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198 results on '"Mühlau M"'

4. Retinal ganglion cell loss is associated with future disability worsening in early relapsing remitting multiple sclerosis

Author

Wauschkuhn, J., Solorza Buenrostro, G., Aly, L., Asseyer, S., Wicklein, R., Hartberger, J.M., Ruprecht, K., Mühlau, M., Schmitz-Hübsch, T., Chien, C., Berthele, A., Brandt, A.U., Korn, T., Paul, F., Hemmer, B., Zimmermann, H.G., and Knier, B.

Subjects
Function and Dysfunction of the Nervous System
Abstract

BACKGROUND: Thinning of the retinal combined ganglion cell and inner plexiform layer (GCIP) as measured by optical coherence tomography (OCT) is a common finding in patients with multiple sclerosis. This study aimed to investigate whether a single retinal OCT analysis allows prediction of future disease activity after a first demyelinating event. METHODS: Observational cohort study including 201 patients with recently diagnosed clinically isolated syndrome or relapsing remitting multiple sclerosis from two German tertiary referral centers. Individuals underwent neurological examination, MRI and OCT at baseline and at yearly follow-up visits. RESULTS: Patients were included at a median disease duration of 2.0 months. During a median follow-up of 59 (interquartile range 43 - 71) months, 82% of patients had ongoing disease activity as demonstrated by failing the no evidence of disease activity (NEDA)-3 criteria and 19% presented with confirmed disability worsening. A GCIP threshold ≤ 77 μm at baseline identified patients with a high risk for NEDA-3 failure (hazard ratio 1.7 [95% CI 1.1 - 2.8], p=0.04) and GCIP measures ≤ 69 μm predicted disability worsening (hazard ratio 2.2 (95% CI, 1.2 - 4.3); p=0.01). Higher rates of annualized GCIP loss increased the risk for disability worsening (hazard ratio 2.5 per 1 μm/year increase of GCIP loss, p=0.03). CONCLUSIONS: Ganglion cell thickness as measured by OCT after the initial manifestation of multiple sclerosis may allow early risk stratification as to future disease activity and progression.

Published
2023

5. Early spinal cord pseudoatrophy in interferon-beta treated multiple sclerosis

Author

Matusche, B., Litvin, L., Schneider, R., Bellenberg, B., Mühlau, M., Pongratz, V., Berthele, A., Groppa, S., Muthuraman, M., Zipp, F., Paul, F., Wiendl, H., Meuth, S.G., Sämann, P., Weber, F., Linker, R.A., Kümpfel, T., Gold, R., and Lukas, C.

Subjects
Function and Dysfunction of the Nervous System
Abstract

BACKGROUND: Brain pseudoatrophy has been shown to play a pivotal role in the interpretation of brain atrophy measures during the first year of disease-modifying therapy in multiple sclerosis. Whether pseudoatrophy also affects the spinal cord remains unclear. The aim of this study was to analyze the extent of pseudoatrophy in the upper spinal cord during the first two years after therapy initiation and compare this to the brain. METHODS: A total of 129 patients from a prospective longitudinal multicentric national cohort study for whom MRI scans at baseline, 12 months and 24 months were available were selected for brain and spinal cord volume quantification. Annual percentage brain volume and cord area change were calculated using SIENA and NeuroQLab, respectively. Linear mixed model analyses were performed to compare patients on interferon-beta therapy (n = 84) and untreated patients (n = 45). RESULTS: Patients treated with interferon-beta demonstrated accelerated annual percentage brain volume and cervical cord area change in the first year after treatment initiation, whereas atrophy rates stabilized to a similar and not significantly different level compared to untreated patients during the second year. CONCLUSIONS: These results suggest that pseudoatrophy occurs not only in the brain, but also in the spinal cord during the first year of interferon-beta treatment.

Published
2023

12. Inner retinal layer thinning in radiologically isolated syndrome predicts conversion to multiple sclerosis

Author

Aly, L., primary, Havla, J., additional, Lepennetier, G., additional, Andlauer, T. F. M., additional, Sie, C., additional, Strauß, E.‐M., additional, Hoshi, M.‐M., additional, Kümpfel, T., additional, Hiltensperger, M., additional, Mitsdoerffer, M., additional, Mühlau, M., additional, Zimmer, C., additional, Hemmer, B., additional, Korn, T., additional, and Knier, B., additional

Published
2020
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17. Structural Brain Changes in Tinnitus

Author

Mühlau, M., Rauschecker, J. P., Oestreicher, E., Gaser, C., Röttinger, M., Wohlschläger, A. M., Simon, F., Etgen, T., Conrad, B., and Sander, D.

Published
2006

21. Volume versus surface-based cortical thickness measurements: A comparative study with healthy controls and multiple sclerosis patients

Author

Righart, R., Schmidt, P., Dahnke, R., Biberacher, V., Beer, A., Buck, D., Hemmer, B., Kirschke, J. S., Zimmer, C., Gaser, C., and Mühlau, M.

Subjects
Central Nervous System, Adult, Male, Computer and Information Sciences, Multiple Sclerosis, Imaging Techniques, Immunology, lcsh:Medicine, Research and Analysis Methods, Pathology and Laboratory Medicine, Nervous System, Autoimmune Diseases, Diagnostic Radiology, Signs and Symptoms, Diagnostic Medicine, Medicine and Health Sciences, Image Processing, Computer-Assisted, Humans, Animal Anatomy, Gray Matter, lcsh:Science, Cerebral Cortex, Cingulate Cortex, Software Tools, Radiology and Imaging, lcsh:R, Age Factors, Biology and Life Sciences, Brain, Software Engineering, Neurodegenerative Diseases, Demyelinating Disorders, Magnetic Resonance Imaging, Frontal Lobe, Neurology, Case-Control Studies, Lesions, Engineering and Technology, Clinical Immunology, Female, lcsh:Q, Clinical Medicine, Anatomy, Zoology, Software, Research Article
Abstract

The cerebral cortex is a highly folded outer layer of grey matter tissue that plays a key role in cognitive functions. In part, alterations of the cortex during development and disease can be captured by measuring the cortical thickness across the whole brain. Available software tools differ with regard to labor intensity and computational demands. In this study, we compared the computational anatomy toolbox (CAT), a recently proposed volume-based tool, with the well-established surface-based tool FreeSurfer. We observed that overall thickness measures were highly inter-correlated, although thickness estimates were systematically lower in CAT than in FreeSurfer. Comparison of multiple sclerosis (MS) patients with age-matched healthy control subjects showed highly comparable clusters of MS-related thinning for both methods. Likewise, both methods yielded comparable clusters of age-related cortical thinning, although correlations between age and average cortical thickness were stronger for FreeSurfer. Our data suggest that, for the analysis of cortical thickness, the volume-based CAT tool can be regarded a considerable alternative to the well-established surface-based FreeSurfer tool.

