

Irene Neuner, Jorge Arrubla, Cornelius J Werner, Konrad Hitz, Frank Boers, Wolfram Kawohl, N Jon Shah, and University of Zurich

Subjects
Adult, Male, Anatomy and Physiology, Neural Networks, Cognitive Neuroscience, lcsh:Medicine, 610 Medicine & health, Neuroimaging, 1100 General Agricultural and Biological Sciences, Young Adult, 1300 General Biochemistry, Genetics and Molecular Biology, Diagnostic Medicine, Humans, lcsh:Science, Biology, Clinical Neurophysiology, Brain Mapping, lcsh:R, fMRI, Brain, Electroencephalography, Brain Waves, Magnetic Resonance Imaging, Electrophysiology, Neurology, 10054 Clinic for Psychiatry, Psychotherapy, and Psychosomatics, Medicine, lcsh:Q, Female, ddc:500, Research Article, Neuroscience
Abstract

PLoS one 9(2), e88214 (2014). doi:10.1371/journal.pone.0088214, Published by PLoS [u.a.], Lawrence, Kan.

Published
2014

31. D26 Pathological tau signal in huntington’s disease – an in vivo [18F]-AV-1451 pet imaging report

Author

Alexander Drzezga, Cornelius J. Werner, Thilo van Eimeren, Jörg B. Schulz, Kathrin Giehl, Jochen Hammes, Imis Dogan, Bernd Neumaier, and Kathrin Reetz

Subjects
Cerebellum, biology, business.industry, Neurodegeneration, Tau protein, Striatum, medicine.disease, Psychiatry and Mental health, medicine.anatomical_structure, Huntington's disease, In vivo, Cortex (anatomy), medicine, biology.protein, Surgery, Neurology (clinical), Nuclear medicine, business, Pathological
Abstract

Background Tau aggregation has been implicated in the pathological process and clinical expression in Huntington’s disease (HD). Detection of cerebral pathological Tau protein deposits may therefore be useful to track and predict disease progression. Methods We report on three manifest HD patients, who underwent [18F]AV-1451 PET and were compared to age-matched controls. PET images were acquired using a PET-Siemens Biograph mCT Flow-Edge 128 scanner (Siemens, Knoxville, TN). All patients were scanned for 15 minutes, 97 ± 10 minutes after intravenous injection of 218 ± 95 MBq of [18F]-AV-1451. PET scans were co-registered to the corresponding high-resolution anatomical MR images (3 T Prisma Siemens, Erlangen) and spatially normalised to stereotactic MNI space using the normalisation parameters acquired during MR segmentation. Results We found pathological in vivo Tau signal in HD mainly in the striatum, but also in the cortex and cerebellum. Patient 3, who was cognitively least impaired, displayed the weakest subcortical and cortical signal, while highest tau tracer uptake was observed in patient 2, presenting longest disease duration and highest total motor score as well as disease burden score. Conclusions We conclude that Tau PET imaging in HD may enable the assessment of propagation of tau deposition, its relation to neurodegeneration and effects of potential disease-modifying interventions.

Published
2016

32. D14 Resting-state connectivity changes in huntington’s disease: a follow-up study

Author

Imis Dogan, Kathrin Reetz, Shahram Mirzazade, Jörg B. Schulz, Cornelius J. Werner, and Johannes Schiefer

Subjects
medicine.medical_specialty, medicine.diagnostic_test, Resting state fMRI, Brain activity and meditation, business.industry, Context (language use), Striatum, medicine.disease, computer.software_genre, Psychiatry and Mental health, Atrophy, Huntington's disease, Voxel, Internal medicine, medicine, Cardiology, Surgery, Neurology (clinical), Functional magnetic resonance imaging, business, computer
Abstract

