49 results on '"Matthew Brodsky"'
Search Results
2. Hoehn and Yahr Stage and Striatal Dat-SPECT Uptake Are Predictors of Parkinson’s Disease Motor Progression
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Holly Jackson, Judith Anzures-Cabrera, Kirsten I. Taylor, Gennaro Pagano, PASADENA Investigators, Prasinezumab Study Group, Claudia Altendorf, Chareyna Anandan, Giulia Andrews, Solène Ansquer, Raphaele Arrouasse, Sana Aslam, Jean-Philippe Azulay, Jeanette Baker, Ernest Balaguer Martinez, Shadi Barbu, Kara Bardram, Danny Bega, Helena Bejr-Kasem Marco, Isabelle Benatru, Eve Benchetrit, Felix Bernhard, Amir Besharat, Sagari Bette, Amelie Bichon, Andrew Billnitzer, Sophie Blondeau, Thomas Boraud, Freiderike Borngräber, James Boyd, Kathrin Brockmann, Matthew Brodsky, Ethan Brown, Christof Bruecke, Fabienne Calvas, Monica Canelo, Federico Carbone, Claire Carroll, Laura Casado Fernandez, Catherine Cassé-Perrot, Anna Castrioto, Helene Catala, Justine Chan, Samia Cheriet, Anthony Ciabarra, Joseph Classen, Juliana Coleman, Robert Coleman, Yaroslau Compta, Anne-Gaëlle Corbillé, Jean-Christophe Corvol, Mariana Cosgaya, Nabila Dahodwala, Philippe Damier, Elodie David, Thomas Davis, Marissa Dean, Berengere Debilly, Janell DeGiorgio, Andres Deik, Laure Delaby, Marie-Helene Delfini, Pascal Derkinderen, Philipp Derost, Maria de Toledo, Lisa Deuel, Ann Marie Diaz-Hernandez, Cameron Dietiker, Karina Dimenshteyn, Julio Dotor, Franck Durif, Jens Ebentheuer, Karla Maria Eggert, Sara Eichau Madueño, Claudia Eickhoff, Aaron Ellenbogen, Philipp Ellmerer, Ines Esparragosa Vazquez, Alexandre Eusebio, Siobhan Ewert, John Fang, Danielle Feigenbaum, Frederique Fluchere, Alexandra Foubert-Samier, Marie Fournier, Anne Fradet, Valerie Fraix, Samuel Frank, Franca Fries, Monique Galitzky, Marisol Gallardó Pérez, Jose Manuel García Moreno, Carmen Gasca, Thomas Gasser, Joyce Gibbons, Caroline Giordana, Alicia Gonzalez Martinez, Ira Goodman, Arantza Gorospe, Marie Goubeaud, David Grabli, Mangone Graziella, Stephan Grimaldi, Jeffrey Gross, Raquel Guimaraes-Costa, Andreas Hartmann, Christian Hartmann, Travis Hassell, Robert Hauser, Antonio Hernandez, Jorge Hernandez-Vara, Guenter Hoeglinger, Christian Homedes, Andrea Horta-Barba, Jean-Luc Houeto, Julius Huebl, Jennifer Hui, Stuart Isaacson, Joseph Jankovic, Annette Janzen, Junior Jauregui, Jocelyne Jiao, Maria Jose Marti Domenech, Xavier Joseph, Srinath Kadimi, Pat Kaminski, Silja Kannenberg, Jan Kassubek, Maya Katz, Kevin Klos, Shannon Klos, Christopher Kobet, Jennifer Koebert, Patricia Krause, Andrea Kuehn, Jaime Kulisevsky Bojarsky, Rajeev Kumar, Martin Kunz, Lille Kurvits, Kimberly Kwei, Simon Laganiere, Brice Laurens, Johannes Levin, Oren Levy, Peter LeWitt, Gurutz Linazasoro Cristóbal, Irene Litvan, Karlo Lizarraga, Katherine Longardner, Rocio Lopez, Lydia Lopez Manzanares, Sara Lucas del Pozo, Maria Rosario Luquin Puido, Nijee Luthra, Kelly Lyons, Sylvia Maass, Gerrit Machetanz, Yolanda Macias, David Maltete, Jorge Uriel Manez Miro, Louise-Laure Mariani, Juan Marin, Kathrin Marini, Ana Marques, Gloria Marti, Saul Martinez, Wassilios Meissner, Sara Meoni, Brit Mollenhauer, Dunia Mon Martinez, Johnson Moon, Elena Moro, Peter Morrison, Christoph Muehlberg, Manpreet Multani, Christine Murphy, Anthony Nicholas, Rajesh Pahwa, Antonio Palasi, Heidi Pape, Neepa Patel, Prity Patel, Marina Peball, Elizabeth Peckham, Terry Peery, Rafael Perez, Jesus Perez, Alisa Petit, Elmar Pinkhardt, Werner Poewe, Elsa Pomies, Cecile Preterre, Joseph Quinn, Olivier Rascol, Philippe Remy, Irene Richard, Benjamin Roeben, Emily Ruether, Jost-Julian Rumpf, David Russell, Hayet Salhi, Daniela Samaniego-Toro, Alexandra Samier-Foubert, Antonio Sanchez, Emmanuelle Schmitt, Alfons Schnitzler, Oliver Schorr, Julie Schwartzbard, Kerstin Schweyer, Klaus Seppi, Victoria Sergo, Holly Shill, Andrew Siderowf, Tanya Simuni, Umberto Spampinato, Ashok Sriram, Natividad Stover, Caroline Tanner, Arjun Tarakad, Carolyn Taylor, Claire Thalamus, Thomas Toothaker, Nadege Van Blercom, Nora Vanegas-Arrogave, Lydia Vela, Sylvian Vergnet, Tiphaine Vidal, Jonathan Vöglein, Ryan Walsh, Cheryl Waters, Mirko Wegscheider, Endy Weidinger, Caroline Weill, Gregor Wenzel, Tatiana Witjas, Isabel Wurster, Brenton Wright, Milan Zimmermann, Rafael Zuzuarregui, Markus Abt, Atieh Bamdadian, Teresa Barata, Nicholas Barbet, Sara Belli, Frank Boess, Azad Bonni, Edilio Borroni, Anne Boulay, Markus Britschgi, Jerome Chague, Valerie Cosson, Christian Czech, Dennis Deptula, Cheikh Diack, Rachelle Doody, Juergen Dukart, Giulia D’Urso, Sebastian Dziadek, Hannah Eddleston, Chris Edgar, Laurent Essioux, Morgan Farell, Rebecca Finch, Paulo Fontoura, Waltraud Gruenbauer, Andrea Hahn, Stefan Holiga, Michael Honer, Shirin Jadidi, Kelly Johnson-Wood, Markus Keller, Timothy Kilchenmann, Martin Koller, Thomas Kremer, Thomas Kustermann, Claire Landsdall, Michael Lindemann, Florian Lipsmeier, Cecile Luzy, Marianne Manchester, Maddalena Marchesi, Ferenc Martenyi, Meret Martin-Facklam, Katerina Mironova, Annabelle Monnet, Emma Moore, Daniel K Ness, Markus Niggli, Tania Nikolcheva, Susanne Ostrowitzki GP, Benedicte Passmard, Agnes Poirier, Anke Post, Megana Prasad, Nathalie Pross, Tiffany Quock, Benedicte Ricci, Ellen Rose, Christoph Sarry, Christine Schubert, Dennis Selkoe, Jeff Sevigny, Kaycee Sink, Hannah Staunton, Tim Steven, Alexander Strasak, Hanno Svoboda KT, Radhika Tripuraneni, Dylan Trundell, Daniel Umbricht, Lynne Verselis, Annamarie Vogt, Ekaterina Volkova-Volkmar, Cornelia Weber, Silke Weber, and Wagner Zago
