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5. Neocortical β‐amyloid area is associated with dementia and APOE in the oldest‐old

Author

Berlau, Daniel J, Corrada, María M, Robinson, John L, Geser, Felix, Arnold, Steven E, Lee, Virginia M‐Y, Kawas, Claudia H, and Trojanowski, John Q

Subjects
Neurosciences, Brain Disorders, Aging, Neurodegenerative, Dementia, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, 2.1 Biological and endogenous factors, Aetiology, Neurological, Aged, 80 and over, Amyloid beta-Peptides, Apolipoprotein E2, Apolipoprotein E4, Female, Genotype, Geriatric Assessment, Humans, Male, Mental Status Schedule, Neocortex, Neurofibrillary Tangles, Plaque, Amyloid, Alzheimer, Apolipoprotein E, Beta-amyloid, Oldest-old, Clinical Sciences, Geriatrics
Abstract

ObjectiveApolipoprotein E (APOE) ε2 carriers may be protected from dementia because of reduced levels of cortical β-amyloid. In the oldest-old, however, APOE ε2 carriers have high β-amyloid plaque scores and preserved cognition. We compared different measures of β-amyloid pathology across APOE genotypes in the oldest-old, and their relationship with dementia.MethodsThe study included 96 participants from The 90+ Study. Using all information, dementia diagnoses were made. Neuropathological examination included staging for amyloid plaques and β-amyloid cortical percent area stained by NAB228 antibody.ResultsBoth APOE ε2 and APOE ε4 carriers had high Consortium to Establish a Registry for Alzheimer's Disease plaque scores. However, APOE ε2 carriers had low cortical β-amyloid percent areas. β-amyloid percent area was associated with dementia across APOE genotypes.ConclusionsLower levels of percent area in APOE ε2 carriers may reflect lower total β-amyloid and may contribute to APOE ε2 carriers' decreased risk of dementia, despite high β-amyloid plaque scores. The relationship between β-amyloid plaques and dementia in the oldest-old may vary by APOE genotype.

Published
2013

6. Neocortical and hippocampal amyloid-β and tau measures associate with dementia in the oldest-old

Author

Robinson, John L, Geser, Felix, Corrada, Maria M, Berlau, Daniel J, Arnold, Steven E, Lee, Virginia M-Y, Kawas, Claudia H, and Trojanowski, John Q

Subjects
Health Services and Systems, Health Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Neurosciences, Brain Disorders, Neurodegenerative, Dementia, Acquired Cognitive Impairment, Alzheimer's Disease, 2.1 Biological and endogenous factors, Aetiology, Neurological, Aged, 80 and over, Amyloid beta-Peptides, Female, Hippocampus, Humans, Longitudinal Studies, Male, Neocortex, Neurofibrillary Tangles, Plaque, Amyloid, tau Proteins, Alzheimer's, tau, amyloid, dementia, oldest-old, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

The emergence of longevity in the modern world has brought a sense of urgency to understanding age-related neurodegenerative diseases such as Alzheimer's disease. Unfortunately, there is a lack of consensus regarding the correlation between the pathological substrates of neurodegeneration and dementia status, particularly in the oldest-old. To better understand the pathological correlates of dementia in the oldest-old, we characterized the topographical spread and severity of amyloid-β, tau, TDP-43 and α-synuclein pathologies in the 90+ Study, a prospective longitudinal population-based study of ageing and dementia. Neuropathological analysis with immunohistochemically labelled sections was carried out blind to clinical diagnosis on the first 108 participants of the 90+ Study who came to autopsy including participants with dementia (n = 66) and without dementia (n = 42). We used quantitative and/or semi-quantitative measures to assess the burden of amyloid-β, tau, TDP-43 and α-synuclein pathologies as well as hippocampal sclerosis. Amyloid-β and tau were the predominant pathologies in the 90+ Study cohort and both amyloid-β area and tau area occupied measures were strongly associated with the presence of dementia, as was Braak staging but semi-quantitative plaque scores were not. Notably, TDP-43 pathology also correlated with dementia, while α-synuclein distribution did not. In addition, hippocampal sclerosis was specific to participants with dementia and correlated with the presence of limbic TDP-43. In contrast to previous reports, we found that tau and amyloid-β continue to be robust pathological correlates of dementia, even in the oldest-old. While individuals with no dementia had limited hippocampal tau and neocortical amyloid-β pathology, dementia associated with an expansion in pathology, including increased neocortical tau and hippocampal amyloid-β plaques, more abundant neocortical amyloid-β deposition and hippocampal sclerosis with its attendant TDP-43 pathology.