Introduction In a recent functional MRI study we investigated the integrity of resting-state networks (RSN) in Huntington’s disease (HD) and reported significant increases in intrinsic functional connectivity including the thalamus, striatum, prefrontal, premotor and parietal maps.1 The aim of the present study was to follow up these findings and to assess RSN changes in HD longitudinally. Methods Ten HD patients (3 pre-, 7 manifest) and ten controls matched for age and gender underwent 3T MRI at two visits (mean scan interval HD: 22 ± 4 months; controls: 25 ± 6). Resting-state data were analysed using independent component analysis and subsequent dual-regression.2,3 Structural changes were analysed by means of voxel-based morphometry (VBM). Results Patients did not show substantial clinical decline over time. VBM revealed HD-typical striatal and cortical atrophy at both time-points, but no group-by-time interaction. RSN analysis at baseline showed increased intrinsic connectivity in HD compared to controls in striatal and fronto-striatal components. Longitudinally, we found group-by-time interactions showing an attenuation of the increased coherence mainly in fronto-striatal RSN in HD. Functional connectivity drop-off was more pronounced in HD stages II-III, whereas premanifest subjects were more stable over time. Baseline striatal volumes correlated negatively with the difference in functional connectivity over time, indicating that patients with more pronounced atrophy seem to have a higher drop-off from baseline to follow-up. Conclusions The pattern of increased intrinsic connectivity in HD might suggest a reduced ability of intra-network differentiation and potential functional compensatory mechanisms. As disease pathology progresses over time increased neural coupling seems to attenuate, possibly due to progression of cell degeneration. The prognostic value of our findings needs to be evaluated in a larger sample in the context of clinical and structural decline. References Werner CJ, Dogan I, Sass C, Mirzazade S, Schiefer J, Shah NJ, Schulz JB, Reetz K. ‘Altered resting-state connectivity in Huntington’s disease’, Human Brain Mapping 2013 Beckmann CF and Smith SM. ‘Probabilistic Independent Component Analysis for Functional Magnetic Resonance Imaging’, IEEE Transactions on Medical Imaging 2004;23(2):137–152 Filippini N, MacIntosh BJ, Hough MG, Goodwin GM, Frisoni GB, Smith SM, Matthews PM, Beckmann CF, Mackay CE. ‘Distinct patterns of brain activity in young carriers of the APOE-e4 allele’, PNAS 2009;106(17):7,209–7,214

Published
2016

33. Increased brain tissue sodium concentration in Huntington's Disease - a sodium imaging study at 4 T

Author

Sandro Romanzetti, Imis Dogan, Cornelius J. Werner, Jörg B. Schulz, Christian Saß, Johannes Schiefer, N. Jon Shah, and Kathrin Reetz

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Cognitive Neuroscience, Sodium, chemistry.chemical_element, Hippocampus, Striatum, Grey matter, Sensitivity and Specificity, Huntington's disease, mental disorders, medicine, Humans, medicine.diagnostic_test, business.industry, Putamen, Neurodegeneration, Brain, Reproducibility of Results, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Huntington Disease, Neurology, chemistry, Female, business, Biomarkers
Abstract

The neuropathological hallmark of the autosomal dominantly inherited, neurodegenerative disorder Huntington's disease is progressive striatal loss starting several years prior to symptom manifestation. Magnetic resonance (MR) imaging has been widely used to detect altered structure in premanifest and early Huntington's disease. Given that neurodegeneration is likely preceded by substantial neuronal dysfunction, we used in vivo sodium MR imaging, which has been shown to be sensitive to cell death and viability, to investigate cellular and metabolic integrity of Huntington's disease brain tissue. We studied a total of thirteen healthy controls and thirteen Huntington's disease gene carriers (11 manifest and 2 premanifest). The manifest Huntington's disease group was subdivided into stages 1 and 2 according to their Total Functional Capacity scores. Clinical total motor and cognitive scores, as well as calibrated sodium and T1-weighted MR images were obtained with a 4 T Siemens MR scanner. Sodium images were acquired by means of a constant time imaging technique with an ultra-short “echo time”. T1-weighted MR images were further analysed with voxel-based morphometry. The absolute total sodium concentration and grey matter values were measured in several Huntington's disease‐specific and also non-specific areas. Statistical analysis of variance and Pearson correlation were applied. In Huntington's disease subjects, we found an increase of total sodium concentration of the entire brain compared to controls. Increased total sodium concentration values were found in structurally affected, but also in some non-affected, regions. The highest total sodium concentration values were found in the bilateral caudate, which was associated with caudate grey matter atrophy and CAG repeat length. In all Huntington's disease subjects we further found a profound increase of total sodium concentration in the putamen, pallidum, thalamus, hippocampus, insula, precuneus and occipital cortex compared to controls. No change of total sodium concentration was observed in the amygdala, pre- and postcentral gyrus, frontal and temporal cortices or in the cerebellum. This is the first in vivo sodium MR imaging study carried out on a 4 T MR scanner in Huntington's disease gene carriers demonstrating a significant enhancement in sodium concentration in the bilateral striatum, a key region in Huntington's disease, and also in other disease-related atrophic areas. Sodium MR imaging may provide a deeper insight into the pathophysiological mechanisms of tissue degeneration in Huntington's disease, presenting potential to detect changes preceding neurodegeneration.