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PASADENA ,PPMI (Parkinson’s Progression Markers Initiative) ,Parkinson’s disease ,progression predictors ,ridge regression ,disease stage ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Currently, no treatments available for Parkinson’s disease (PD) can slow PD progression. At the early stage of the disease, only a subset of individuals with PD progress quickly, while the majority have a slowly progressive form of the disease. In developing treatments that aim to slow PD progression, clinical trials aim to include individuals who are likely to progress faster, such that a treatment effect, if one exists, can be identified easier and earlier. The aim of the present study was to identify baseline predictors of clinical progression in early PD. We analyzed 12-month data acquired from the PASADENA trial Part 1 (NCT03100149, n = 76 participants who were allocated to the placebo arm and did not start symptomatic therapy) and the Parkinson’s Progression Markers Initiative (PPMI) study (n = 139 demographically and clinically matched participants). By using ridge regression models including clinical characteristics, imaging, and non-imaging biomarkers, we found that Hoehn and Yahr stage and dopamine transporter single-photon emission computed tomography specific binding ratios (Dat-SPECT SBR) in putamen ipsilateral to the side of motor symptom onset predicted PD progression at the early stage of the disease. Further studies are needed to confirm the validity of these predictors to identify with high accuracy individuals with early PD with a faster progression phenotype.
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- 2021
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3. A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA): Rationale, Design, and Baseline Data
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Gennaro Pagano, Frank G. Boess, Kirsten I. Taylor, Benedicte Ricci, Brit Mollenhauer, Werner Poewe, Anne Boulay, Judith Anzures-Cabrera, Annamarie Vogt, Maddalena Marchesi, Anke Post, Tania Nikolcheva, Gene G. Kinney, Wagner M. Zago, Daniel K. Ness, Hanno Svoboda, Markus Britschgi, Susanne Ostrowitzki, Tanya Simuni, Kenneth Marek, Martin Koller, Jeff Sevigny, Rachelle Doody, Paulo Fontoura, Daniel Umbricht, Azad Bonni, PASADENA Investigators, Prasinezumab Study Group, Claudia Altendorf, Chareyna Anandan, Giulia Andrews, Solène Ansquer, Raphaele Arrouasse, Sana Aslam, Jean-Philippe Azulay, Jeanette Baker, Ernest Balaguer Martinez, Shadi Barbu, Kara Bardram, Danny Bega, Helena Bejr-Kasem Marco, Isabelle Benatru, Eve Benchetrit, Felix Bernhard, Amir Besharat, Sagari Bette, Amelie Bichon, Andrew Billnitzer, Sophie Blondeau, Thomas Boraud, Freiderike Borngräber, James Boyd, Kathrin Brockmann, Matthew Brodsky, Ethan Brown, Christof Bruecke, Fabienne Calvas, Monica Canelo, Federico Carbone, Claire Carroll, Laura Casado Fernandez, Catherine Cassé-Perrot, Anna Castrioto, Helene Catala, Justine Chan, Samia Cheriet, Anthony Ciabarra, Joseph Classen, Juliana Coleman, Robert Coleman, Yaroslau Compta, Anne-Gaëlle Corbillé, Jean-Christophe Corvol, Mariana Cosgaya, Nabila Dahodwala, Philippe Damier, Elodie David, Thomas Davis, Marissa Dean, Berengere Debilly, Janell DeGiorgio, Andres Deik, Laure Delaby, Marie-Helene Delfini, Pascal Derkinderen, Philipp Derost, Maria de Toledo, Lisa Deuel, Ann Marie Diaz-Hernandez, Cameron Dietiker, Karina Dimenshteyn, Julio Dotor, Franck Durif, Jens Ebentheuer, Karla Maria Eggert, Sara Eichau Madueño, Claudia Eickhoff, Aaron Ellenbogen, Philipp Ellmerer, Ines Esparragosa Vazquez, Alexandre Eusebio, Siobhan Ewert, John Fang, Danielle Feigenbaum, Frederique Fluchere, Alexandra Foubert-Samier, Marie Fournier, Anne Fradet, Valerie Fraix, Samuel Frank, Franca Fries, Monique Galitzky, Marisol Gallardó Pérez, Jose Manuel García Moreno, Carmen Gasca, Thomas Gasser, Joyce Gibbons, Caroline Giordana, Alicia Gonzalez Martinez, Ira Goodman, Arantza Gorospe, Marie Goubeaud, David Grabli, Mangone Graziella, Stephan Grimaldi, Jeffrey Gross, Raquel Guimaraes-Costa, Andreas Hartmann, Christian Hartmann, Travis Hassell, Robert Hauser, Antonio Hernandez, Jorge Hernandez-Vara, Günter Höglinger, Christian Homedes, Andrea Horta-Barba, Jean-Luc Houeto, Julius Huebl, Jennifer Hui, Stuart Isaacson, Joseph Jankovic, Annette Janzen, Junior Jauregui, Jocelyne Jiao, Maria Jose Marti Domenech, Xavier Joseph, Srinath Kadimi, Pat Kaminski, Silja Kannenberg, Jan Kassubek, Maya Katz, Kevin Klos, Shannon Klos, Christopher Kobet, Jennifer Koebert, Patricia Krause, Andrea Kuehn, Jaime Kulisevsky Bojarsky, Rajeev Kumar, Martin Kunz, Lille Kurvits, Kimberly Kwei, Simon Laganiere, Brice Laurens, Johannes Levin, Oren Levy, Peter LeWitt, Gurutz Linazasoro Cristóbal, Irene Litvan, Karlo Lizarraga, Katherine Longardner, Rocio Lopez, Lydia Lopez Manzanares, Sara Lucas del Pozo, Maria Rosario Luquin Puido, Nijee Luthra, Kelly Lyons, Sylvia Maass, Gerrit Machetanz, Yolanda Macias, David Maltete, Jorge Uriel Manez Miro, Louise-Laure Mariani, Juan Marin, Kathrin Marini, Ana Marques, Gloria Marti, Saul Martinez, Wassilios Meissner, Sara Meoni, Dunia Mon