Published
2017

25. Suicidal ideation in a European Huntington's disease population

Author

Hubers, Aa, van Duijn, E, Roos, Ra, Craufurd, D, Rickards, H, Bernhard Landwehrmeyer, G, van der Mast RC, Giltay, Ej, Bachoud Lévi AC, Bentivoglio, Ar, Biunno, I, Bonelli, Rm, Burgunder, Jm, Dunnett, Sb, Ferreira, Jj, Handley, Oj, Heiberg, A, Llmann, Ti, Landwehrmeyer, Gb, Levey, J, Ramos Arroyo MA, Nielsen, Je, Prokoivisto, S, Päivärinta, M, Rojo Sebastián, A, Tabrizi, Sj, Vandenberghe, W, Verellen Dumoulin, C, Zaremba, J, Uhrova, T, Wahlström, J, Barth, K, Correia Guedes, L, Finisterra, Am, Garde, Mb, Bos, R, Betz, S, Callaghan, J, Fullam, R, Ecker, D, Nielsen, Mg, Hvalstedt, C, Held, C, Koppers, K, Laurà, M, Horta, Sm, Descals, Am, Mestre, T, Minster, S, Monza, D, Mütze, L, Oehmen, M, Townhill, J, Orth, M, Padieu, H, Paterski, L, Peppa, N, Pro Koivisto, S, Roedig, V, Rialland, A, Røren, N, Šašinková, P, Seliverstov, Y, Cubillo, Pt, Walsem, Mr, Wright, A, da Silva WV, Witjes Ané MN, Yudina, E, Zielonka, D, Zielonka, E, Zinzi, P, Herranhof, B, Holl, A, Kapfhammer, Hp, Koppitz, M, Magnet, M, Otti, D, Painold, A, Reisinger, K, Scheibl, M, Hecht, K, Lilek, S, Müller, N, Schöggl, H, Ullah, J, Brugger, F, Hepperger, C, Hotter, A, Seppi, K, Wenning, G, Buratti, L, Hametner, Em, Holas, C, Hussl, A, Poewe, W, Braunwarth, Em, Sprenger, F, Müller, C, Sinadinosa, D, Walleczek, Am, Ladurner, G, Staffen, W, Flamez, A, Morez, V, de Raedt, S, Boogaerts, A, van Reijen, D, Klempíř, J, Majerová, V, Roth, J, Hartikainen, P, Hiivola, H, Martikainen, K, Tuuha, K, Ignatius, J, Kärppä, M, Åman, J, Mustonen, A, Kajula, O, Santala, M, Allain, P, Guérid, Ma, Gohier, B, Olivier, A, Prundean, A, Scherer Gagou, C, Verny, C, Bost, M, Babiloni, B, Debruxelles, S, Duché, C, Goizet, C, Lafoucrière, D, Jameau, L, Spampinato, U, De Bruycker, C, Cabaret, M, Carette, As, Defebvre, L, Decorte, E, Delval, A, Delliaux, M, Destee, A, Dujardin, K, Peter, M, Plomhouse, L, Sablonnière, B, Simonin, C, Lemaire, Mh, Manouvrier, S, Thibault Tanchou, S, Vuillaume, I, Krystkowiak, P, Duru, C, Roussel, M, Wannepain, S, Berrissoul, H, Bellonet, M, Courtin, F, Mantaux, B, Fasquel, V, Godefroy, O, Azulay, Jp, Fluchère, F, Delfini, M, Eusebio, A, Mundler, L, Longato, N, Rudolf, G, Steinmetz, G, Tranchant, C, Wagner, C, Zimmermann, M, Marcel, C, Calvas, F, Pariente, J, Démonet, Jf, Cheriet, S, Kosinski, Cm, Milkereit, E, Probst, D, Reetz, K, Sass, C, Schiefer, J, Schlangen, C, Werner, Cj, Gelderblom, H, Priller, J, Prüß, H, Spruth, Ej, Andrich, J, Ellrichmann, G, Hoffmann, R, Kaminski, B, Saft, C, Stamm, C, Lange, H, Bosredon, C, Maass, A, Schmidt, S, Storch, A, Wolz, M, Kohl, Z, Winkler, J, Capetian, P, Lambeck, J, Zucker, B, Boelmans, K, Ganos, C, Goerendt, I, Hidding, U, Lewerenz, J, Münchau, A, Schmalfeld, J, Stubbe, L, Zittel, S, Diercks, G, Dressler, D, Gorzolla, H, Schrader, C, Tacik, P, Heinicke, W, Longinus, B, Bürk, K, Möller, Jc, Rissling, I, Mühlau, M, Peinemann, A, Städtler, M, Weindl, A, Winkelmann, J, Ziegler, C, Bohlen, S, Hölzner, E, Reilmann, R, Dose, M, Leythaeuser, G, Marquard, R, Raab, T, Schrenk, C, Schuierer, M, Buck, A, Connemann, J, Eschenbach, C, Landwehrmeyer, B, Lezius, F, Nepper, S, Niess, A, Schwenk, D, Süßmuth, S, Trautmann, S, Weydt, P, Cormio, C, Sciruicchio, V, Serpino, C, Tommaso, M, Capellari, S, Cortelli, P, Gallassi, R, Poda, R, Rizzo, G, Scaglione, C, Bertini, E, Ghelli, E, Ginestroni, A, Massaro, F, Mechi, C, Paganini, M, Piacentini, S, Pradella, S, Romoli, Am, Sorbi, S, Abbruzzese, G, di Poggio MB, Di Maria, E, Ferrandes, G, Mandich, P, Marchese, R, Albanese, A, Di Bella, D, Di Donato, S, Gellera, C, Genitrini, S, Mariotti, C, Nanetti, L, Paridi, D, Soliveri, P, Tomasello, C, De Michele, G, Di Maio, L, Salvatore, E, Rinaldi, C, Rossi, F, Massarelli, M, Roca, A, Ammendola, S, Russo, Cv, Squitieri, F, Elifani, F, Maglione, V, Di Pardo, A, Alberti, S, Griguoli, A, Amico, E, Martino, T, Petrollini, M, Catalli, C, Di Giacopo, R, Fasano, A, Frontali, M, Guidubaldi, A, Ialongo, T, Jacopini, G, Loria, G, Piano, C, Chiara, P, Quaranta, D, Romano, Silvia, Soleti, F, Spadaro, M, Romano, S, van Hout MS, van Vugt JP, Weert, A, Bolwijn, J, Dekker, M, Leenders, K, Kremer, Hp, Dumas, Em, van den Bogaard SJ, 't Hart EP, Økland, E, Hauge, E, Tyvoll, H, Frich, J, Aaserud, O, Wehus, R, Bjørgo, K, Fannemel, M, Gørvell, P, Lorentzen, E, Koivisto, Sp, Retterstøl, L, Overland, T, Stokke, B, Sando, B, Dziadkiewicz, A, Nowak, M, Robowski, P, Sitek, E, Slawek, J, Soltan, W, Szinwelski, M, Blaszcyk, M, Boczarska Jedynak, M, Ciach Wysocka, E, Gorzkowska, A, Jasinska Myga, B, Opala, G, Kłodowska Duda, G, Stompel, D, Banaszkiewicz, K, Boćwińska, D, Szczudlik, A, Rudzińska, M, Wójcik, M, Dec, M, Krawczyk, M, Jaremek, Kb, Szczygieł, E, Stenwak, A, Ielewska, Aw, Bryl, A, Ciesielska, A, Klimberg, A, Marcinkowski, J, Sempołowicz, J, Samara, H, Wiśniewski, B, Janik, P, Gogol, A, Kwiecinski, H, Jamrozik, Z, Kaminska, A, Antczak, J, Jachinska, K, Rakowicz, M, Richter, P, Rola, R, Ryglewicz, D, Sienkiewicz Jarosz, H, Stępniak, I, Witkowski, G, Zdzienicka, E, Sułek, A, Krysa, W, Zieora Jakutowicz, K, Júlio, F, Januário, C, Coelho, M, Mendes, T, Valadas, A, Timóteo, Â, Costa, C, Cavaco, S, Damásio, J, Loureiro, R, Magalhães, M, Andrade, C, Gago, M, Garrett, C, Guerra, Mr, Lima, J, Massano, J, Meireles, J, Herrera, Cd, Garcia, Pm, Barrero, F, Morales, B, Cubo, E, Mariscal, N, Sánchez, J, Alonso Frech, F, Perez, Mr, Fenollar, M, García, Rg, Quiroga, Pp, Rivera, Sv, Villanueva, C, Alegre, J, Bascuñana, M, Caldentey, Jg, Ventura, Mf, Ribas, Gg, Yébenes, Jg, López Sendón Moreno JL, García Ruíz PJ, Martínez Descals, A, Artiga, Mj, Sánchez, V, Guerrero, R, Bárcenas, Ah, Noguera Perea MF, Fortuna, L, Martirio, M, Torres, A, Reinante, G, Moreau, Lv, Barbera, Ma, Guia, Db, Hernanz, Lc, Catena, Jl, Sebastián, Ar, Ferrer, Pq, Carruesco, Gt, Bas, J, Busquets, N, Calopa, M, Elorza, Md, Díez AjaLópez, C, Terol, Sd, Robert, Mf, Ruíz, Bg, Casado, Ag, Martínez, Ih, Viladrich, Cm, Càrdenas, Rp, Roca, E, Llesoy, Jr, Idiago, Jm, Vergara, Mr, García, Ss, Riballo, Av, González, Sg, Guisasola, Lm, Salvador, C, San Martín ES, González, M, Gorospe, A, Legarda, I, Arques, Pn, Torres Rodríguez MJ, Vives, B, Gaston, I, Martinez Jaurrieta MD, Manuel, J, Moreno, G, Peña, Jc, Avarvarei, Ld, Bastida, Am, Recio, Mf, Vergé, Lr, Sánchez, Vs, Carrillo, F, Cáceres, Mt, Mir, P, Suarez, Mj, Bosca, M, Burguera, Ja, Garcia, Ac, Brugada, Fc, Martínez, Lm, Val, Jl, Loutfi, G, Olofsson, C, Stattin, El, Westman, L, Wikström, B, Lhagen, Se, Paucar, M, Svenningsson, P, Reza