7 results
GP.2 Changes in Leptin, CCL16 and sTNF-RII as a distinctive plasma immune profile in patients with fast progressing ALS
- V Picher-Martel, H Boutej, P Cordeau, H Kaneb, J Julien, A Genge, N Dupré, J Kriz
-
- Journal:
- Canadian Journal of Neurological Sciences / Volume 48 / Issue s3 / November 2021
- Published online by Cambridge University Press:
- 05 January 2022, p. S12
-
- Article
-
- You have access Access
- Export citation
-
Background: Amyotrophic lateral sclerosis (ALS) is highly heterogeneous with survival rate ranging from months to decades. Approximately 10-20% of patients develop a rapidly progressive disease and may die within the first year. Therefore, there is an increasing need for an early detection of unique molecular signatures associated with more aggressive forms of disease as it may help identify therapeutic targets. Methods: To identify a unique molecular signature in fast progressing patients, we recruited 45 sporadic ALS (sALS) patients and 35 age-matched healthy controls and measured 62 immune markers in plasma using cytokines array. Results: We found that leptin was significantly downregulated in plasma of sALS patients and more importantly in fast progressing disease. Immune markers CCL16 and sTNF-RII were significantly increased in rapidly progressing disease. We also found that leptin was significantly downregulated in plasma of SOD1G93A mice across disease stage. This was caused by an increased in levels of phospho-AMPK in mice adipocytes and in adipocytes exposed to fast sALS patients’ plasma. Conclusions: We propose that the combination of decreased plasma leptin levels and up-regulation in CCL16/sTNF-RII may be used as a prognostic biomarker to identify fast progressing ALS patients. This unique immune/metabolic profile may cause dysfunction in metabolic homeostasis.
A.04 The classification of autosomal recessive cerebellar ataxias: a consensus statement from the society for research on the cerebellum and ataxias task force
- M Beaudin, A Matilla-Dueñas, B Soong, J Pedroso, OG Barsottini, H Mitoma, S Tsuji, JD Schmahmann, M Manto, GA Rouleau, CJ Klein, N Dupre
-
- Journal:
- Canadian Journal of Neurological Sciences / Volume 46 / Issue s1 / June 2019
- Published online by Cambridge University Press:
- 05 June 2019, p. S9
-
- Article
-
- You have access Access
- Export citation
-
Background: There is currently no accepted classification of recessive cerebellar ataxias, a group of disorders characterized by important genetic heterogeneity and complex phenotypes. The objective of this task force was to build a consensus and develop a clinical and pathophysiological classification for recessive ataxias. Methods: The work of this task force was based on a scoping systematic review of the literature that identified recessive disorders characterized primarily by a cerebellar motor syndrome and cerebellar degeneration. The task force regrouped 12 international ataxia experts who decided on general orientation and specific issues. Results: We identified 59 disorders that are classified as primary recessive ataxias. For each of these disorders, we present geographical and ethnical specificities along with distinctive clinical and imagery features. The primary recessive ataxias were organized in a clinical and a pathophysiological classification, and we present a general clinical approach to the patient presenting with ataxia. We also identified a list of 48 complex multisystem disorders in which ataxia is a secondary feature. Conclusions: This classification is based on a scoping systematic review of the literature and results from a sconsensus among a panel of international experts. It promotes a unified understanding of recessive cerebellar disorders for clinicians and researchers.
14. Pre-symptomatic detection of cytoplasmic TDP-43 accumulation using tissue-engineered skin model derived from C9ORF72-FALS patients
- B. Paré, L. Touzel-Deschênes, R. Lamontagne, M-S. Lamarre, F-D. Scott, C. Gaudet, H.T. Khuong, P. Dion, S. Saikali, J-P. Bouchard, P.V. Gould, G. Rouleau, N. Dupré, F. Berthod, F. Gros-Louis
-
- Journal:
- Canadian Journal of Neurological Sciences / Volume 42 / Issue S2 / August 2015
- Published online by Cambridge University Press:
- 06 August 2015, p. S6
-
- Article
-
- You have access Access
- Export citation
-
Amyotrophic lateral sclerosis (ALS) is an adult-onset disease characterized by the selective degeneration of motor neurons in the brain and spinal cord resulting in progressive paralysis and death. Current diagnosis of ALS is based on clinical assessment of related symptoms, which appear only late in the disease course after degeneration of a significant number of motor neurons. As a result, the identification and development of disease-modifying therapies is difficult, making ALS an incurable disease. Novel strategies for early diagnosis of ALS, to monitor disease progression and to assess response to existing and future treatments are urgently needed.
Many neurological disorders, including ALS, are accompanied by skin changes that often precede the onset of neurological symptoms. We have developed a unique ALS tissue-engineered skin model (ALS-TES), derived from the cells of ALS patients, in order to study the earliest stages of ALS-related skin pathology. For each participant, two skin biopsies were collected using a 6-mm diameter punch biopsy. Tissue-engineered skin was then generated from isolated keratinocytes and fibroblasts, and examined by routine histochemistry and immunohistochemistry, as well as by confocal microscopy. The ALS-TES model presents a number of striking features including altered epidermal differentiation, abnormal dermo-epidermal junction, delamination, keratinocyte infiltration, collagen disorganization and cytoplasmic TDP-43 inclusions, which are not seen in skin models derived from healthy subjects. The same abnormal skin model changes were detected skin models derived from the cells of pre- symptomatic C9orf72-linked ALS patients carrying the GGGGCC DNA repeat expansion. Consequently, our ALS-TES skin model could represent a renewable source of human tissue to better understand the physiopathological mechanisms underlying this disease, including cytoplasmic TDP43 accumulation, and lead to better tools for early diagnosis and disease monitoring.