Martinez, Johnson Moon, Elena Moro, Peter Morrison, Christoph Muehlberg, Manpreet Multani, Christine Murphy, Anthony Nicholas, Rajesh Pahwa, Antonio Palasi, Heidi Pape, Neepa Patel, Prity Patel, Marina Peball, Elizabeth Peckham, Terry Peery, Rafael Perez, Jesus Perez, Alisa Petit, Elmar Pinkhardt, Elsa Pomies, Cecile Preterre, Joseph Quinn, Olivier Rascol, Philippe Remy, Irene Richard, Benjamin Roeben, Emily Ruether, Jost-Julian Rumpf, David Russell, Hayet Salhi, Daniela Samaniego-Toro, Alexandra Samier-Foubert, Antonio Sanchez, Emmanuelle Schmitt, Alfons Schnitzler, Oliver Schorr, Julie Schwartzbard, Kerstin Schweyer, Klaus Seppi, Victoria Sergo, Holly Shill, Andrew Siderowf, Umberto Spampinato, Ashok Sriram, Natividad Stover, Caroline Tanner, Arjun Tarakad, Carolyn Taylor, Claire Thalamus, Thomas Toothaker, Nadege Van Blercom, Nora Vanegas-Arrogave, Lydia Vela, Sylvian Vergnet, Tiphaine Vidal, Jonathan Vöglein, Ryan Walsh, Cheryl Waters, Mirko Wegscheider, Endy Weidinger, Caroline Weill, Gregor Wenzel, Tatiana Witjas, Isabel Wurster, Brenton Wright, Milan Zimmermann, Rafael Zuzuarregui, Markus Abt, Atieh Bamdadian, Teresa Barata, Nicholas Barbet, Sara Belli, Frank Boess, Edilio Borroni, Jerome Chague, Valerie Cosson, Christian Czech, Dennis Deptula, Cheikh Diack, Juergen Dukart, Giulia D'Urso, Sebastian Dziadek, Hannah Eddleston, Chris Edgar, Laurent Essioux, Morgan Farell, Rebecca Finch, Waltraud Gruenbauer, Andrea Hahn, Stefan Holiga, Michael Honer, Shirin Jadidi, Kelly Johnson-Wood, Markus Keller, Timothy Kilchenmann, Thomas Kremer, Thomas Kustermann, Claire Landsdall, Michael Lindemann, Florian Lipsmeier, Cecile Luzy, Marianne Manchester, Ferenc Martenyi, Meret Martin-Facklam, Katerina Mironova, Annabelle Monnet, Emma Moore, Daniel K Ness, Markus Niggli, Benedicte Passmard, Agnes Poirier, Megana Prasad, Nathalie Pross, Tiffany Quock, Ellen Rose, Christoph Sarry, Christine Schubert, Dennis Selkoe, Kaycee Sink, Hannah Staunton, Tim Steven, Alexander Strasak, Kirsten Taylor, Radhika Tripuraneni, Dylan Trundell, Lynne Verselis, Ekaterina Volkova-Volkmar, Cornelia Weber, Silke Weber, and Wagner Zago
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Parkinson's disease ,alpha-synuclein (α-syn) ,prasinezumab ,monoclonal antibodies ,disease progression ,MDS-UPDRS = Movement Disorder Society—Unified Parkinson's Disease Rating Scale ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease.Objective: The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD.Methods: The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1,500 or 4,500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40–80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g., resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson's Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations.Results: Of the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. Mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society—Unified Parkinson's Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS sum of Parts I + II + III [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) showed a similar severity in MDS-UPDRS scores (e.g., MDS-UPDRS sum of Parts I + II + III [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve).Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD.Trial Registration: NCT03100149.
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- 2021
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4. RiboTag is a flexible tool for measuring the translational state of targeted cells in heterogeneous cell cultures
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Adam J. Lesiak, Matthew Brodsky, and John F. Neumaier
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cell-type specific gene expression ,translational profiling ,RiboTag ,TRAP. primary neuronal cultures ,Biology (General) ,QH301-705.5 - Abstract
Primary neuronal cultures are a useful tool for measuring pharmacological- and transgene-regulated gene expression; however, accurate measurements can be confounded by heterogeneous cell types and inconsistent transfection efficiency. Here we describe our adaptation of a ribosomal capture strategy that was designed to be used in transgenic mice expressing tagged ribosomal subunits (RiboTag) in specific cell types, thereby allowing measurement of translating RNAs from desired cell types within complex tissues. Using this strategy we were able to isolate and analyze neuron-specific RNA despite the presence of glia by co-transfecting experimental plasmids with plasmids that selectively express RiboTag in neurons. RiboTag immunoprecipitation was capable of recovering high integrity RNA from small numbers of transfected cells that can then be interrogated by a variety of methods (e.g., RT-qPCR, PCR array, RNA-Seq) and compared with basal RNA expression of the entire culture. Additionally, we demonstrate how co-transfection of RiboTag with small hairpin RNA (shRNA) constructs can validate and accurately assess the degree of gene expression knockdown, and how RiboTag can be used to measure receptor-mediated gene regulation with transiently expressed designer receptors exclusively activated by designer drugs (DREADDs). RiboTag co-transfection represents a convenient and powerful tool to isolate RNA from a specific subset of cultured cells with a variety of applications for experiments in vitro.