Soltani TW, Höglund, A, Sandström, B, Høsterey Ugander, U, Fredlund, G, Constantinescu, R, Neleborn Lingefjärd, L, Tedr off, J, Esmaeilzadeh, M, Winnberg, E, Pålhagen, S, Svennigsson, P, Riza Soltani TW, Sundblom, J, Johansson, A, Wiklund, L, Ekwall, C, Göller, Ml, Petersén, A, Reimer, J, Widner, H, Stebler, Y, Kaelin, A, Romero, I, Schüpbach, M, Weber, S, Miedzybrodzka, Z, Rae, D, Downie, L, Simpson, S, Summers, F, Ure, A, Jack, R, Matheson, K, Akhtar, S, Crooks, J, Curtis, A, Souza, J, Wright, J, Hayward, B, Sieradzan, K, Barker, Ra, O'Keefe, D, Di Pietro, A, Fisher, K, Hill, S, Mason, S, Swain, R, Valle, N, Guzman, Bisson, J, Busse, M, Butcher, C, Clenaghan, C, Dunnett, S, Handley, O, Hunt, S, Hughes, A, Johnstone, C, Jones, L, Jones, U, Khalil, H, Owen, M, Price, K, Rose, Le, Rosser, A, Porteous, M, Edwards, M, Ho, C, Mcgill, M, Pearson, P, Brockie, P, Foster, J, Johns, N, Mckenzie, S, Rothery, J, Thomas, G, Yates, S, Miller, J, Ritchie, S, Burrows, L, Fletcher, A, Harding, A, Laver, F, Silva, M, Thomson, A, Rowett, L, Gallantrae, D, Longthorpe, M, Markova, I, Raman, A, Hamer, S, Wild, S, Yarduiman, P, Chu, C, Kraus, A, Yardumian, P, Musgrave, H, Toscano, J, Jamieson, S, Hobson, E, Clayton, C, Dipple, H, Middleton, J, Freire Patino, D, Andrews, T, Dougherty, A, Kavalier, F, Golding, C, Laing, H, Lashwood, A, Robertson, D, Ruddy, D, Whaite, A, Santhouse, A, Patton, M, Peterson, M, Rose, S, Bruno, S, Chu, E, Doherty, K, Haider, S, Hensman, D, Lahiri, N, Lewis, M, Novak, M, Patel, A, Robertson, N, Rosser, E, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Howard, L, Sollom, A, Snowden, J, Thompson, J, Jones, M, Murphy, H, Trender Gerhard, I, Rogers, D, Bek, J, Oughton, E, Johnson, L, Hare, M, Arran, N, Verstraelen, N, Partington Jones, L, Huson, S, Stopford, C, Westmoreland, L, Davidson, J, Morgan, K, Savage, L, Singh, B, Komati, S, Nemeth, Ah, Armstrong, R, Valentine, R, Siuda, G, Harrison, D, Hughes, M, Parkinson, A, Soltysiak, B, Burn, J, Coleman, C, Bandmann, O, Bradbury, A, Gill, P, Fairtlough, H, Fillingham, K, Foustanos, I, Kazoka, M, O'Donovan, K, Taylor, C, Tidswell, K, Quarrell, O., Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), A. A., M, E. v., Duijn, R. A., C, D., Craufurd, H., Rickard, G. B., Landwehrmeyer, R. C., Van, E. J., Giltay, R. E., G., Rinaldi, Carlo, Anna A.M. Huber, Erik van Duijn, Raymund A.C. Roo, David Craufurd, Hugh Rickard, G. Bernhard Landwehrmeyer, Rose C. van der Mast, Erik J. Giltay REGISTRY investigators of the European Huntington's Disease Network. Collaborators: Bachoud-Lévi AC, Bentivoglio AR, Biunno I, Bonelli RM, Burgunder JM, Dunnett SB, Ferreira JJ, Handley OJ, Heiberg A, llmann TI, Landwehrmeyer GB, Levey J, Ramos-Arroyo MA, Nielsen JE, ProKoivisto S, Päivärinta M, Roos RA, Rojo Sebastián A, Tabrizi SJ, Vandenberghe W, Verellen- Dumoulin C, Zaremba J, Uhrova T, Wahlström J, Barth K, Correia-Guedes L, Finisterra AM, Garde MB, Bos R, Betz S, Callaghan J, Fullam R, Ecker D, Nielsen MG, Hvalstedt C, Held C, Koppers K, Laurà M, Horta SM, Descals AM, Mestre T, Minster S, Monza D, Mütze L, Oehmen M, Townhill J, Orth M, Padieu H, Paterski L, Peppa N, Pro Koivisto S, Roedig V, Rialland A, Røren N, Šašinková P, Seliverstov Y, Cubillo PT, Walsem MR, Wright A, da Silva WV, Witjes-Ané MN, Yudina E, Zielonka D, Zielonka E, Zinzi P, Herranhof B, Holl A, Kapfhammer HP, Koppitz M, Magnet M, Otti D, Painold A, Reisinger K, Scheibl M, Hecht K, Lilek S, Müller N, Schöggl H, Ullah J, Brugger F, Hepperger C, Hotter A, Seppi K, Wenning G, Buratti L, Hametner EM, Holas C, Hussl A, Poewe W, Braunwarth EM, Sprenger F, Müller C, Sinadinosa D, Walleczek AM, Ladurner G, Staffen W, Flamez A, Morez V, de Raedt S, Boogaerts A, van Reijen D, Klempíř J, Majerová V, Roth J, Hartikainen P, Hiivola H, Martikainen K, Tuuha K, Ignatius J, Kärppä M, Åman J, Mustonen A, Kajula O, Santala M, Allain P, Guérid MA, Gohier B, Olivier A, Prundean A, Scherer- Gagou C, Verny C, Bost M, Babiloni B, Debruxelles S, Duché C, Goizet C, Lafoucrière D, Jameau L, Spampinato U, De Bruycker C, Cabaret M, Carette AS, Defebvre L, Decorte E, Delval A, Delliaux M, Destee A, Dujardin K, Peter M, Plomhouse L, Sablonnière B, Simonin C, Lemaire MH, Manouvrier S, Thibault-Tanchou S, Vuillaume I, Krystkowiak P, Duru C, Roussel M, Wannepain S, Berrissoul H, Bellonet M, Courtin F, Mantaux B, Fasquel V, Godefroy O, Azulay JP, Fluchère F, Delfini M, Eusebio A, Mundler L, Longato N, Rudolf G, Steinmetz G, Tranchant C, Wagner C, Zimmermann M, Marcel C, Calvas F, Pariente J, Démonet JF, Cheriet S, Kosinski CM, Milkereit E, Probst D, Reetz K, Sass C, Schiefer J, Schlangen C, Werner CJ, Gelderblom H, Priller J, Prüß H, Spruth EJ, Andrich J, Ellrichmann G, Hoffmann R, Kaminski B, Saft C, Stamm C, Lange H, Bosredon C, Maass A, Schmidt S, Storch A, Wolz M, Kohl Z, Winkler J, Capetian P, Lambeck J, Zucker B, Boelmans K, Ganos C, Goerendt I, Hidding U, Lewerenz J, Münchau A, Schmalfeld J, Stubbe L, Zittel S, Diercks G, Dressler D, Gorzolla H, Schrader C, Tacik P, Heinicke W, Longinus B, Bürk K, Möller JC, Rissling I, Mühlau M, Peinemann A, Städtler M, Weindl A, Winkelmann J, Ziegler C, Bohlen S, Hölzner E, Reilmann R, Dose M, Leythaeuser G, Marquard R, Raab T, Schrenk C, Schuierer M, Buck A, Connemann J, Eschenbach C, Landwehrmeyer B, Lezius F, Nepper S, Niess A, Schwenk D, Süßmuth S, Trautmann S, Weydt P, Cormio C, Sciruicchio V, Serpino C, Tommaso M, Capellari S, Cortelli P, Gallassi R, Poda R, Rizzo G, Scaglione C, Bertini E, Ghelli E, Ginestroni A, Massaro F, Mechi C, Paganini M, Piacentini S, Pradella S, Romoli AM, Sorbi S, Abbruzzese G, di Poggio MB, Di Maria E, Ferrandes G, Mandich P, Marchese R, Albanese A, Di Bella D, Di Donato S, Gellera C, Genitrini S, Mariotti C, Nanetti L, Paridi D, Soliveri P, Tomasello C, De Michele G, Di Maio L, Salvatore E, Rinaldi C, Rossi F, Massarelli M, Roca A, Ammendola S, Russo CV, Squitieri F, Elifani F, Maglione V, Di Pardo A, Alberti S, Griguoli A, Amico E, Martino T, Petrollini M, Catalli C, Di Giacopo R, Fasano A, Frontali M, Guidubaldi A, Ialongo T, Jacopini G, Loria G, Piano C, Chiara P, Quaranta D, Romano S, Soleti F, Spadaro M, van Hout MS, van Vugt JP, Weert A, Bolwijn J, Dekker M, Leenders K, Kremer HP, Dumas EM, van den Bogaard SJ, 't Hart EP, van Duijn E, Økland E, Hauge E, Tyvoll H, Frich