Published
2012

34. Aorto-left-ventricular tunnel: A rare cause of cardioembolic stroke in a 42-year-old patient

Author

R. Hoffmann, K. Brehmer, Jörg B. Schulz, Cornelius J. Werner, E. Mühler, Arno Reich, and Frank A. Wollenweber

Subjects
Adult, Male, medicine.medical_specialty, Cardioembolic stroke, Ataxia, business.industry, Heart Ventricles, Vascular risk, Asymptomatic, Embolic stroke, Stroke, Diffusion Magnetic Resonance Imaging, Echocardiography, medicine.artery, Internal medicine, Cerebellum, Ascending aorta, cardiovascular system, medicine, Cardiology, Humans, Neurology (clinical), medicine.symptom, business, Aorta
Abstract

A 42-year-old man presented with acute ataxia resulting from an embolic stroke without classic vascular risk factors but revealing a hitherto clinically asymptomatic aorto-ventricular tunnel, which is defined by a hereditary connection between the ascending aorta and one of the ventricles (figure).1 We postulate that blood turbulences around the tortuous tunnel with a stenotic component …

Published
2011

35. Proteome analysis of human substantia nigra in Parkinson's disease

Author

Sabine Wolf, Roland Hans Heyny-von Haussen, Cornelius J. Werner, and Gerhard Mall

Subjects
Parkinson's disease, lcsh:Cytology, Protein subunit, Research, Substantia nigra, Biology, Proteomics, medicine.disease, Biochemistry, Annexin, Proteome, medicine, Rab, lcsh:QH573-671, Protein disulfide-isomerase, Molecular Biology
Abstract

Background Parkinson's disease (PD) is the most common neurodegenerative disorder involving the motor system. Although not being the only region involved in PD, affection of the substantia nigra and its projections is responsible for some of the most debilitating features of the disease. To further advance a comprehensive understanding of nigral pathology, we conducted a tissue based comparative proteome study of healthy and diseased human substantia nigra. Results The gross number of differentially regulated proteins in PD was 221. In total, we identified 37 proteins, of which 16 were differentially expressed. Identified differential proteins comprised elements of iron metabolism (H-ferritin) and glutathione-related redox metabolism (GST M3, GST P1, GST O1), including novel redox proteins (SH3BGRL). Additionally, many glial or related proteins were found to be differentially regulated in PD (GFAP, GMFB, galectin-1, sorcin), as well as proteins belonging to metabolic pathways sparsely described in PD, such as adenosyl homocysteinase (methylation), aldehyde dehydrogenase 1 and cellular retinol-binding protein 1 (aldehyde metabolism). Further differentially regulated proteins included annexin V, beta-tubulin cofactor A, coactosin-like protein and V-type ATPase subunit 1. Proteins that were similarly expressed in healthy or diseased substantia nigra comprised housekeeping proteins such as COX5A, Rho GDI alpha, actin gamma 1, creatin-kinase B, lactate dehydrogenase B, disulfide isomerase ER-60, Rab GDI beta, methyl glyoxalase 1 (AGE metabolism) and glutamine synthetase. Interestingly, also DJ-1 and UCH-L1 were expressed similarly. Furthermore, proteins believed to serve as internal standards were found to be expressed in a constant manner, such as 14-3-3 epsilon and hCRMP-2, thus lending further validity to our results. Conclusion Using an approach encompassing high sensitivity and high resolution, we show that alterations of SN in PD include many more proteins than previously thought. The results point towards a heterogeneous aetiopathogenesis of the disease, including alterations of GSH-related proteins as well as alterations of proteins involved in retinoid metabolism, and they indicate that proteins involved in familial PD may not be differentially regulated in idiopathic Parkinson's disease.