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- 2015
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5. Predictors of multi-domain cognitive decline following DBS for treatment of Parkinson's disease
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Johannes C. Rothlind, Michele K. York, Ping Luo, Kim Carlson, William J. Marks, Frances M. Weaver, Matthew Stern, Kenneth A. Follett, John E. Duda, Domenic J. Reda, Kenneth Follett, Frances Weaver, Dolores Ippolito, Gatana Stoner, Tammy Barnett, Ken Bukowski, Rosemarie DeNicolo, Kwan Hur, Joyce Jimenez, Jan Motyka, Domenic Reda, Theresa Simon, Bharat Thakkar, Robert Woolson, Carol Fye, William Gagne, Crystal Harris, Jill Heemskerk, Claudia Moy, Paul Sheehy, Timothy O'Leary, Grant D. Huang, Louis Fiore, Robert Hall, Kevin Stroupe, Kim Burchiel, William Koller, Rajesh Pahwa, Johannes Rothlind, Oren Sagher, Roy Bakay, Rick Chappell, Robert Hart, Robert Holloway, George McCabe, Margaret Schenkman, Jamal Taha, Julia Buckelew, Marilyn Garin, Sharon Matzek, Donna Smith, Jeff Bronstein, John Duda, Penelope Hogarth, Kathryn Holloway, Stacy Horn, Eugene C. Lai, Ali Samii, null Farah Atassi, Cecilia Bello, Lisette Bunting-Perry, Tina Conn, Alice Cugley, Nanette Eubank, Linda Fincher, Romay Franks, Tammy Harris, Mariann Haselman, Susan Heath, Miriam Hirsch, Virginia Janovsky, Elaine Lanier, Mary Lloyd, Susan Loehner, Susan O'Connor, Ligaya Ordonez, Heather Maccarone, Kelli Massey-Makhoul, Mary Matthews, Elizabeth Meyn, Keiko Mimura, Wes Morrow, Tammy Searles, Jamye Valotta, Usha Vasthare, Monica Volz, Constance Ward, Rebecca Warker, Heidi Watson, Pamela Willson, Mark Baron, Matthew Brodsky, Vincent Calabrese, Gordon Campbell, Amy Colcher, Emad Farag, Eva Henry, Jyh-Gong Hou, Gail Kang, Galit Kleiner-Fisman, Jeff Kraakevik, John Nutt, Jill Ostrem, Aliya Sarwar, Indu Subramanian, Zeba Vanek, Gordon Baltuch, Antonio De Salles, Jorge Eller, Paul Larson, Richard Simpson, Philip Starr, William Carne, Tom Erikson, Jeffrey Kreutzer, Mario Mendez, Paul Moberg, John Ragland, Ronald Seel, Daniel Storzbach, Alexander Troster, Michele York, and Jurg Jaggi
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Neurology ,Subthalamic Nucleus ,Deep Brain Stimulation ,Humans ,Cognitive Dysfunction ,Parkinson Disease ,Neurology (clinical) ,Neuropsychological Tests ,Geriatrics and Gerontology ,Aged - Abstract
Statistically and clinically significant cognitive declines are observed in a small subset of individuals with Parkinson's Disease (PD) following treatment with Deep Brain Stimulation (DBS).We examine the association between multi-domain cognitive decline (MCD) and demographic and baseline clinical variables and the incidence of serious adverse events (SAE) arising within a six-month interval following DBS for PD.Study participants with PD who displayed MCD at 6-month follow-up evaluation after DBS (n = 18) were contrasted with individuals with PD from the same study who did not show cognitive decline after DBS (n = 146). Logistic regression analyses were employed to assess relationship between predictors, including age (70 years old), pre-DBS cognitive screening test performance, SAE, and MCD. MCD+ and MCD-groups were also compared on other baseline clinical and demographic variables.MCD showed modest association with older age and lower baseline neurocognitive screening performance, whereas the groups did not differ on most other baseline clinical and demographic variables. SAEs during the study interval were the most robust predictor of MCD in the DBS group. A variety of SAEs were documented in study participants experiencing MCD after DBS surgery, including, but not limited to, infections and small intracranial hemorrhages.Older age and lower baseline cognition measured prior to treatment are associated with MCD measured at six-months after DBS. SAE occurring following DBS surgery are also predictive of MCD. These predictors may reflect aspects of "frailty" in advanced PD. Risk factors for SAE warrant careful consideration in clinical trials.
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- 2022
6. Effect of Urate-Elevating Inosine on Early Parkinson Disease Progression: The SURE-PD3 Randomized Clinical Trial
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Tanya Simuni, Holly A. Shill, Matthew Brodsky, Marcie Rabin, Michael A. Schwarzschild, Kenneth Marek, Cheryl Waters, Cindy Casaceli, Steven A. Gunzler, Stephen G. Reich, Codrin Lungu, Sarah Elizabeth Zauber, Kellie Keith, Shyamal H. Mehta, Dariush Mozaffarian, Valerie Suski, Marie Saint-Hilaire, John L. Goudreau, Alice Rudolph, Ruth B. Schneider, Aaron Daley, Eric A. Macklin, Zoltan Mari, Grace F. Crotty, Andres Deik, Alberto J. Espay, Ashley Laroche, Sherri Mosovsky, Joohi Jimenez-Shahed, Mark S. LeDoux, Cynthia Poon, Ashley Gerald, John C. Morgan, Carolyn Peterson, Joseph H. Friedman, David Klements, Robert A. Hauser, Doozie Russell, David Simon, Kathrin LaFaver, Vanessa K. Hinson, Richard B. Dewey, Melissa Ainslie, Jason Aldred, Tiago A. Mestre, John Y. Fang, Liana S. Rosenthal, Grace Bwala, Raymond C. James, Binit B. Shah, Gearoid M. McMahon, Ariane Park, Rajeev Kumar, Lin Zhang, Ivan Bodis-Wollner, Mya C. Schiess, Katherine F. Callahan, David Oakes, Kelvin L. Chou, Melissa Kostrzebski, Roger Kurlan, Lisa Gauger, Albert Y. Hung, Melissa Bixby, Ira Shoulson, Michael Soileau, James T. Boyd, Peter A LeWitt, Burton L. Scott, Claire Henchcliffe, Patricia Kaminski, Alberto Ascherio, Cornelia Kamp, Lindsay Pothier, Anwar Ahmed, Jill Ciccarello, David J. Houghton, April Langhammer, Rebecca Fitzgerald, Maureen A. Leehey, Anthony E. Lang, Carmen Serrano, Martha McGraw, David Shprecher, Jennifer Durphy, Aleksandar Videnovic, Danish Bhatti, Christine Hunter, Amber Servi Ratel, J. Antonelle de Marcaida, Christopher G. Goetz, Emily Houston, Rajesh Pahwa, Chadwick W. Christine, Gary C. Curhan, Irene Litvan, Christopher A. Beck, Leslie J. Cloud, Patrick Bolger, Karen Thomas, Natividad Stover, Karen Blindauer, Sushrut S. Waikar, and Susan R. Criswell
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medicine.medical_specialty ,business.industry ,Dopaminergic ,Unified Parkinson's disease rating scale ,General Medicine ,Placebo ,law.invention ,Clinical trial ,Randomized controlled trial ,law ,Internal medicine ,Severity of illness ,medicine ,Inosine ,business ,Adverse effect ,medicine.drug ,Original Investigation - Abstract