J, Aaserud O, Wehus R, Bjørgo K, Fannemel M, Gørvell P, Lorentzen E, Koivisto SP, Retterstøl L, Overland T, Stokke B, Sando B, Dziadkiewicz A, Nowak M, Robowski P, Sitek E, Slawek J, Soltan W, Szinwelski M, Blaszcyk M, Boczarska-Jedynak M, Ciach-Wysocka E, Gorzkowska A, Jasinska-Myga B, Opala G, Kłodowska-Duda G, Stompel D, Banaszkiewicz K, Boćwińska D, Szczudlik A, Rudzińska M, Wójcik M, Dec M, Krawczyk M, Jaremek KB, Szczygieł E, Stenwak A, ielewska AW, Bryl A, Ciesielska A, Klimberg A, Marcinkowski J, Sempołowicz J, Samara H, Wiśniewski B, Janik P, Gogol A, Kwiecinski H, Jamrozik Z, Kaminska A, Antczak J, Jachinska K, Rakowicz M, Richter P, Rola R, Ryglewicz D, Sienkiewicz-Jarosz H, Stępniak I, Witkowski G, Zdzienicka E, Sułek A, Krysa W, Zieora-Jakutowicz K, Júlio F, Januário C, Coelho M, Mendes T, Valadas A, Timóteo Â, Costa C, Cavaco S, Damásio J, Loureiro R, Magalhães M, Andrade C, Gago M, Garrett C, Guerra MR, Lima J, Massano J, Meireles J, Herrera CD, Garcia PM, Barrero F, Morales B, Cubo E, Mariscal N, Sánchez J, Alonso-Frech F, Perez MR, Fenollar M, García RG, Quiroga PP, Rivera SV, Villanueva C, Alegre J, Bascuñana M, Caldentey JG, Ventura MF, Ribas GG, Yébenes JG, López-Sendón Moreno JL, García Ruíz PJ, Martínez-Descals A, Artiga MJ, Sánchez V, Guerrero R, Bárcenas AH, Noguera Perea MF, Fortuna L, Martirio M, Torres A, Reinante G, Moreau LV, Barbera MA, Guia DB, Hernanz LC, Catena JL, Sebastián AR, Ferrer PQ, Carruesco GT, Bas J, Busquets N, Calopa M, Elorza MD, Díez-AjaLópez C, Terol SD, Robert MF, Ruíz BG, Casado AG, Martínez IH, Viladrich CM, Càrdenas RP, Roca E, Llesoy JR, Idiago JM, Vergara MR, García SS, Riballo AV, González SG, Guisasola LM, Salvador C, San Martín ES, González M, Gorospe A, Legarda I, Arques PN, Torres Rodríguez MJ, Vives B, Gaston I, Martinez-Jaurrieta MD, Manuel J, Moreno G, Peña JC, Avarvarei LD, Bastida AM, Recio MF, Vergé LR, Sánchez VS, Carrillo F, Cáceres MT, Mir P, Suarez MJ, Bosca M, Burguera JA, Garcia AC, Brugada FC, Martínez LM, Val JL, Loutfi G, Olofsson C, Stattin EL, Westman L, Wikström B, lhagen SE, Paucar M, Svenningsson P, Reza- Soltani TW, Höglund A, Sandström B, Høsterey-Ugander U, Fredlund G, Constantinescu R, Neleborn-Lingefjärd L, Tedr- off J, Esmaeilzadeh M, Winnberg E, Pålhagen S, Svennigsson P, Riza-Soltani TW, Sundblom J, Johansson A, Wiklund L, Ekwall C, Göller ML, Petersén A, Reimer J, Widner H, Stebler Y, Kaelin A, Romero I, Schüpbach M, Weber S, Miedzybrodzka Z, Rae D, Downie L, Simpson S, Summers F, Ure A, Jack R, Matheson K, Akhtar S, Crooks J, Curtis A, Souza J, Rickards H, Wright J, Hayward B, Sieradzan K, Barker RA, O'Keefe D, Di Pietro A, Fisher K, Hill S, Mason S, Swain R, Valle N, Guzman, Bisson J, Busse M, Butcher C, Clenaghan C, Dunnett S, Handley O, Hunt S, Hughes A, Johnstone C, Jones L, Jones U, Khalil H, Owen M, Price K, Rose LE, Rosser A, Porteous M, Edwards M, Ho C, McGill M, Pearson P, Brockie P, Foster J, Johns N, McKenzie S, Rothery J, Thomas G, Yates S, Miller J, Ritchie S, Burrows L, Fletcher A, Harding A, Laver F, Silva M, Thomson A, Rowett L, Gallantrae D, Longthorpe M, Markova I, Raman A, Hamer S, Wild S, Yarduiman P, Chu C, Kraus A, Yardumian P, Musgrave H, Toscano J, Jamieson S, Hobson E, Clayton C, Dipple H, Middleton J, Freire-Patino D, Andrews T, Dougherty A, Kavalier F, Golding C, Laing H, Lashwood A, Robertson D, Ruddy D, Whaite A, Santhouse A, Patton M, Peterson M, Rose S, Bruno S, Chu E, Doherty K, Haider S, Hensman D, Lahiri N, Lewis M, Novak M, Patel A, Robertson N, Rosser E, Tabrizi S, Taylor R, Warner T, Wild E, Craufurd D, Howard L, Sollom A, Snowden J, Thompson J, Jones M, Murphy H, Trender-Gerhard I, Rogers D, Bek J, Oughton E, Johnson L, Hare M, Arran N, Verstraelen N, Partington-Jones L, Huson S, Stopford C, Westmoreland L, Davidson J, Morgan K, Savage L, Singh B, Komati S, Nemeth AH, Armstrong R, Valentine R, Siuda G, Harrison D, Hughes M, Parkinson A, Soltysiak B, Burn J, Coleman C, Bandmann O, Bradbury A, Gill P, Fairtlough H, Fillingham K, Foustanos I, Kazoka M, O'Donovan K, Taylor C, Tidswell K, Quarrell O., Molecular Neuroscience and Ageing Research (MOLAR), Hubers, Aa, van Duijn, E, Roos, Ra, Craufurd, D, Rickards, H, Bernhard Landwehrmeyer, G, van der Mast, Rc, Giltay, Ej, CollaboratorsBachoud Lévi AC, REGISTRY investigators of the European Huntington's Disease N. e. t. w. o. r. k., Bentivoglio, Ar, Biunno, I, Bonelli, Rm, Burgunder, Jm, Dunnett, Sb, Ferreira, Jj, Handley, Oj, Heiberg, A, Llmann, Ti, Landwehrmeyer, Gb, Levey, J, Ramos Arroyo, Ma, Nielsen, Je, Prokoivisto, S, Päivärinta, M, Rojo Sebastián, A, Tabrizi, Sj, Vandenberghe, W, Verellen Dumoulin, C, Zaremba, J, Uhrova, T, Wahlström, J, Barth, K, Correia Guedes, L, Finisterra, Am, Garde, Mb, Bos, R, Betz, S, Callaghan, J, Fullam, R, Ecker, D, Nielsen, Mg, Hvalstedt, C, Held, C, Koppers, K, Laurà, M, Horta, Sm, Descals, Am, Mestre, T, Minster, S, Monza, D, Mütze, L, Oehmen, M, Townhill, J, Orth, M, Padieu, H, Paterski, L, Peppa, N, Pro Koivisto, S, Roedig, V, Rialland, A, Røren, N, a??inková, P, Seliverstov, Y, Cubillo, Pt, Walsem, Mr, Wright, A, da Silva, Wv, Witjes Ané, Mn, Yudina, E, Zielonka, D, Zielonka, E, Zinzi, P, Herranhof, B, Holl, A, Kapfhammer, Hp, Koppitz, M, Magnet, M, Otti, D, Painold, A, Reisinger, K, Scheibl, M, Hecht, K, Lilek, S, Müller, N, Schöggl, H, Ullah, J, Brugger, F, Hepperger, C, Hotter, A, Seppi, K, Wenning, G, Buratti, L, Hametner, Em, Holas, C, Hussl, A, Poewe, W, Braunwarth, Em, Sprenger, F, Müller, C, Sinadinosa, D, Walleczek, Am, Ladurner, G, Staffen, W, Flamez, A, Morez, V, de Raedt, S, Boogaerts, A, van Reijen, D, Klempí??, J, Majerová, V, Roth, J, Hartikainen, P, Hiivola, H, Martikainen, K, Tuuha, K, Ignatius, J, Kärppä, M, Åman, J, Mustonen, A, Kajula, O, Santala, M, Allain, P, Guérid, Ma, Gohier, B, Olivier, A, Prundean, A, Scherer Gagou, C, Verny, C, Bost, M, Babiloni, B, Debruxelles, S, Duché, C, Goizet, C, Lafoucrière, D, Jameau, L, Spampinato, U, De Bruycker, C, Cabaret, M, Carette, A, Defebvre, L, Decorte, E, Delval, A, Delliaux, M, Destee, A, Dujardin, K, Peter, M, Plomhouse, L, Sablonnière, B, Simonin, C, Lemaire, Mh, Manouvrier, S, Thibault