Published
2011

7. FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration.

Author

Urwin, Hazel, Josephs, Keith A, Rohrer, Jonathan D, Mackenzie, Ian R, Neumann, Manuela, Authier, Astrid, Seelaar, Harro, Van Swieten, John C, Brown, Jeremy M, Johannsen, Peter, Nielsen, Jorgen E, Holm, Ida E, FReJA Consortium, Dickson, Dennis W, Rademakers, Rosa, Graff-Radford, Neill R, Parisi, Joseph E, Petersen, Ronald C, Hatanpaa, Kimmo J, White, Charles L, Weiner, Myron F, Geser, Felix, Van Deerlin, Vivianna M, Trojanowski, John Q, Miller, Bruce L, Seeley, William W, van der Zee, Julie, Kumar-Singh, Samir, Engelborghs, Sebastiaan, De Deyn, Peter P, Van Broeckhoven, Christine, Bigio, Eileen H, Deng, Han-Xiang, Halliday, Glenda M, Kril, Jillian J, Munoz, David G, Mann, David M, Pickering-Brown, Stuart M, Doodeman, Valerie, Adamson, Gary, Ghazi-Noori, Shabnam, Fisher, Elizabeth MC, Holton, Janice L, Revesz, Tamas, Rossor, Martin N, Collinge, John, Mead, Simon, and Isaacs, Adrian M

Subjects
FReJA Consortium, Hippocampus, Frontal Lobe, Humans, Dyskinesias, RNA-Binding Protein FUS, tau Proteins, DNA-Binding Proteins, Prevalence, Sequence Analysis, DNA, Mental Disorders, Age of Onset, Mutation, Adult, Middle Aged, Female, Male, Frontotemporal Lobar Degeneration, Sequence Analysis, DNA, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Through an international consortium, we have collected 37 tau- and TAR DNA-binding protein 43 (TDP-43)-negative frontotemporal lobar degeneration (FTLD) cases, and present here the first comprehensive analysis of these cases in terms of neuropathology, genetics, demographics and clinical data. 92% (34/37) had fused in sarcoma (FUS) protein pathology, indicating that FTLD-FUS is an important FTLD subtype. This FTLD-FUS collection specifically focussed on aFTLD-U cases, one of three recently defined subtypes of FTLD-FUS. The aFTLD-U subtype of FTLD-FUS is characterised clinically by behavioural variant frontotemporal dementia (bvFTD) and has a particularly young age of onset with a mean of 41 years. Further, this subtype had a high prevalence of psychotic symptoms (36% of cases) and low prevalence of motor symptoms (3% of cases). We did not find FUS mutations in any aFTLD-U case. To date, the only subtype of cases reported to have ubiquitin-positive but tau-, TDP-43- and FUS-negative pathology, termed FTLD-UPS, is the result of charged multivesicular body protein 2B gene (CHMP2B) mutation. We identified three FTLD-UPS cases, which are negative for CHMP2B mutation, suggesting that the full complement of FTLD pathologies is yet to be elucidated.

Published
2010

10. The natural history of multiple system atrophy: a prospective European cohort study

Author

Wenning, Gregor K, Geser, Felix, Krismer, Florian, Seppi, Klaus, Duerr, Susanne, Boesch, Sylvia, Köllensperger, Martin, Goebel, Georg, Pfeiffer, Karl P, Barone, Paolo, Pellecchia, Maria Teresa, Quinn, Niall P, Koukouni, Vasiliki, Fowler, Clare J, Schrag, Anette, Mathias, Christopher J, Giladi, Nir, Gurevich, Tanya, Dupont, Erik, Ostergaard, Karen, Nilsson, Christer F, Widner, Håkan, Oertel, Wolfgang, Eggert, Karla Maria, Albanese, Alberto, del Sorbo, Francesca, Tolosa, Eduardo, Cardozo, Adriana, Deuschl, Günther, Hellriegel, Helge, Klockgether, Thomas, Dodel, Richard, Sampaio, Cristina, Coelho, Miguel, Djaldetti, Ruth, Melamed, Eldad, Gasser, Thomas, Kamm, Christoph, Meco, Giuseppe, Colosimo, Carlo, Rascol, Olivier, Meissner, Wassilios G, Tison, François, and Poewe, Werner