IMPORTANCE: Urate elevation, despite associations with crystallopathic, cardiovascular, and metabolic disorders, has been pursued as a potential disease-modifying strategy for Parkinson disease (PD) based on convergent biological, epidemiological, and clinical data. OBJECTIVE: To determine whether sustained urate-elevating treatment with the urate precursor inosine slows early PD progression. DESIGN, PARTICIPANTS, AND SETTING: Randomized, double-blind, placebo-controlled, phase 3 trial of oral inosine treatment in early PD. A total of 587 individuals consented, and 298 with PD not yet requiring dopaminergic medication, striatal dopamine transporter deficiency, and serum urate below the population median concentration (
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- 2021
7. Injections of IncobotulinumtoxinA at Intervals Less Than 10 weeks Are Effective and Safe for Cervical Dystonia Patients With Inadequate Benefit From Standard Injection Intervals
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Cynthia Comella, Robert Hauser, Stuart Isaacson, Daniel Truong, Odinachi Oguh, Jennifer Hui, Eric S. Molho, Matthew Brodsky, Erin Furr-Stimming, Georg Comes, Michael Hast, and David Charles
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Toxicology - Published
- 2022
8. Treatment of Cervical Dystonia Using Shorter IncobotulinumtoxinA Injection Intervals Improves Patient-Reported Outcomes in Those With Inadequate Benefits From Standard Intervals
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Stuart Isaacson, David Charles, Cynthia Comella, Daniel Truong, Odinachi Oguh, Jennifer Hui, Eric S. Molho, Matthew Brodsky, Erin Furr-Stimming, Georg Comes, Michael Hast, and Robert Hauser
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Toxicology - Published
- 2022
9. Alternating Thalamic Deep Brain Stimulation for Essential Tremor: A Trial to Reduce Habituation
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Amie L. Hiller, Charles F. Murchison, Matthew Brodsky, Shannon Anderson, Mara D Seier, and Joseph F. Quinn
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0301 basic medicine ,medicine.medical_specialty ,Activities of daily living ,Deep brain stimulation ,Essential tremor ,business.industry ,medicine.medical_treatment ,Thalamus ,Stimulation ,medicine.disease ,nervous system diseases ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Physical medicine and rehabilitation ,Neurology ,Initial visit ,medicine ,Neurology (clinical) ,Habituation ,business ,Research Articles ,030217 neurology & neurosurgery ,Treatment Arm - Abstract
Background DBS in the ventral intermediate nucleus (VIM) of the thalamus has been a revolutionary treatment for patients with essential tremor (ET) by reducing tremor. Unfortunately, some patients develop habituation to DBS and thus experience reduced efficacy and loss of tremor control. There are no standardized methods of addressing habituation to DBS. We propose alternating stimulation patterns as a way to reduce habituation. Methods This was a randomized, placebo-controlled trial for patients with VIM DBS for ET. Patients were randomized to either experimental treatment arm of alternating stimulation patterns on a weekly basis or standard care arm of continuous stimulation settings for 12 weeks. Primary outcome was change in the performance subscale of The Essential Tremor Rating Assessment Scale (TETRAS), which was performed at initial visit and 12-week follow-up. Secondary outcome included change in the activities of daily living subscale of TETRAS. Results Twenty-two patients were enrolled in the trial, and 16 were analyzed at follow-up. Experimental treatment subjects displayed sustained tremor control compared to standard care, as measured by the change in TETRAS performance subscale (-0.6 vs. 6.7 point change, respectively) with a 7.3 difference between the arms (P = 0.006). Conclusion Alternating stimulation patterns on a weekly basis for ET patients with VIM DBS reduced habituation in this pilot study. This study suggests that exposure to different stimulation groups may maintain better tremor control compared to constant stimulation parameters.
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- 2018
10. Restoration of Physiological Expression of 5-HT6 Receptor into the Primary Cilia of Null Mutant Neurons Lengthens Both Primary Cilia and Dendrites
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Atom J. Lesiak, Matthew Brodsky, John F. Neumaier, Alexandra G. Croicu, and N. Cohenca
- Subjects
0301 basic medicine ,Cell signaling ,Cell ,Biology ,Cell Line ,Mice ,03 medical and health sciences ,FYN ,Organelle ,Cyclic AMP ,medicine ,Animals ,Cilia ,Receptor ,Mice, Knockout ,Neurons ,Pharmacology ,Cilium ,Articles ,Dendrites ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Receptors, Serotonin ,5-HT6 receptor ,Molecular Medicine ,Serotonin ,Protein Binding ,Signal Transduction - Abstract
5-HT(6) (serotonin) receptors are promising targets for a variety of neuropsychiatric disorders and have been linked to several cellular signaling cascades. Endogenous 5-HT(6) receptors are restricted to the primary neuronal cilium, a small sensory organelle stemming from the cell body that receives numerous extrasynaptic signals. Inhibition of 5-HT(6) receptors decreases cilia length in primary neuronal cultures, but the signaling mechanisms involved are still unclear. Intense overexpression of exogenous 5-HT(6) receptors increases the probability for receptors to localize outside the primary cilium and have been associated with changes in cilia morphology and dendritic outgrowth. In the present study, we explore the role of 5-HT(6)R rescue on neuronal morphology in primary neuronal cultures from 5-HT(6)R-KO mice, at the same time maintaining a more physiologic level of expression, wherein the receptor localizes to cilia in 80%–90% of neurons (similar to endogenous 5-HT(6)R localization). We found that rescue of 5-HT(6)R expression is sufficient to increase cilia length and dendritic outgrowth, but primarily in neurons in which the receptor is located exclusively in the primary cilia. Additionally, we found that expression of 5-HT(6)R mutants deficient in agonist-stimulated cAMP or without the predicted Fyn kinase binding domain maintained constitutive activity for stimulating cAMP and still increased the length of cilia, and that the proposed Fyn kinase domain was required for stimulating dendritic outgrowth. These findings highlight the complexity of 5-HT(6)R function and localization, particularly with the use of exogenous overexpression, and provide greater understanding and potential mechanisms for 5-HT(6)R drug therapies.