Tanchou, S, Vuillaume, I, Krystkowiak, P, Duru, C, Roussel, M, Wannepain, S, Berrissoul, H, Bellonet, M, Courtin, F, Mantaux, B, Fasquel, V, Godefroy, O, Azulay, Jp, Fluchère, F, Delfini, M, Eusebio, A, Mundler, L, Longato, N, Rudolf, G, Steinmetz, G, Tranchant, C, Wagner, C, Zimmermann, M, Marcel, C, Calvas, F, Pariente, J, Démonet, Jf, Cheriet, S, Kosinski, Cm, Milkereit, E, Probst, D, Reetz, K, Sass, C, Schiefer, J, Schlangen, C, Werner, Cj, Gelderblom, H, Priller, J, Prüß, H, Spruth, Ej, Andrich, J, Ellrichmann, G, Hoffmann, R, Kaminski, B, Saft, C, Stamm, C, Lange, H, Bosredon, C, Maass, A, Schmidt, S, Storch, A, Wolz, M, Kohl, Z, Winkler, J, Capetian, P, Lambeck, J, Zucker, B, Boelmans, K, Ganos, C, Goerendt, I, Hidding, U, Lewerenz, J, Münchau, A, Schmalfeld, J, Stubbe, L, Zittel, S, Diercks, G, Dressler, D, Gorzolla, H, Schrader, C, Tacik, P, Heinicke, W, Longinus, B, Bürk, K, Möller, Jc, Rissling, I, Mühlau, M, Peinemann, A, Städtler, M, Weindl, A, Winkelmann, J, Ziegler, C, Bohlen, S, Hölzner, E, Reilmann, R, Dose, M, Leythaeuser, G, Marquard, R, Raab, T, Schrenk, C, Schuierer, M, Buck, A, Connemann, J, Eschenbach, C, Landwehrmeyer, B, Lezius, F, Nepper, S, Niess, A, Schwenk, D, Süßmuth, S, Trautmann, S, Weydt, P, Cormio, C, Sciruicchio, V, Serpino, C, Tommaso, M, Capellari, S, Cortelli, P, Gallassi, R, Poda, R, Rizzo, G, Scaglione, C, Bertini, E, Ghelli, E, Ginestroni, A, Massaro, F, Mechi, C, Paganini, M, Piacentini, S, Pradella, S, Romoli, Am, Sorbi, S, Abbruzzese, G, di Poggio, Mb, Di Maria, E, Ferrandes, G, Mandich, P, Marchese, R, Albanese, A, Di Bella, D, Di Donato, S, Gellera, C, Genitrini, S, Mariotti, C, Nanetti, L, Paridi, D, Soliveri, P, Tomasello, C, DE MICHELE, Giuseppe, Di Maio, L, Salvatore, Elena, Rossi, F, Massarelli, Marco, Roca, Alessandro, Ammendola, S, Russo, Cinzia, Squitieri, F, Elifani, F, Maglione, V, Di Pardo, A, Alberti, S, Griguoli, A, Amico, E, Martino, T, Petrollini, M, Catalli, C, Di Giacopo, R, Fasano, A, Frontali, M, Guidubaldi, A, Ialongo, T, Jacopini, G, Loria, G, Piano, C, Chiara, P, Quaranta, D, Romano, S, Soleti, F, Spadaro, M, Rinaldi, C, Massarelli, M, Roca, A, Russo, Cv, van Hout, M, van Vugt, Jp, Weert, A, Bolwijn, J, Dekker, M, Leenders, K, Kremer, Hp, Dumas, Em, van den Bogaard, Sj, 't Hart, Ep, Økland, E, Hauge, E, Tyvoll, H, Frich, J, Aaserud, O, Wehus, R, Bjørgo, K, Fannemel, M, Gørvell, P, Lorentzen, E, Koivisto, Sp, Retterstøl, L, Overland, T, Stokke, B, Sando, B, Dziadkiewicz, A, Nowak, M, Robowski, P, Sitek, E, Slawek, J, Soltan, W, Szinwelski, M, Blaszcyk, M, Boczarska Jedynak, M, Ciach Wysocka, E, Gorzkowska, A, Jasinska Myga, B, Opala, G, K??odowska Duda, G, Stompel, D, Banaszkiewicz, K, Bo??wi??ska, D, Szczudlik, A, Rudzi??ska, M, Wójcik, M, Dec, M, Krawczyk, M, Jaremek, Kb, Szczygie??, E, Stenwak, A, Ielewska, Aw, Bryl, A, Ciesielska, A, Klimberg, A, Marcinkowski, J, Sempo??owicz, J, Samara, H, Wi??niewski, B, Janik, P, Gogol, A, Kwiecinski, H, Jamrozik, Z, Kaminska, A, Antczak, J, Jachinska, K, Rakowicz, M, Richter, P, Rola, R, Ryglewicz, D, Sienkiewicz Jarosz, H, St??pniak, I, Witkowski, G, Zdzienicka, E, Su??ek, A, Krysa, W, Zieora Jakutowicz, K, Júlio, F, Januário, C, Coelho, M, Mendes, T, Valadas, A, Timóteo, Â, Costa, C, Cavaco, S, Damásio, J, Loureiro, R, Magalhães, M, Andrade, C, Gago, M, Garrett, C, Guerra, Mr, Lima, J, Massano, J, Meireles, J, Herrera, Cd, Garcia, Pm, Barrero, F, Morales, B, Cubo, E, Mariscal, N, Sánchez, J, Alonso Frech, F, Perez, Mr, Fenollar, M, García, Rg, Quiroga, Pp, Rivera, Sv, Villanueva, C, Alegre, J, Bascuñana, M, Caldentey, Jg, Ventura, Mf, Ribas, Gg, Yébenes, Jg, López Sendón Moreno, Jl, García Ruíz, Pj, Martínez Descals, A, Artiga, Mj, Sánchez, V, Guerrero, R, Bárcenas, Ah, Noguera Perea, Mf, Fortuna, L, Martirio, M, Torres, A, Reinante, G, Moreau, Lv, Barbera, Ma, Guia, Db, Hernanz, Lc, Catena, Jl, Sebastián, Ar, Ferrer, Pq, Carruesco, Gt, Bas, J, Busquets, N, Calopa, M, Elorza, Md, Díez AjaLópez, C, Terol, Sd, Robert, Mf, Ruíz, Bg, Casado, Ag, Martínez, Ih, Viladrich, Cm, Càrdenas, Rp, Roca, E, Llesoy, Jr, Idiago, Jm, Vergara, Mr, García, S, Riballo, Av, González, Sg, Guisasola, Lm, Salvador, C, San Martín, E, González, M, Gorospe, A, Legarda, I, Arques, Pn, Torres Rodríguez, Mj, Vives, B, Gaston, I, Martinez Jaurrieta, Md, Manuel, J, Moreno, G, Peña, Jc, Avarvarei, Ld, Bastida, Am, Recio, Mf, Vergé, Lr, Carrillo, F, Cáceres, Mt, Mir, P, Suarez, Mj, Bosca, M, Burguera, Ja, Garcia, Ac, Brugada, Fc, Martínez, Lm, Val, Jl, Loutfi, G, Olofsson, C, Stattin, El, Westman, L, Wikström, B, Lhagen, Se, Paucar, M, Svenningsson, P, Reza Soltani, Tw, Höglund, A, Sandström, B, Høsterey Ugander, U, Fredlund, G, Constantinescu, R, Neleborn Lingefjärd, L, Tedr off, J, Esmaeilzadeh, M, Winnberg, E, Pålhagen, S, Svennigsson, P, Riza Soltani, Tw, Sundblom, J, Johansson, A, Wiklund, L, Ekwall, C, Göller, Ml, Petersén, A, Reimer, J, Widner, H, Stebler, Y, Kaelin, A, Romero, I, Schüpbach, M, Weber, S, Miedzybrodzka, Z, Rae, D, Downie, L, Simpson, S, Summers, F, Ure, A, Jack, R, Matheson, K, Akhtar, S, Crooks, J, Curtis, A, Souza, J, Wright, J, Hayward, B, Sieradzan, K, Barker, Ra, O'Keefe, D, Di Pietro, A, Fisher, K, Hill, S, Mason, S, Swain, R, Valle, N, Bisson, J, Busse, M, Butcher, C, Clenaghan, C, Dunnett, S, Handley, O, Hunt, S, Hughes, A, Johnstone, C, Jones, L, Jones, U, Khalil, H, Owen, M, Price, K, Rose, Le, Rosser, A, Porteous, M, Edwards, M, Ho, C, Mcgill, M, Pearson, P, Brockie, P, Foster, J, Johns, N, Mckenzie, S, Rothery, J, Thomas, G, Yates, S, Miller, J, Ritchie, S, Burrows, L, Fletcher, A, Harding, A, Laver, F, Silva, M, Thomson, A, Rowett, L, Gallantrae, D, Longthorpe, M, Markova, I, Raman, A, Hamer, S, Wild, S, Yarduiman, P, Chu, C, Kraus, A, Yardumian, P, Musgrave, H, Toscano, J, Jamieson, S, Hobson, E, Clayton, C, Dipple, H, Middleton, J, Freire Patino, D, Andrews, T, Dougherty, A, Kavalier, F, Golding, C, Laing, H, Lashwood, A, Robertson, D, Ruddy, D, Whaite, A, Santhouse, A, Patton, M, Peterson, M, Rose, S, Bruno, S, Chu, E, Doherty, K, Haider, S, Hensman, D, Lahiri, N, Lewis, M, Novak, M, Patel, A, Robertson, N, Rosser, E, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Howard, L, Sollom, A, Snowden, J, Thompson, J, Jones, M, Murphy, H, Trender Gerhard, I, Rogers, D, Bek, J, Oughton, E, Johnson, L, Hare, M, Arran, N, Verstraelen, N, Partington Jones, L, Huson, S, Stopford, C, Westmoreland, L, Davidson, J, Morgan, K, Savage, L, Singh, B, Komati, S, Nemeth, Ah, Armstrong, R, Valentine, R, Siuda, G, Harrison, D, Hughes, M, Parkinson, A, Soltysiak, B, Burn, J, Coleman, C, Bandmann, O, Bradbury, A, Gill, P, Fairtlough, H, Fillingham, K, Foustanos, I, Kazoka, M, O'Donovan, K, Taylor, C, Tidswell, K, and Quarrell, O.