Published
2013
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21. CONTRIBUTING AUTHORS

Author

Bhatia, Kailash, primary, Bonifati, Vincenzo, additional, James Brooks, David, additional, Brotchie, Jonathan M., additional, John Burn, David, additional, Compta, Yaroslau, additional, Dawson, Ted M., additional, Deuschl, Gunther, additional, Dickson, Dennis W., additional, Fahn, Stanley, additional, Farrer, Matthew James, additional, Fasano, Alfonso, additional, Ferraris, Alessandro, additional, Fox, Susan, additional, Gaig, Carles, additional, Gasser, Thomas, additional, Geser, Felix, additional, Gupta, Amitabh, additional, Halliday, Glenda, additional, Hamani, Clement, additional, Hatano, Taku, additional, Hattori, Nobutaka, additional, Hening, Wayne, additional, Jankovic, Joseph, additional, Jellinger, Kurt, additional, Josephs, Keith A., additional, Klein, Christine, additional, Köllensperger, Martin, additional, Kubo, Shin-ichiro, additional, Landwehrmeyer, G.B., additional, Lang, Anthony E.T., additional, Laxton, Adrian W., additional, Lozano, Andres M., additional, Ludolph, Albert C., additional, Machida, Yutaka, additional, Moro, Elena, additional, Morris, Huw R., additional, Murphy, Karen, additional, Obeso, José A., additional, Warren Olanow, C., additional, Poewe, Werner, additional, Rademakers, Rosa, additional, Santamaria, Joan, additional, Sato, Shigeto, additional, Schapira, Anthony H.V., additional, Schneider, Susanne A., additional, Seppi, Klaus, additional, Shoulson, Ira, additional, Singer, Harvey S., additional, Stefanova, Nadia, additional, Tanner, Caroline M., additional, Thomas, Madhavi, additional, Thompson, Philip, additional, Tolosa, Eduardo, additional, Trenkwalder, Claudia, additional, Valente, Enza Maria, additional, Vidailhet, Marie, additional, Walker, Ruth H., additional, Warner, Thomas T., additional, Weintraub, Daniel, additional, Wenning, Gregor K., additional, Weydt, Patrick, additional, Wider, Christian W., additional, and Wszolek, Zbigniew K., additional

Published
2010
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24. Contributors