- Published
- 2018
11. Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease
- Author
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Charles Murchison, Kim J. Burchiel, Mara Seier, Matthew Brodsky, Aaron Vederman, Jennifer Wilhelm, and Shannon Anderson
- Subjects
Male ,Deep brain stimulation ,Deep Brain Stimulation ,medicine.medical_treatment ,Motor Activity ,Globus Pallidus ,Severity of Illness Index ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Quality of life ,Subthalamic Nucleus ,Rating scale ,Surveys and Questionnaires ,Severity of illness ,medicine ,Humans ,Speech ,Wakefulness ,Intraoperative imaging ,Aged ,business.industry ,Imaging guidance ,Parkinson Disease ,Middle Aged ,nervous system diseases ,Treatment Outcome ,Dyskinesia ,Anesthesia ,Quality of Life ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Objective:To compare motor and nonmotor outcomes at 6 months of asleep deep brain stimulation (DBS) for Parkinson disease (PD) using intraoperative imaging guidance to confirm electrode placement vs awake DBS using microelectrode recording to confirm electrode placement.Methods:DBS candidates with PD referred to Oregon Health & Science University underwent asleep DBS with imaging guidance. Six-month outcomes were compared to those of patients who previously underwent awake DBS by the same surgeon and center. Assessments included an “off”-levodopa Unified Parkinson’s Disease Rating Scale (UPDRS) II and III, the 39-item Parkinson's Disease Questionnaire, motor diaries, and speech fluency.Results:Thirty participants underwent asleep DBS and 39 underwent awake DBS. No difference was observed in improvement of UPDRS III (+14.8 ± 8.9 vs +17.6 ± 12.3 points, p = 0.19) or UPDRS II (+9.3 ± 2.7 vs +7.4 ± 5.8 points, p = 0.16). Improvement in “on” time without dyskinesia was superior in asleep DBS (+6.4 ± 3.0 h/d vs +1.7 ± 1.2 h/d, p = 0.002). Quality of life scores improved in both groups (+18.8 ± 9.4 in awake, +8.9 ± 11.5 in asleep). Improvement in summary index (p = 0.004) and subscores for cognition (p = 0.011) and communication (p < 0.001) were superior in asleep DBS. Speech outcomes were superior in asleep DBS, both in category (+2.77 ± 4.3 points vs −6.31 ± 9.7 points (p = 0.0012) and phonemic fluency (+1.0 ± 8.2 points vs −5.5 ± 9.6 points, p = 0.038).Conclusions:Asleep DBS for PD improved motor outcomes over 6 months on par with or better than awake DBS, was superior with regard to speech fluency and quality of life, and should be an option considered for all patients who are candidates for this treatment.Clinicaltrials.gov identifier:NCT01703598.Classification of evidence:This study provides Class III evidence that for patients with PD undergoing DBS, asleep intraoperative CT imaging–guided implantation is not significantly different from awake microelectrode recording–guided implantation in improving motor outcomes at 6 months.
- Published
- 2017
12. Autonomic and electrocardiographic findings in Parkinson's disease
- Author
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Matthew Brodsky, Carlos Singer, Meilin Huang, Robert W. Hamill, Pei S. Wong, Roy Freeman, Ivan Bodis-Wollner, Sheng Luo, Aleksandar Videnovic, Barbara C. Tilley, David Simon, John L. Goudreau, Jacquelyn L. Bainbridge, Christopher H. Gibbons, and Michael J. Aminoff
- Subjects
Male ,medicine.medical_specialty ,Longitudinal study ,Parkinson's disease ,Disease ,030204 cardiovascular system & hematology ,Autonomic Nervous System ,Severity of Illness Index ,Article ,Antiparkinson Agents ,Electrocardiography ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Orthostatic vital signs ,0302 clinical medicine ,Heart Rate ,Internal medicine ,Heart rate ,medicine ,Humans ,Heart rate variability ,Longitudinal Studies ,Endocrine and Autonomic Systems ,business.industry ,Disease progression ,Age Factors ,Heart ,Parkinson Disease ,Middle Aged ,medicine.disease ,Electrocardiographic Finding ,Disease Progression ,Physical therapy ,Cardiology ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms and signs. Many reports suggest that diminished heart rate variability occurs early, even prior to the cardinal signs of PD. In a longitudinal study of PD, we evaluated whether heart rate variability (HRV) obtained using a 10 second ECG tracing, and the electrocardiographic QT-interval would be associated with PD severity and progression. Subjects were derived from a longitudinal study of 1741 individuals with early, stable PD. The severity of PD was measured using the global statistical test (GST). In a subset, the heart rate corrected QT-interval (QTcB) was calculated for each electrocardiogram (ECG). The HRV was measured for each ECG and then transformed to fit a normal distribution. The baseline analysis included 653 subjects, with 256 completing the 5-year follow up study. There was an association (P
- Published
- 2017
13. 5-HT 6 receptor blockade regulates primary cilia morphology in striatal neurons
- Author
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N. Cohenca, Alex Croicu, Adam J. Lesiak, Matthew Brodsky, Jane M. Sullivan, and John F. Neumaier
- Subjects
0301 basic medicine ,General Neuroscience ,Cilium ,Striatum ,Biology ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,Cytoplasm ,Organelle ,5-HT6 receptor ,Neurology (clinical) ,Serotonin ,Receptor ,Molecular Biology ,Neuroscience ,5-HT receptor ,Developmental Biology - Abstract
The 5-HT6 receptor has been implicated in a variety of cognitive processes including habitual behaviors, learning, and memory. It is found almost exclusively in the brain, is expressed abundantly in striatum, and localizes to neuronal primary cilia. Primary cilia are antenna-like, sensory organelles found on most neurons that receive both chemical and mechanical signals from other cells and the surrounding environment; however, the effect of 5-HT6 receptor function on cellular morphology has not been examined. We confirmed that 5-HT6 receptors were localized to primary cilia in wild-type (WT) but not 5-HT6 knockout (5-HT6KO) in both native mouse brain tissue and primary cultured striatal neurons then used primary neurons cultured from WT or 5-HT6KO mice to study the function of these receptors. Selective 5-HT6 antagonists reduced cilia length in neurons cultured from wild-type mice in a concentration and time-dependent manner without altering dendrites, but had no effect on cilia length in 5-HT6KO cultured neurons. Varying the expression levels of heterologously expressed 5-HT6 receptors affected the fidelity of ciliary localization in both WT and 5-HT6KO neurons; overexpression lead to increasing amounts of 5-HT6 localization outside of the cilia but did not alter cilia morphology. Introducing discrete mutations into the third cytoplasmic loop of the 5-HT6 receptor greatly reduced, but did not entirely eliminate, trafficking of the 5-HT6 receptor to primary cilia. These data suggest that blocking 5-HT6 receptor activity reduces the length of primary cilia and that mechanisms that regulate trafficking of 5-HT6 receptors to cilia are more complex than previously thought.