Subjects
Male, medicine.medical_specialty, Heterozygote, Psychopharmacology, Population, Poison control, psychology/statistics /&/ numerical data, Suicide, Attempted, Suicide prevention, Suicidal Ideation, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, medicine, Prevalence, Humans, epidemiology, Europe, Psychiatry, education, Suicidal ideation, ComputingMilieux_MISCELLANEOUS, Proportional Hazards Models, Attempted, Psychiatric Status Rating Scales, education.field_of_study, Psychological Tests, Suicide attempt, Psychopathology, Depression, Hazard ratio, Huntington's disease, Odds ratio, Middle Aged, 3. Good health, 030227 psychiatry, Europe, psychology, Male, Middle Aged, Prevalence, Proportional Hazards Models, Psychiatric Status Rating Scales, Psychological Tests, Suicidal Ideation, Suicide, Clinical Psychology, Psychiatry and Mental health, Suicide, Huntington Disease, epidemiology, Female, Heterozygote, Humans, Huntington Disease, Cohort studies, Female, medicine.symptom, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract

BACKGROUND: Previous studies indicate increased prevalences of suicidal ideation, suicide attempts, and completed suicide in Huntington's disease (HD) compared with the general population. This study investigates correlates and predictors of suicidal ideation in HD.METHODS: The study cohort consisted of 2106 HD mutation carriers, all participating in the REGISTRY study of the European Huntington's Disease Network. Of the 1937 participants without suicidal ideation at baseline, 945 had one or more follow-up measurements. Participants were assessed for suicidal ideation by the behavioural subscale of the Unified Huntington's Disease Rating Scale (UHDRS). Correlates of suicidal ideation were analyzed using logistic regression analysis and predictors were analyzed using Cox regression analysis.RESULTS: At baseline, 169 (8.0%) mutation carriers endorsed suicidal ideation. Disease duration (odds ratio [OR]=0.96; 95% confidence interval [CI]: 0.9-1.0), anxiety (OR=2.14; 95%CI: 1.4-3.3), aggression (OR=2.41; 95%CI: 1.5-3.8), a previous suicide attempt (OR=3.95; 95%CI: 2.4-6.6), and a depressed mood (OR=13.71; 95%CI: 6.7-28.0) were independently correlated to suicidal ideation at baseline. The 4-year cumulative incidence of suicidal ideation was 9.9%. Longitudinally, the presence of a depressed mood (hazard ratio [HR]=2.05; 95%CI: 1.1-4.0) and use of benzodiazepines (HR=2.44; 95%CI: 1.2-5.0) at baseline were independent predictors of incident suicidal ideation, whereas a previous suicide attempt was not predictive.LIMITATIONS: As suicidal ideation was assessed by only one item, and participants were a selection of all HD mutation carriers, the prevalence of suicidal ideation was likely underestimated.CONCLUSIONS: Suicidal ideation in HD frequently occurs. Assessment of suicidal ideation is a priority in mutation carriers with a depressed mood and in those using benzodiazepines.

Published
2013

27. Variation within the Huntington's disease gene influences normal brain structure

Author

Mühlau, M., Winkelmann, J., Rujescu, D., Giegling, I., Koutsouleris, N., Gaser, C., Arsic, M., Weindl, A., Reiser, M., and Meisenzahl, E.M.

Subjects
mental disorders, cag repeats, basal ganglia, segmentation, inference, mutation, bipolar, images, onset, mri, age
Abstract

Genetics of the variability of normal and diseased brain structure largely remains to be elucidated. Expansions of certain trinucleotide repeats cause neurodegenerative disorders of which Huntington's disease constitutes the most common example. Here, we test the hypothesis that variation within the IT15 gene on chromosome 4, whose expansion causes Huntington's disease, influences normal human brain structure. In 278 normal subjects, we determined CAG repeat length within the IT15 gene on chromosome 4 and analyzed high-resolution T1-weighted magnetic resonance images by the use of voxel-based morphometry. We found an increase of GM with increasing long CAG repeat and its interaction with age within the pallidum, which is involved in Huntington's disease. Our study demonstrates that a certain trinucleotide repeat influences normal brain structure in humans. This result may have important implications for the understanding of both the healthy and diseased brain.

Published
2012

29. Volume versus surface-based cortical thickness measurements: A comparative study with healthy controls and multiple sclerosis patients.

Author

Buck, D., Righart, R., Biberacher, V., Beer, A., Mühlau, M., Schmidt, P., Hemmer, B., Dahnke, R., Gaser, C., Kirschke, J. S., and Zimmer, C.