Author

Aguzzi, Adriano, primary, Albers, James W., additional, Alger, Jeffry R., additional, Allen, Richard P., additional, Aranow, Cynthia, additional, Backonja, Misha-Miroslav, additional, Balmer, Curtis W., additional, Batchelor, Tracy, additional, Benarroch, Eduardo E., additional, Berciano, José, additional, Bertram, Edward H., additional, Bhatia, Radhika, additional, Biller, Jose, additional, Birbeck, Gretchen L., additional, Bleck, Thomas P., additional, Bosworth, Brian P., additional, Bowsher, David, additional, Brooks, Benjamin, additional, Bukelis, Irena, additional, Caronna, John J., additional, Carter, John C., additional, Cavaletti, Guido, additional, Chand, Pratap, additional, Chong, Ji Y., additional, Cleland, James C., additional, Colosimo, Carlo, additional, Condon, Timothy P., additional, Sander Connolly, E., additional, Cortopassi, Gino, additional, Crystal, Ronald G., additional, Cutting, Laurie E., additional, Dafer, Rima M., additional, Dalakas, Marinos C., additional, Dalmau, Josep, additional, de Saint Martin, Anne, additional, Detre, John A., additional, Dhawan, Vijay, additional, Diamond, Betty, additional, Patrick Andrews Drummond, Sean, additional, Eidelberg, David, additional, Eisenach, John H., additional, Elshihabi, Said, additional, Fan, QiWen, additional, Fealey, Robert D., additional, Ferrari, Michel D., additional, Ferriero, Donna M., additional, Fink, Gereon R., additional, Fischbeck, Kenneth H., additional, Furie, Karen, additional, Gálvez-Jiménez, Néstor, additional, Geser, Felix, additional, Glatzel, Markus, additional, Goadsby, Peter J., additional, Goldin, Alan L., additional, Greenland, Karen J., additional, Griggs, Robert C., additional, Gutmann, David H., additional, Hagel, Christian, additional, Hagerman, Paul J., additional, Harris, Kendra, additional, Hartung, Hans-Peter, additional, Hemmer, Bernhard, additional, Heppner, Frank L., additional, Herbert, Martha R., additional, Herrmann, David N., additional, Hirano, Michio, additional, Hirsch, Edouard, additional, Hoff, Julian T., additional, Hoon, Alexander H., additional, Hyman, Bradley T., additional, Jain, Samay, additional, Jänig, Wilfrid, additional, Jaradeh, Safwan S., additional, Jellinger, Kurt A., additional, Joyner, Michael J., additional, Kaufmann, Walter E., additional, Keep, Richard F., additional, Kellogg, Aaron, additional, Kieseier, Bernd C., additional, Kinsman, Stephen L., additional, Köller, Hubertus, additional, Kowal, Czeslawa, additional, Lamszus, Katrin, additional, Landzberg, Brian R., additional, Lev, Michael H., additional, Lieberman, David N., additional, Lim, Leland E., additional, Lipkin, Paul H., additional, Litvan, Irene, additional, London, Zachary, additional, Low, Phillip A., additional, Mackay, Meggan, additional, Mahowald, Mark W., additional, Manzo, Luigi, additional, Maragakis, Nicholas J., additional, Masdeu, Joseph C., additional, Mazzoni, Pietro, additional, McLean, Pamela J., additional, Mercadante, Sebastiano, additional, Meyer, Ana-Claire, additional, Mignot, Emmanuel, additional, Miller, Steven P., additional, Mostofsky, Stewart, additional, Mrugala, Maciej, additional, Newcomer, Anne, additional, Nobbio, Lucilla, additional, Noorbakhsh, Farshid, additional, Novak, Peter, additional, O'Donoghue, John L., additional, Orr, Harry T., additional, Fleming Outiero, Tiago, additional, Palestrant, David, additional, Pedley, Timothy A., additional, Perez-Velasquez, Jose-Luis, additional, Perlis, Michael L., additional, Persson, Anders I., additional, Phillips, Joanna J., additional, Piersall, Linda, additional, Pigeon, Wilfred R., additional, Pomerantz, Stuart R., additional, Pop-Busui, Rodica, additional, Power, Christopher, additional, Powers, James M., additional, Rando, Thomas A., additional, Ratan, Rajiv R., additional, Rimrodt, Sheryl L., additional, Rothstein, Jeffrey D., additional, Russell, James W., additional, Rutka, James T., additional, Saling, Michael M., additional, Scharfman, Helen E., additional, Schenck, Carlos H., additional, Schenone, Angelo, additional, Schrage, William G., additional, Schroeter, Michael, additional, Schütz, Peter W., additional, Simmons, Zachary, additional, Singer, Harvey S., additional, Singh, Ajay K., additional, Singleton, J.R., additional, Smith, A.G., additional, Carter Snead, O., additional, Sorenson, Eric J., additional, Srikanth, Velandai, additional, Stöckler, Sylvia, additional, Sumner, Charlotte J., additional, Swash, Michael, additional, Teener, James W., additional, Thornton, Charles A., additional, Thrift, Amanda G., additional, Töpfnerz, Nicole, additional, Tsuji, Shoji, additional, Turetz, Meredith L., additional, Twydell, Paul, additional, Vercueil, Laurent, additional, Vernino, Steven, additional, Vincent, Angela, additional, Volpe, Bruce T., additional, Wagner, Kenneth R., additional, Walkley, Steven U., additional, Weil, Robert J., additional, Weiss, William A., additional, Weksler, Babette B., additional, Wenning, Gregor K., additional, Westner, Ingo M., additional, Westphal, Manfred, additional, Wilkinson, Philip A., additional, Wong, Alice, additional, Xi, Guohua, additional, Zajac, Jeffrey D., additional, and Zeitzer, Jamie M., additional