Published
2007

36. Clinical diagnosis and management in early Huntington's disease: a review

Author

Johannes Schiefer, Kathrin Reetz, and Cornelius J. Werner

Subjects
medicine.medical_specialty, Pharmacotherapy, Huntington's disease, business.industry, Clinical diagnosis, Neurodegeneration, medicine, Cognition, Disease, Intensive care medicine, business, medicine.disease, Progressive disease
Abstract

This review focuses on clinical diagnosis and both pharmacological and nonpharmacological therapeutic options in early stages of the autosomal dominant inherited neurodegenerative Huntington's disease (HD). The available literature has been reviewed for motor, cognitive, and psychiatric alterations, which are the three major symptom domains of this devastating progressive disease. From a clinical point of view, one has to be aware that the HD phenotype can vary highly across individuals and during the course of the disease. Also, symptoms in juvenile HD can differ substantially from those with adult-onset of HD. Although there is no cure of HD and management is limited, motor and psychiatric symptoms often respond to pharmacotherapy, and nonpharmacological approaches as well as supportive care are essential. International treatment recommendations based on study results, critical statements, and expert opinions have been included. This review is restricted to symptomatic and supportive approaches since all attempts to establish a cure for the disease or modifying therapies have failed so far.

Published
2015

37. Diminished Activation of Motor Working-Memory Networks in Parkinson's Disease

Author

Imis Dogan, N. Jon Shah, Martin Kronenbuerger, Simon B. Eickhoff, Kathrin Reetz, Robert Langner, Jörg B. Schulz, Claudia Rottschy, Cornelius J. Werner, Shahram Mirzazade, and Alexandra Kleiman

Subjects
Male, Cerebellum, Parkinson's disease, lcsh:Medicine, Neuropsychological Tests, Cognition, 0302 clinical medicine, Neural Pathways, Basal ganglia, Medicine, lcsh:Science, Movement Disorders, Multidisciplinary, medicine.diagnostic_test, Cognitive Neurology, fMRI, 05 social sciences, Parietal lobe, Brain, Neurodegenerative Diseases, Parkinson Disease, Magnetic Resonance Imaging, Memory, Short-Term, medicine.anatomical_structure, Neurology, Female, ddc:500, Research Article, Cognitive Neuroscience, Neuroimaging, Motor Activity, 050105 experimental psychology, 03 medical and health sciences, Motor system, Humans, 0501 psychology and cognitive sciences, Working Memory, Biology, Aged, Demography, Behavior, Recall, Working memory, business.industry, lcsh:R, medicine.disease, Case-Control Studies, Mental Recall, lcsh:Q, business, Functional magnetic resonance imaging, Neuroscience, 030217 neurology & neurosurgery
Abstract

PLoS one 8(4), e61786 (2013). doi:10.1371/journal.pone.0061786, Published by PLoS [u.a.], Lawrence, Kan.

Published
2013

38. Impaired Motor Networks in Tourette's Syndrome

Author

Tony Stoecker, Frank Schneider, HP Wegener, M Beldoch, Cornelius J. Werner, Thilo Kellermann, Irene Neuner, and JN Shah

Subjects
medicine.medical_specialty, Neurology, Cognitive Neuroscience, Tourette's syndrome, medicine, Audiology
Published
2009

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