Subjects
CEREBRAL cortex, MULTIPLE sclerosis diagnosis, CEREBRAL cortex anatomy, CEREBRAL cortex abnormalities, MULTIPLE sclerosis treatment
Abstract

The cerebral cortex is a highly folded outer layer of grey matter tissue that plays a key role in cognitive functions. In part, alterations of the cortex during development and disease can be captured by measuring the cortical thickness across the whole brain. Available software tools differ with regard to labor intensity and computational demands. In this study, we compared the computational anatomy toolbox (CAT), a recently proposed volume-based tool, with the well-established surface-based tool FreeSurfer. We observed that overall thickness measures were highly inter-correlated, although thickness estimates were systematically lower in CAT than in FreeSurfer. Comparison of multiple sclerosis (MS) patients with age-matched healthy control subjects showed highly comparable clusters of MS-related thinning for both methods. Likewise, both methods yielded comparable clusters of age-related cortical thinning, although correlations between age and average cortical thickness were stronger for FreeSurfer. Our data suggest that, for the analysis of cortical thickness, the volume-based CAT tool can be regarded a considerable alternative to the well-established surface-based FreeSurfer tool. [ABSTRACT FROM AUTHOR]

Published
2017
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39. Structural Brain Changes in Tinnitus

Author

Mühlau, M., primary, Rauschecker, J. P., additional, Oestreicher, E., additional, Gaser, C., additional, Röttinger, M., additional, Wohlschläger, A. M., additional, Simon, F., additional, Etgen, T., additional, Conrad, B., additional, and Sander, D., additional

Published
2005
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45. Intensity scaling of conventional brain magnetic resonance images avoiding cerebral reference regions: A systematic review.

Author

Wiltgen T, Voon C, Van Leemput K, Wiestler B, and Mühlau M

Abstract

Background: Conventional brain magnetic resonance imaging (MRI) produces image intensities that have an arbitrary scale, hampering quantification. Intensity scaling aims to overcome this shortfall. As neurodegenerative and inflammatory disorders may affect all brain compartments, reference regions within the brain may be misleading. Here we summarize approaches for intensity scaling of conventional T1-weighted (w) and T2w brain MRI avoiding reference regions within the brain., Methods: Literature was searched in the databases of Scopus, PubMed, and Web of Science. We included only studies that avoided reference regions within the brain for intensity scaling and provided validating evidence, which we divided into four categories: 1) comparative variance reduction, 2) comparative correlation with clinical parameters, 3) relation to quantitative imaging, or 4) relation to histology., Results: Of the 3825 studies screened, 24 fulfilled the inclusion criteria. Three studies used scaled T1w images, 2 scaled T2w images, and 21 T1w/T2w-ratio calculation (with double counts). A robust reduction in variance was reported. Twenty studies investigated the relation of scaled intensities to different types of quantitative imaging. Statistically significant correlations with clinical or demographic data were reported in 8 studies. Four studies reporting the relation to histology gave no clear picture of the main signal driver of conventional T1w and T2w MRI sequences., Conclusions: T1w/T2w-ratio calculation was applied most often. Variance reduction and correlations with other measures suggest a biologically meaningful signal harmonization. However, there are open methodological questions and uncertainty on its biological underpinning. Validation evidence on other scaling methods is even sparser., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wiltgen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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46. LST-AI: a Deep Learning Ensemble for Accurate MS Lesion Segmentation.

Author

Wiltgen T, McGinnis J, Schlaeger S, Kofler F, Voon C, Berthele A, Bischl D, Grundl L, Will N, Metz M, Schinz D, Sepp D, Prucker P, Schmitz-Koep B, Zimmer C, Menze B, Rueckert D, Hemmer B, Kirschke J, Mühlau M, and Wiestler B

Abstract

Automated segmentation of brain white matter lesions is crucial for both clinical assessment and scientific research in multiple sclerosis (MS). Over a decade ago, we introduced an engineered lesion segmentation tool, LST. While recent lesion segmentation approaches have leveraged artificial intelligence (AI), they often remain proprietary and difficult to adopt. As an open-source tool, we present LST-AI, an advanced deep learning-based extension of LST that consists of an ensemble of three 3D-UNets. LST-AI explicitly addresses the imbalance between white matter (WM) lesions and non-lesioned WM. It employs a composite loss function incorporating binary cross-entropy and Tversky loss to improve segmentation of the highly heterogeneous MS lesions. We train the network ensemble on 491 MS pairs of T1w and FLAIR images, collected in-house from a 3T MRI scanner, and expert neuroradiologists manually segmented the utilized lesion maps for training. LST-AI additionally includes a lesion location annotation tool, labeling lesion location according to the 2017 McDonald criteria (periventricular, infratentorial, juxtacortical, subcortical). We conduct evaluations on 103 test cases consisting of publicly available data using the Anima segmentation validation tools and compare LST-AI with several publicly available lesion segmentation models. Our empirical analysis shows that LST-AI achieves superior performance compared to existing methods. Its Dice and F1 scores exceeded 0.62, outperforming LST, SAMSEG (Sequence Adaptive Multimodal SEGmentation), and the popular nnUNet framework, which all scored below 0.56. Notably, LST-AI demonstrated exceptional performance on the MSSEG-1 challenge dataset, an international WM lesion segmentation challenge, with a Dice score of 0.65 and an F1 score of 0.63-surpassing all other competing models at the time of the challenge. With increasing lesion volume, the lesion detection rate rapidly increased with a detection rate of >75% for lesions with a volume between 10mm 3 and 100mm 3 . Given its higher segmentation performance, we recommend that research groups currently using LST transition to LST-AI. To facilitate broad adoption, we are releasing LST-AI as an open-source model, available as a command-line tool, dockerized container, or Python script, enabling diverse applications across multiple platforms., Competing Interests: Declaration of Competing Interests: The authors declare no competing interests.

Published
2024
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47. Prospective study validating a multidimensional treatment decision score predicting the 24-month outcome in untreated patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis, the ProVal-MS study.

Author

Bayas A, Mansmann U, Ön BI, Hoffmann VS, Berthele A, Mühlau M, Kowarik MC, Krumbholz M, Senel M, Steuerwald V, Naumann M, Hartberger J, Kerschensteiner M, Oswald E, Ruschil C, Ziemann U, Tumani H, Vardakas I, Albashiti F, Kramer F, Soto-Rey I, Spengler H, Mayer G, Kestler HA, Kohlbacher O, Hagedorn M, Boeker M, Kuhn K, Buchka S, Kohlmayer F, Kirschke JS, Behrens L, Zimmermann H, Bender B, Sollmann N, Havla J, and Hemmer B

Abstract

Introduction: In Multiple Sclerosis (MS), patients´ characteristics and (bio)markers that reliably predict the individual disease prognosis at disease onset are lacking. Cohort studies allow a close follow-up of MS histories and a thorough phenotyping of patients. Therefore, a multicenter cohort study was initiated to implement a wide spectrum of data and (bio)markers in newly diagnosed patients., Methods: ProVal-MS (Prospective study to validate a multidimensional decision score that predicts treatment outcome at 24 months in untreated patients with clinically isolated syndrome or early Relapsing-Remitting-MS) is a prospective cohort study in patients with clinically isolated syndrome (CIS) or Relapsing-Remitting (RR)-MS (McDonald 2017 criteria), diagnosed within the last two years, conducted at five academic centers in Southern Germany. The collection of clinical, laboratory, imaging, and paraclinical data as well as biosamples is harmonized across centers. The primary goal is to validate (discrimination and calibration) the previously published DIFUTURE MS-Treatment Decision score (MS-TDS). The score supports clinical decision-making regarding the options of early (within 6 months after study baseline) platform medication (Interferon beta, glatiramer acetate, dimethyl/diroximel fumarate, teriflunomide), or no immediate treatment (> 6 months after baseline) of patients with early RR-MS and CIS by predicting the probability of new or enlarging lesions in cerebral magnetic resonance images (MRIs) between 6 and 24 months. Further objectives are refining the MS-TDS score and providing data to identify new markers reflecting disease course and severity. The project also provides a technical evaluation of the ProVal-MS cohort within the IT-infrastructure of the DIFUTURE consortium (Data Integration for Future Medicine) and assesses the efficacy of the data sharing techniques developed., Perspective: Clinical cohorts provide the infrastructure to discover and to validate relevant disease-specific findings. A successful validation of the MS-TDS will add a new clinical decision tool to the armamentarium of practicing MS neurologists from which newly diagnosed MS patients may take advantage. Trial registration ProVal-MS has been registered in the German Clinical Trials Register, `Deutsches Register Klinischer Studien` (DRKS)-ID: DRKS00014034, date of registration: 21 December 2018; https://drks.de/search/en/trial/DRKS00014034., (© 2024. The Author(s).)

Published
2024
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48. Validating a minipig model of reversible cerebral demyelination using human diagnostic modalities and electron microscopy.