Published
2007
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25. Multiple System Atrophy

Author

Colosimo, Carlo, primary, Geser, Felix, additional, Benarroch, Eduardo E., additional, and Wenning, Gregor K., additional

Published
2007
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28. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS

Author

Elden, Andrew C., Kim, Hyung-Jun, Hart, Michael P., Chen-Plotkin, Alice S., Johnson, Brian S., Fang, Xiaodong, Armakola, Maria, Geser, Felix, Greene, Robert, Lu, Min Min, Padmanabhan, Arun, Clay-Falcone, Dana, McCluskey, Leo, Elman, Lauren, Juhr, Denise, Gruber, Peter J., Rüb, Udo, Auburger, Georg, Trojanowski, John Q., Lee, Virginia M.-Y., Van Deerlin, Vivianna M., Bonini, Nancy M., and Gitler, Aaron D.

Published
2010
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30. Minocycline 1-year therapy in multiple-system-atrophy: Effect on clinical symptoms and [11C] (R)-PK11195 PET (MEMSA-trial)

Author

Dodel, Richard, Spottke, Annika, Gerhard, Alexander, Reuss, Alexander, Reinecker, Sylvia, Schimke, Nicole, Trenkwalder, Claudia, Sixel-Döring, Friederike, Herting, Birgit, Kamm, Christoph, Gasser, Thomas, Sawires, Martin, Geser, Felix, Köllensperger, Martin, Seppi, Klaus, Kloss, Manja, Krause, Martin, Daniels, Christine, Deuschl, Günther, Böttger, Silke, Naumann, Markus, Lipp, Axel, Gruber, Doreen, Kupsch, Andreas, Du, Yansheng, Turkheimer, Federico, Brooks, David J., Klockgether, Thomas, Poewe, Werner, Wenning, Gregor, Schade-Brittinger, Carmen, Oertel, Wolfgang H., and Eggert, Karla

Published
2010
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33. List of Contributors