- Published
- 2017
14. Trial of dextromethorphan/quinidine to treat levodopa-induced dyskinesia in Parkinson's disease
- Author
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Nadine Knowles, John G. Nutt, Laura E. Pope, Stewart A. Factor, Anthony E. Lang, Joao Siffert, Susan H. Fox, Leonard Verhagen Metman, and Matthew Brodsky
- Subjects
0301 basic medicine ,Quinidine ,Levodopa-induced dyskinesia ,education.field_of_study ,business.industry ,Population ,Dextromethorphan ,Dextromethorphan/Quinidine ,Placebo ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Neurology ,Dyskinesia ,Anesthesia ,medicine ,Clinical endpoint ,Neurology (clinical) ,medicine.symptom ,business ,education ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background: Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia. Methods: PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2-week double-blind, crossover treatment periods, with intervening 2-week washout. After 14 days, a 2-hour intravenous levodopa-infusion was administered. Patient examinations were videotaped before infusion (“off” state) and every 30 minutes during and afterwards until patients returned to “off.” The primary endpoint was dyskinesia-severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area-under-curve scores (blinded expert rated). Additional endpoints included other dyskinesia/motor assessments, global measures of clinical-change, and adverse-events. Results: A total of 13 patients were randomized and completed the study (efficacy-evaluable population). Dyskinesia-severity was nonsignificantly lower with dextromethorphan/quinidine than placebo during infusion (area-under-curve 966.5 vs 1048.8; P = .191 [efficacy-evaluable patients]), and significantly lower in a post-hoc sensitivity analysis of the per-protocol-population (efficacy-evaluable patients with ≥ 80% study-drug-compliance, n = 12) when measured from infusion start to 4-hours post–infusion completion (area-under-curve 1585.0 vs 1911.3; P = .024). Mean peak dyskinesia decreased significantly from infusion-start to return to “off” (13.3 vs 14.9; P = .018 [efficacy-evaluable patients]). A total of 9 patients rated dyskinesia “much/very much improved” on dextromethorphan/quinidine versus 1-patient on placebo. Dextromethorphan/quinidine did not worsen PD-motor scores, was generally well tolerated, and was associated with more frequent adverse events. Conclusion: This study provides preliminary evidence of clinical benefit with dextromethorphan/quinidine for treating levodopa-induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. © 2017 International Parkinson and Movement Disorder Society
- Published
- 2017
15. Directional versus omnidirectional Deep Brain Stimulation: Results of a multi-cente prospective blinded crossover study
- Author
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Leonardo Almeida, Pablo Mir, Nestor D. Tomycz, Andrew Evans, Alfons Schnitzler, Binith Cheeran, Matthew Brodsky, Marta Blazquez, Winona Tse, Julie G. Pilitsis, Sergiu Groppa, Christian J. Hartmann, J. Jimenez-Shahed, L. Verhagen, Jan Vesper, Sean J. Nagel, Stefan Jun Groiss, Monika Pötter-Nerger, Fátima Carrillo, F. Defresne, Edward Karst, and R. Alvarez
- Subjects
Deep brain stimulation ,Neurology ,business.industry ,medicine.medical_treatment ,Medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Omnidirectional antenna ,Crossover study ,Biomedical engineering - Published
- 2020
16. Chrna5-Expressing Neurons in the Interpeduncular Nucleus Mediate Aversion Primed by Prior Stimulation or Nicotine Exposure
- Author
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Daniel W. Sparks, Evelyn K. Lambe, Eric E. Turner, Sanghavy Sivakumaran, Glenn Morton, Nailyam Nasirova, and Matthew Brodsky
- Subjects
0301 basic medicine ,Male ,Interpeduncular nucleus ,Nicotine ,Patch-Clamp Techniques ,Injections, Subcutaneous ,Interpeduncular Nucleus ,Recombinant Fusion Proteins ,Stimulation ,Mice, Transgenic ,Biology ,Receptors, Nicotinic ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Genes, Reporter ,mental disorders ,medicine ,Avoidance Learning ,Animals ,Research Articles ,Crosses, Genetic ,Mice, Knockout ,General Neuroscience ,Smoking ,Substance Withdrawal Syndrome ,Mice, Inbred C57BL ,Optogenetics ,Nicotinic acetylcholine receptor ,030104 developmental biology ,Habenula ,Nicotinic agonist ,Exploratory Behavior ,Cholinergic ,Female ,Neuroscience ,030217 neurology & neurosurgery ,Acetylcholine ,medicine.drug - Abstract
Genetic studies have shown an association between smoking and variation at the CHRNA5/A3/B4 gene locus encoding the α5, α3, and β4 nicotinic receptor subunits. The α5 receptor has been specifically implicated because smoking-associated haplotypes contain a coding variant in the CHRNA5 gene. The Chrna5/a3/b4 locus is conserved in rodents and the restricted expression of these subunits suggests neural pathways through which the reinforcing and aversive properties of nicotine may be mediated. Here, we show that, in the interpeduncular nucleus (IP), the site of the highest Chrna5 mRNA expression in rodents, electrophysiological responses to nicotinic acetylcholine receptor stimulation are markedly reduced in α5-null mice. IP neurons differ markedly from their upstream ventral medial habenula cholinergic partners, which appear unaltered by loss of α5. To probe the functional role of α5-containing IP neurons, we used BAC recombineering to generate transgenic mice expressing Cre-recombinase from the Chrna5 locus. Reporter expression driven by Chrna5Cre demonstrates that transcription of Chrna5 is regulated independently from the Chrna3/b4 genes transcribed on the opposite strand. Chrna5-expressing IP neurons are GABAergic and project to distant targets in the mesopontine raphe and tegmentum rather than forming local circuits. Optogenetic stimulation of Chrna5-expressing IP neurons failed to elicit physical manifestations of withdrawal. However, after recent prior stimulation or exposure to nicotine, IP stimulation becomes aversive. These results using mice of both sexes support the idea that the risk allele of CHRNA5 may increase the drive to smoke via loss of IP-mediated nicotine aversion.SIGNIFICANCE STATEMENT Understanding the receptors and neural pathways underlying the reinforcing and aversive effects of nicotine may suggest new treatments for tobacco addiction. Part of the individual variability in smoking is associated with specific forms of the α5 nicotinic receptor subunit gene. Here, we show that deletion of the α5 subunit in mice markedly reduces the cellular response to nicotine and acetylcholine in the interpeduncular nucleus (IP). Stimulation of α5-expressing IP neurons using optogenetics is aversive, but this effect requires priming by recent prior stimulation or exposure to nicotine. These results support the idea that the smoking-associated variant of the α5 gene may increase the drive to smoke via loss of IP-mediated nicotine aversion.
- Published
- 2018
17. Nigrosome 1 absence in de novo Parkinson disease
- Author
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David R. Pettersson, Jeffrey M. Pollock, John Grinstead, William D. Rooney, Matthew Brodsky, and David Lahna
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Red nucleus ,business.industry ,Cogwheel Rigidity ,Substantia nigra ,Parkinson Disease ,Disease ,Middle Aged ,Rest tremor ,Left wrist ,030218 nuclear medicine & medical imaging ,Substantia Nigra ,03 medical and health sciences ,0302 clinical medicine ,Cell bodies ,medicine ,Humans ,Neuronal degeneration ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
A 63-year-old man with 6 months of mild left hand rest tremor and bradykinesia and subtle left wrist cogwheel rigidity was diagnosed with idiopathic Parkinson disease (PD). The most profound neuronal degeneration in PD occurs in nigrosome 1, a lens-shaped substructure of the substantia nigra containing approximately 22,000 cell bodies in each hemi-midbrain, measuring 6 × 6 × 1 mm.1,2 A 7T MRI at the caudal level of red nucleus (figure, A) shows nigrosome 1 signal present in the left nigra and absent in the right, consistent with the clinically affected side. 7T MRI of a healthy 63-year-old with normal bilateral nigrosome 1 signal is shown for comparison (figure, B).