Author

Ancău M, Tanti GK, Butenschoen VM, Gempt J, Yakushev I, Nekolla S, Mühlau M, Scheunemann C, Heininger S, Löwe B, Löwe E, Baer S, Fischer J, Reiser J, Ayachit SS, Liesche-Starnecker F, Schlegel J, Matiasek K, Schifferer M, Kirschke JS, Misgeld T, Lueth T, and Hemmer B

Subjects
Swine, Humans, Animals, Mice, Cuprizone, Swine, Miniature, Myelin Sheath pathology, Microscopy, Electron, Disease Models, Animal, Demyelinating Diseases diagnostic imaging, Demyelinating Diseases pathology, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis pathology, White Matter pathology
Abstract

Background: Inflammatory demyelinating diseases of the central nervous system, such as multiple sclerosis, are significant sources of morbidity in young adults despite therapeutic advances. Current murine models of remyelination have limited applicability due to the low white matter content of their brains, which restricts the spatial resolution of diagnostic imaging. Large animal models might be more suitable but pose significant technological, ethical and logistical challenges., Methods: We induced targeted cerebral demyelinating lesions by serially repeated injections of lysophosphatidylcholine in the minipig brain. Lesions were amenable to follow-up using the same clinical imaging modalities (3T magnetic resonance imaging, 11 C-PIB positron emission tomography) and standard histopathology protocols as for human diagnostics (myelin, glia and neuronal cell markers), as well as electron microscopy (EM), to compare against biopsy data from two patients., Findings: We demonstrate controlled, clinically unapparent, reversible and multimodally trackable brain white matter demyelination in a large animal model. De-/remyelination dynamics were slower than reported for rodent models and paralleled by a degree of secondary axonal pathology. Regression modelling of ultrastructural parameters (g-ratio, axon thickness) predicted EM features of cerebral de- and remyelination in human data., Interpretation: We validated our minipig model of demyelinating brain diseases by employing human diagnostic tools and comparing it with biopsy data from patients with cerebral demyelination., Funding: This work was supported by the DFG under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198) and TRR 274/1 2020, 408885537 (projects B03 and Z01)., Competing Interests: Declaration of interests CS, SH, BL, EL and TL are part of Ergosurg GmbH, which developed and manufactured the navigation system, the trackable instruments and the robotic system. VMB has received consulting fees from Brainlab. IY has received grants from the German Federal Ministry of Education and Research (BMBF) and the German Research Foundation (DFG), consulting fees from ABX-CRO, Blue Earth Diagnostics and Pentixapharm, honoraria from Piramal, support for attending meeting from the Society of Nuclear Medicine and Molecular Imaging, the European Association of Nuclear Medicine, the Slovenian Neuroscience Association (SiNAPSA) and the International Brain Research Organization, and is a member of the Neuroimaging Committee, European Association of Nuclear Medicine, the Board of Directors, Brain Imaging Council, Society of Nuclear Medicine and Molecular Imaging as well as the Molecular Connectivity Working Group. JK has received consulting fees from Novartis, possesses stock options at Bonescreen GmbH and was supported by the European Research Council, the DFG and the BMBF. TM has received speaker fees from Novartis and Roche as well as travel support from Novartis. BH has received consulting fees from GLG Consulting, Sandoz and Polpharma, possesses issued patents for detection of antibodies against KIR4.1 in a subpopulation of patients with multiple sclerosis, as well as genetic determinants of neutralizing antibodies to interferon, and has participated on Data Safety Monitoring and Advisory Boards for Novartis, Sandoz, Polpharma, Allergycare, TG Therapeutics and Biocon., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2024
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49. Quantitative susceptibility mapping in multiple sclerosis: A systematic review and meta-analysis.

Author

Voon CC, Wiltgen T, Wiestler B, Schlaeger S, and Mühlau M

Subjects
Humans, Gray Matter diagnostic imaging, Gray Matter pathology, Brain diagnostic imaging, Brain pathology, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis pathology, Magnetic Resonance Imaging methods
Abstract

Background: Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising non-invasive tool for multiple sclerosis (MS) in research and clinical practice., Objective: We performed a systematic review and meta-analysis on the use of QSM in MS., Methods: Our review was prospectively registered on PROSPERO (CRD42022309563). We searched five databases for studies published between inception and 30th April 2023. We identified 83 English peer-reviewed studies that applied QSM images on MS cohorts. Fifty-five included studies had at least one of the following outcome measures: deep grey matter QSM values in MS, either compared to healthy controls (HC) (k = 13) or correlated with the score on the Expanded Disability Status Scale (EDSS) (k = 7), QSM lesion characteristics (k = 22) and their clinical correlates (k = 17), longitudinal correlates (k = 11), histological correlates (k = 7), or correlates with other imaging techniques (k = 12). Two meta-analyses on deep grey matter (DGM) susceptibility data were performed, while the remaining findings could only be analyzed descriptively., Results: After outlier removal, meta-analyses demonstrated a significant increase in the basal ganglia susceptibility (QSM values) in MS compared to HC, caudate (k = 9, standardized mean difference (SDM) = 0.54, 95 % CI = 0.39-0.70, I 2  = 46 %), putamen (k = 9, SDM = 0.38, 95 % CI = 0.19-0.57, I 2  = 59 %), and globus pallidus (k = 9, SDM = 0.48, 95 % CI = 0.28-0.67, I 2  = 60 %), whereas thalamic QSM values exhibited a significant reduction (k = 12, SDM = -0.39, 95 % CI = -0.66--0.12, I 2  = 84 %); these susceptibility differences in MS were independent of age. Further, putamen QSM values positively correlated with EDSS (k = 4, r = 0.36, 95 % CI = 0.16-0.53, I 2  = 0 %). Regarding rim lesions, four out of seven studies, representing 73 % of all patients, reported rim lesions to be associated with more severe disability. Moreover, lesion development from initial detection to the inactive stage is paralleled by increasing, plateauing (after about two years), and gradually decreasing QSM values, respectively. Only one longitudinal study provided clinical outcome measures and found no association. Histological data suggest iron content to be the primary source of QSM values in DGM and at the edges of rim lesions; further, when also considering data from myelin water imaging, the decrease of myelin is likely to drive the increase of QSM values within WM lesions., Conclusions: We could provide meta-analytic evidence for DGM susceptibility changes in MS compared to HC; basal ganglia susceptibility is increased and, in the putamen, associated with disability, while thalamic susceptibility is decreased. Beyond these findings, further investigations are necessary to establish the role of QSM in MS for research or even clinical routine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2024
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50. Cortical Thin Patch Fraction Reflects Disease Burden in MS: The Mosaic Approach.

Author

Tahedl M, Wiltgen T, Voon CC, Berthele A, Kirschke JS, Hemmer B, Mühlau M, Zimmer C, and Wiestler B

Subjects
Humans, Artificial Intelligence, Magnetic Resonance Imaging methods, Biomarkers, Atrophy pathology, Brain pathology, Disease Progression, Multiple Sclerosis pathology
Abstract

Background and Purpose: GM pathology plays an essential role in MS disability progression, emphasizing the importance of neuroradiologic biomarkers to capture the heterogeneity of cortical disease burden. This study aimed to assess the validity of a patch-wise, individual interpretation of cortical thickness data to identify GM pathology, the "mosaic approach," which was previously suggested as a biomarker for assessing and localizing atrophy., Materials and Methods: We investigated the mosaic approach in a cohort of 501 patients with MS with respect to 89 internal and 651 external controls. The resulting metric of the mosaic approach is the so-called thin patch fraction, which is an estimate of overall cortical disease burden per patient. We evaluated the mosaic approach with respect to the following: 1) discrimination between patients with MS and controls, 2) classification between different MS phenotypes, and 3) association with established biomarkers reflecting MS disease burden, using general linear modeling., Results: The thin patch fraction varied significantly between patients with MS and healthy controls and discriminated among MS phenotypes. Furthermore, the thin patch fraction was associated with disease burden, including the Expanded Disability Status Scale, cognitive and fatigue scores, and lesion volume., Conclusions: This study demonstrates the validity of the mosaic approach as a neuroradiologic biomarker in MS. The output of the mosaic approach, namely the thin patch fraction, is a candidate biomarker for assessing and localizing cortical GM pathology. The mosaic approach can furthermore enhance the development of a personalized cortical MS biomarker, given that the thin patch fraction provides a feature on which artificial intelligence methods can be trained. Most important, we showed the validity of the mosaic approach when referencing data with respect to external control MR imaging repositories., (© 2024 by American Journal of Neuroradiology.)

Published
2023
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