Author

Ashizawa, Tetsuo, primary, Baier, P.C., additional, Becker, Lore, additional, Bennett, David J., additional, Berke, Brett, additional, Betarbet, Ranjita, additional, Bhatia, Kailash P., additional, Bibbiani, Francesco, additional, Blake, David T., additional, Borchelt, David R., additional, Bose, Prodip, additional, Bragg, D. Cristopher, additional, Brashear, Allison, additional, Breakefield, Xandra O., additional, Bressman, Susan, additional, Burke, Kathleen, additional, Byl, Nancy N., additional, Caldwell, Guy A., additional, Caldwell, Kim A., additional, Cao, Songsong, additional, Cenci, M. Angela, additional, Chesselet, Marie-Françoise, additional, Colosimo, Carlo, additional, Dang, Mai, additional, Dennis, Julie A., additional, Devys, Didier, additional, Dietrich, Paula, additional, Dragatsis, Ioannis, additional, D'Souza, Ian, additional, Elble, Rodger J., additional, Evinger, Craig, additional, Fernagut, Pierre-Olivier, additional, Fernandez, Hubert H., additional, Fink, John K., additional, Fleming, Sheila M., additional, Fletcher, Colin F., additional, Fox, Lyle, additional, Fowler, Stephen C., additional, Friedman, Joseph H., additional, Geser, Felix, additional, Ghorayeb, Imad, additional, Gorassini, Monica, additional, Greenamyre, J. Timothy, additional, Harvey, Philip J., additional, Heales, Simon J.R., additional, Healy, Peter J., additional, Helmlinger, Dominique, additional, Hess, Ellen J., additional, Hillman, Ralph, additional, Homanics, Gregg E., additional, Hyland, Keith, additional, Izevbaye, Iyare, additional, Jackson-Lewis, Vernice, additional, Jinnah, H.A., additional, Jurkowski, Anita J., additional, Kassem, Iris S., additional, Kaytor, Michael D., additional, Kralic, Jason E., additional, LeDoux, Mark, additional, Lewis, Jada, additional, Li, Yuqing, additional, Lieberman, David, additional, Linn, Gary S., additional, Litvan, Irene, additional, Lombroso, Paul J., additional, Louis, Elan D., additional, Lundblad, Martin, additional, Marsh, J. Lawrence, additional, McGowan, Eileen, additional, McKerchar, T.L., additional, Merzenich, Michael, additional, Morrow, A. Leslie, additional, Naquet, Robert, additional, Nass, Richard, additional, Navas, Parvoneh Poorkaj, additional, O'Buckley, Todd K., additional, Oh, Justin D., additional, Ohye, Chihiro, additional, Orr, Harry T., additional, Osterman, Jessica L., additional, Pallanck, Leo J., additional, Pandolfo, Massimo, additional, Pendleton, Robert G., additional, Peng, Haixiang, additional, Peng, I-Feng, additional, Perez, Dianne M., additional, Perlman, Susan L., additional, Perlmutter, Joel S., additional, Petravicz, Jeremy, additional, Pfeiffer, Ronald F., additional, Phillips, James O., additional, Pranzatelli, Michael R., additional, Pulst, Stefan-M., additional, Rainier, Shirley, additional, Rao, Jayaraman, additional, Richter, Angelika, additional, Robinson, Farrel R., additional, Ross, Christopher A., additional, Sachdev, Perminder S., additional, Saunders-Pullman, Rachel, additional, Schellenberg, Gerard D., additional, Schilling, Gabriele, additional, Schofield, Peter R., additional, Sharma, Nutan, additional, Sherer, Todd B., additional, Silva-Barrat, Carmen, additional, Singer, Harvey S., additional, Smeyne, Richard Jay, additional, Smith-Hicks, Constance, additional, Stacy, Mark, additional, Stafanova, Nadia, additional, Standaert, David G., additional, Subramony, S.H., additional, Tabbal, Samer D., additional, Tai, Kwok-Keung, additional, Thompson, Floyd J., additional, Thompson, Leslie M., additional, Tison, François, additional, Trenkwalder, Claudia, additional, Truong, Daniel D., additional, Ueda, Atsushi, additional, Vartiainen, Suvi, additional, Weiher, Hans, additional, Weiss, Avery H., additional, Wenning, Gregor Karl, additional, Whitworth, Alexander J., additional, Windsor, Peter A., additional, Wong, Garry, additional, Wu, Chun-Fang, additional, and Zarcone, T.J., additional

Published
2005
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35. Clinical and Pathological Continuum of Multisystem TDP-43 Proteinopathies

Author

Geser, Felix, Martinez-Lage, Maria, Robinson, John, Uryu, Kunihiro, Neumann, Manuela, Brandmeir, Nicholas J., Xie, Sharon X., Kwong, Linda K., Elman, Lauren, McCluskey, Leo, Clark, Chris M., Malunda, Joe, Miller, Bruce L., Zimmerman, Earl A., Qian, Jiang, Van Deerlin, Vivianna, Grossman, Murray, Lee, Virginia M.-Y., and Trojanowski, John Q.

Published
2009

36. Red flags for multiple system atrophy

Author

Köllensperger, Martin, Geser, Felix, Seppi, Klaus, Stampfer-Kountchev, Michaela, Sawires, Martin, Scherfler, Christoph, Boesch, Sylvia, Mueller, Joerg, Koukouni, Vasiliki, Quinn, Niall, Pellecchia, Maria Teresa, Barone, Paolo, Schimke, Nicole, Dodel, Richard, Oertel, Wolfgang, Dupont, Erik, stergaard, Karen, Daniels, Christine, Deuschl, Günther, Gurevich, Tanya, Giladi, Nir, Coelho, Miguel, Sampaio, Cristina, Nilsson, Christer, Widner, Håkan, Sorbo, Francesca Del, Albanese, Alberto, Cardozo, Adriana, Tolosa, Eduardo, Abele, Michael, Klockgether, Thomas, Kamm, Christoph, Gasser, Thomas, Djaldetti, Ruth, Colosimo, Carlo, Meco, Giuseppe, Schrag, Anette, Poewe, Werner, and Wenning, Gregor K.