Contributors
-
- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
-
- Book:
- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
- Print publication:
- 27 April 2015, pp ix-xxx
-
- Chapter
- Export citation
A Novel Mutation in a Large French-Canadian Family with LGMD1B
- Nicolas Chrestian, Paul N. Valdmanis, Najmeddine Echahidi, Denis Brunet, Jean-Pierre Bouchard, Peter Gould, Guy A. Rouleau, Jean Champagne, Nicolas Dupré
-
- Journal:
- Canadian Journal of Neurological Sciences / Volume 35 / Issue 3 / July 2008
- Published online by Cambridge University Press:
- 02 December 2014, pp. 331-334
-
- Article
-
- You have access Access
- Export citation
-
Background:
Limb girdle muscular dystrophy type 1B is an autosomal dominant disease characterized by late onset proximal muscle involvement associated with cardiac complications such as atrioventricular conduction blocks, dilated cardiomyopathy, and sudden death.
Objective:Define the full phenotypic spectrum of a new mutation in the LMNA gene causing limb girdle muscular dystrophy type 1B.
Methods:We identified a large French Canadian family with the LGMD 1B phenotype and a cardiac conduction disease phenotype that carried a new mutation in the LMNA gene and sought to define its full phenotypic spectrum by performing complete neurological and cardiac evaluations, muscle biopsy, RNA and DNA studies.
Results:The proband and 12 living at risk relatives were tested. In total, we identified seven carriers of a new (IVS9-3C>G) LMNA gene mutation. Of the three symptomatic patients, all had cardiac involvement, but only two presented proximal limb weakness. The one available muscle biopsy demonstrated a normally expressed lamin A/C protein, localized at the nuclear envelope. RNA study revealed a loss of exon 10 transcription caused by the IVS9-3C to G splicing mutation.
Conclusions:We have identified a new mutations in the LMNA gene in a French-Canadian family. This diagnosis has important implications for affected patients and their siblings since they may eventually require pacemaker implantation.
Establishing a Canadian Registry of Patients with Amyotrophic Lateral Sclerosis
- L. Korngut, A. Genge, M. Johnston, T. Benstead, P. Bourque, H. Briemberg, A. Casey, M. D'Amour, N. Dupré, D. Figlewicz, W. Hader, W. Johnston, S. Kalra, M. Melanson, C. O'Connell, G. Rouleau, C. Shoesmith, J. Wee, L. Zinman
-
- Journal:
- Canadian Journal of Neurological Sciences / Volume 40 / Issue 1 / January 2013
- Published online by Cambridge University Press:
- 23 September 2014, pp. 29-35
-
- Article
-
- You have access Access
- Export citation
-
Background:
Amyotrophic lateral sclerosis (ALS) is a devastating cause of progressive weakness, respiratory failure and death. To date there is no effective therapy to meaningfully extend survival but continuously emerging targets and putative treatments are studied in clinical trials. Canadian epidemiological data on ALS is scarce and the socioeconomic impact of ALS on Canadian society is unclear. The Canadian Neuromuscular Disease Registry (CNDR) is a national clinic-based registry of patients with neuromuscular diseases with the goal of facilitating the design and execution of clinical research.
Methods:We conducted a national stakeholder survey to assess interest for a Canadian ALS registry and an assessment of expected case ascertainment. A dataset derivation meeting was held to establish the registry medical dataset.
Results:We report the results of the national stakeholder survey, case ascertainment assessment, and the derived dataset that have resulted in the current implementation of a Canadian registry of patients with ALS.
Conclusions:The development of this long sought-after resource is a significant step forward for the Canadian ALS patient and research communities that will result in more efficient clinical trial recruitment and advancements in our understanding of ALS in Canada.
Diversity of ARSACS Mutations in French-Canadians
- I. Thiffault, M.J. Dicaire, M. Tetreault, K.N. Huang, J. Demers-Lamarche, G. Bernard, A. Duquette, R. Larivière, K. Gehring, A. Montpetit, P.S. McPherson, A. Richter, L. Montermini, J. Mercier, G.A. Mitchell, N. Dupré, C. Prévost, J.P. Bouchard, J. Mathieu, B. Brais
-
- Journal:
- Canadian Journal of Neurological Sciences / Volume 40 / Issue 1 / January 2013
- Published online by Cambridge University Press:
- 23 September 2014, pp. 61-66
-
- Article
-
- You have access Access
- Export citation
-
Background:
The growing number of spastic ataxia of Charlevoix-Saguenay (SACS) gene mutations reported worldwide has broadened the clinical phenotype of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The identification of Quebec ARSACS cases without two known SACS mutation led to the development of a multi-modal genomic strategy to uncover mutations in this large gene and explore phenotype variability.
Methods:Search for SACS mutations by combining various methods on 20 cases with a classical French-Canadian ARSACS phenotype without two mutations and a group of 104 sporadic or recessive spastic ataxia cases of unknown cause. Western blot on lymphoblast protein from cases with different genotypes was probed to establish if they still expressed sacsin.
Results:A total of 12 mutations, including 7 novels, were uncovered in Quebec ARSACS cases. The screening of 104 spastic ataxia cases of unknown cause for 98 SACS mutations did not uncover carriers of two mutations. Compounds heterozygotes for one missense SACS mutation were found to minimally express sacsin.
Conclusions:The large number of SACS mutations present even in Quebec suggests that the size of the gene alone may explain the great genotypic diversity. This study does not support an expanding ARSACS phenotype in the French-Canadian population. Most mutations lead to loss of function, though phenotypic variability in other populations may reflect partial loss of function with preservation of some sacsin expression. Our results also highlight the challenge of SACS mutation screening and the necessity to develop new generation sequencing methods to ensure low cost complete gene sequencing.