Published
2008
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40. Health-Related Quality of Life in Multiple System Atrophy

Author

Schrag, Anette, Geser, Felix, Stampfer-Kountchev, Michaela, Seppi, Klaus, Sawires, Martin, Köllensperger, Martin, Scherfler, Christoph, Quinn, Niall, Pellecchia, Maria T., Barone, Paolo, del Sorbo, Francesca, Albanese, Alberto, Ostergaard, Karen, Dupont, Erik, Cardozo, Adriana, Tolosa, Eduardo, Nilsson, Christer F., Widner, Håkan, Lindvall, Olle, Giladi, Nir, Gurevich, Tanya, Daniels, Christine, Deuschl, Günther, Coelho, Miguel, Sampaio, Cristina, Abele, Michael, Klockgether, Thomas, Schimke, Nicole, Eggert, Karla M., Oertel, Wolfgang, Djaldetti, Ruth, Colosimo, Carlo, Meco, Giuseppe, Poewe, Werner, and Wenning, Gregor K.

Published
2006
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42. Progression of multiple system atrophy (MSA): A prospective natural history study by the European MSA Study Group (EMSA SG)

Author

Geser, Felix, Wenning, Gregor K., Seppi, Klaus, Stampfer-Kountchev, Michaela, Scherfler, Christoph, Sawires, Martin, Frick, Carolin, Ndayisaba, Jean-Pierre, Ulmer, Hanno, Pellecchia, Maria T., Barone, Paolo, Kim, Hee T., Hooker, Juzar, Quinn, Niall P., Cardozo, Adriana, Tolosa, Eduardo, Abele, Michael, Klockgether, Thomas, stergaard, Karen, Dupont, Erik, Schimke, Nicole, Eggert, Karla M., Oertel, Wolfgang, Djaldetti, Ruth, and Poewe, Werner

Published
2006
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47. Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS)

Author

Wenning, Gregor K., Tison, François, Seppi, Klaus, Sampiao, Cristina, Diem, Anja, Yekhlef, Farid, Ghorayeb, Imad, Ory, Fabienne, Galitzky, Monique, Scaravilli, Tommaso, Bozi, Maria, Colosimo, Carlo, Gilman, Sid, Shults, Clifford W., Quinn, Niall P., Rascol, Olivier, Poewe, Werner, Dupont, Erik, Ostergaard, Karen, Tolosa, Eduardo, Klockgether, Thomas, Dodel, Richard, Abele, Michael, Pollak, Pierre, Geser, Felix, Stamfer, Michaela, Deuschl, Günther, Daniels, Christine, Coelho, Miguel, Pirtosek, Zvezdan, Brooks, David J., Fowler, Claire, Lees, Andrew, Mathias, Christopher J., Revesz, Tamas, Gerhard, Alexander, Holton, Janice, Schrag, Anette, Wood, Nick, Lindvall, Olle, Widner, Håkan, Grabowski, Martin, Nilsson, Christer F., Oertel, Wolfgang, Eggert, Karla Maria, Schimke, Nicole, Albanese, Alberto, del Sorbo, Francesco, Barone, Paolo, Carella, Francesco, Djaljetti, Ruth, Meco, Giuseppe, Berciano, Jose, Gonzalez-Mandly, Andres, Giladi, Nir, Gurevich, Tanya, Gasser, Thomas, Kamm, Christoph, Aquilonius, Sten Magnus, and Bergquist, Jonas

Subjects
Male, Gerontology, medicine.medical_specialty, Cerebellar Ataxia, Scale (ratio), education, Autonomic Nervous System, Severity of Illness Index, Speech Disorders, Part iii, Disability Evaluation, Hypotension, Orthostatic, Atrophy, Physical medicine and rehabilitation, Erectile Dysfunction, Parkinsonian Disorders, Rating scale, Surveys and Questionnaires, Internal consistency, Activities of Daily Living, Validation, medicine, Humans, Interrater Reliability, Age of Onset, Observer Variation, Reproducibility of Results, Multiple System Atrophy, Urinary Retention, Unified Multiple System Atrophy Rating Scale, medicine.disease, Degree (music), Inter-rater reliability, Urinary Incontinence, Neurology, Female, International Cooperative Ataxia Rating Scale, Neurology (clinical), Psychology
Abstract

We aimed to develop and validate a novel rating scale for multiple system atrophy (Unified Multiple System Atrophy Rating Scale - UMSARS). The scale comprises the following components: Part I, historical, 12 items; Part II, motor examination, 14 items; Part III, autonomic examination; and Part IV, global disability scale. For validation purposes, 40 MSA patients were assessed in four centers by 4 raters per center (2 senior and 2 junior raters). The raters applied the UMSARS, as well as a range of other scales, including the Unified Parkinson's Disease Rating Scale (UPDRS) and the International Cooperative Ataxia Rating Scale (ICARS). Internal consistency was high for both UMSARS-1 (Crohnbach's alpha = 0.84) and UMSARS-II (Crohnbach's alpha = 0.90) sections. The interrater reliability of most of the UMSARS-I and -II items as well as of total UMSARS-I and -II subscores was substantial (k (w) = 0.6-0.8) to excellent (k (w) > 0.8). UMSARS-II correlated well with UPDRS-III and ICARS (rs > 0.8). Depending on the degree of the patient's disability, completion of the entire UMSARS took 30 to 45 minutes. Based on our findings, the UMSARS appears to be a multidimensional, reliable, and valid scale for semiquantitative clinical assessments of MSA patients.

Published
2004

48. Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11)C] (R)-PK11195 PET (MEMSA-trial)

Author

Dodel, Richard, Spottke, Annika, Gerhard, Alexander, Reuss, Alexander, Reinecker, Sylvia, Schimke, Nicole, Trenkwalder, Claudia, Sixel-Döring, Friederike, Herting, Birgit, Kamm, Christoph, Gasser, Thomas, Sawires, Martin, Geser, Felix, Köllensperger, Martin, Seppi, Klaus, Kloss, Manja, Krause, Martin, Daniels, Christine, Deuschl, Günther, Böttger, Silke, Naumann, Markus, Lipp, Axel, Gruber, Doreen, Kupsch, Andreas, Du, Yansheng, Turkheimer, Federico, Brooks, David J., Klockgether, Thomas, Poewe, Werner, Wenning, Gregor, Schade-Brittinger, Carmen, Oertel, Wolfgang H., and Eggert, Karla

Subjects
Adult, Male, Time Factors, Minocycline, Middle Aged, Multiple System Atrophy, Isoquinolines, Magnetic Resonance Imaging, Severity of Illness Index, Statistics, Nonparametric, Neuroprotective Agents, Treatment Outcome, Double-Blind Method, Positron-Emission Tomography, Quality of Life, Humans, Female, Aged, Follow-Up Studies
Abstract

The aim of the study was to investigate the efficacy of the antibiotic minocycline as a drug treatment in patients with Multiple-System-Atrophy Parkinson-type (MSA-P). Sixty-three patients were randomized to minocycline 200 mg/d (n = 32) or a matching placebo (n = 31). The primary outcome variable was the change in the value of the motor score of the Unified Multiple-System-Atrophy Rating-Scale (UMSARSII) from baseline to 48 weeks. Secondary outcome variables included subscores and individual Parkinsonian symptoms as determined by the UMSARS and the Unified-Parkinson's-Disease Rating-Scale (UPDRS). Health-related quality of life (HrQoL) was assessed using the EQ-5D and SF-12. "Progression rate" was assumed to be reflected in the change in motor function over 48 weeks. At 24 weeks and 48 weeks of follow-up, there was a significant deterioration in motor scores in both groups, but neither the change in UMSARSII nor in UPDRSIII differed significantly between treatment groups, i.e. "progression rate" was considered to be similar in both treatment arms. HrQoL did not differ among the two treatment arms. In a small subgroup of patients (n = 8; minocycline = 3, placebo = 5)[(11)C](R)-PK11195-PET was performed. The three patients in the minocycline group had an attenuated mean increase in microglial activation as compared to the placebo group (P = 0.07) and in two of them individually showed decreased [11C](R)-PK11195 binding actually decreased. These preliminary PET-data suggest that minocycline may interfere with microglial activation. The relevance of this observation requires further investigation. This prospective, 48 week, randomized, double-blind, multinational study failed to show a clinical effect of minocycline on symptom severity as assessed by clinical motor function.

Published
2009

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