- Published
- 2018
18. Deconstructing 5-HT6 receptor effects on striatal circuit function
- Author
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Matthew Brodsky, Daniel Eskenazi, and John F. Neumaier
- Subjects
Male ,Receptor expression ,Genetic Vectors ,Striatum ,Dynorphin ,Medium spiny neuron ,Indirect pathway of movement ,Dynorphins ,Article ,Dopamine ,Dopamine receptor D2 ,medicine ,Animals ,Rats, Long-Evans ,Protein Precursors ,5-HT receptor ,Neurons ,General Neuroscience ,Enkephalins ,Rats ,Neostriatum ,nervous system ,Receptors, Serotonin ,Conditioning, Operant ,Psychology ,Neuroscience ,medicine.drug - Abstract
Medium spiny neurons (MSNs) constitute 95% of neurons in the dorsal striatum subdivided into direct (striatonigral) and indirect (striatopallidal) pathways. Whereas D1 and D2 receptors and several neuropeptides, including dynorphin and enkephalin, are differentially expressed in these neurons, 5-hydroxytryptamine 6 receptors (5-HT6) are expressed in both pathways. Previous results demonstrate that concurrent 5-HT6 receptor overexpression in MSNs of both pathways in the dorsomedial striatum (DMS) interferes with instrumental learning and that 5-HT6 overexpression in the dorsolateral striatum (DLS) relieves rats from inflexible habitual behaviors. We hypothesized that 5-HT6 receptor-mediated co-activation of both pathways interferes with the differential activation/inhibition of direct/indirect pathways by dopamine. To test this idea, we cloned novel viral vectors to selectively overexpress 5-HT6 receptors in direct or indirect pathway MSNs to deconstruct their role in modulating instrumental learning and habitual responding. We found that increasing 5-HT6 receptor expression in either direct or indirect pathway MSNs of the posterior DMS selectively enhanced or impaired initial acquisition of a discrete instrumental learning task respectively, though all rats were ultimately able to learn the task. In a separate set of experiments, 5-HT6 receptor overexpression in indirect pathway MSNs of the DLS facilitated behavioral flexibility in rats overtrained on a repetitive pressing task using a variable interval schedule of reinforcement, during an omission contingency training session and subsequent probe testing. Together these findings further the notion that 5-HT6 signaling causes balanced activation of opposing MSN pathways by serotonin in sub-regions of the dorsal striatum allowing for more reflective modalities of behavior.
- Published
- 2015
19. Author response: Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease
- Author
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Matthew Brodsky
- Subjects
medicine.medical_specialty ,Deep brain stimulation ,business.industry ,Deep Brain Stimulation ,medicine.medical_treatment ,Controlled Oral Word Association Test ,Parkinson Disease ,Audiology ,Neurosurgical Procedures ,03 medical and health sciences ,Fluency ,0302 clinical medicine ,medicine ,Humans ,030212 general & internal medicine ,Neurology (clinical) ,Wakefulness ,business ,Pre and post ,030217 neurology & neurosurgery - Abstract
We thank Dr. Troster for the thoughtful comments on our article.1 To clarify, Controlled Oral Word Association Test (COWAT) scores were standard scores instead of raw word counts, reflected in the means and SDs pre and post deep brain stimulation (DBS) for categorical fluency (awake pre-DBS: 47.95 ± 7.28, awake post-DBS: 42.94 ± 10.45; asleep pre-DBS: 97.61 ± 17.1, asleep post-DBS: 96.95 ± 15.5) and phonemic fluency (awake pre-DBS: 47.95 ± 7.28, awake post-DBS: 42.94 ± 10.45; asleep pre-DBS: 97.61 ± 17.1, asleep post-DBS: 96.95 ± 15.5).
- Published
- 2018
20. 5-HT
- Author
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Matthew, Brodsky, Adam J, Lesiak, Alex, Croicu, Nathalie, Cohenca, Jane M, Sullivan, and John F, Neumaier
- Subjects
Mice, Knockout ,Neurons ,Sulfonamides ,Time Factors ,Dose-Response Relationship, Drug ,Pyridines ,Gene Expression ,Corpus Striatum ,Piperazines ,Article ,Serotonin Receptor Agonists ,Mice, Inbred C57BL ,Methylamines ,Receptors, Serotonin ,Animals ,Cilia ,Serotonin Antagonists ,Cells, Cultured - Abstract
The 5-HT6 receptor has been implicated in a variety of cognitive processes including habitual behaviors, learning, and memory. It is found almost exclusively in the brain, is expressed abundantly in striatum, and localizes to neuronal primary cilia. Primary cilia are antenna-like, sensory organelles found on most neurons that receive both chemical and mechanical signals from other cells and the surrounding environment; however, the effect of 5-HT6 receptor function on cellular morphology has not been examined. We confirmed that 5-HT6 receptors were localized to primary cilia in wild-type (WT) but not 5-HT6 knockout (5-HT6KO) in both native mouse brain tissue and primary cultured striatal neurons then used primary neurons cultured from WT or 5-HT6KO mice to study the function of these receptors. Selective 5-HT6 antagonists reduced cilia length in neurons cultured from wild-type mice in a concentration and time-dependent manner without altering dendrites, but had no effect on cilia length in 5-HT6KO cultured neurons. Varying the expression levels of heterologously expressed 5-HT6 receptors affected the fidelity of ciliary localization in both WT and 5-HT6KO neurons; overexpression lead to increasing amounts of 5-HT6 localization outside of the cilia but did not alter cilia morphology. Introducing discrete mutations into the third cytoplasmic loop of the 5-HT6 receptor greatly reduced, but did not entirely eliminate, trafficking of the 5-HT6 receptor to primary cilia. These data suggest that blocking 5-HT6 receptor activity reduces the length of primary cilia and that mechanisms that regulate trafficking of 5-HT6 receptors to cilia are more complex than previously thought.
- Published
- 2016
21. Trial of dextromethorphan/quinidine to treat levodopa-induced dyskinesia in Parkinson's disease
- Author
-
Susan H, Fox, Leonard Verhagen, Metman, John G, Nutt, Matthew, Brodsky, Stewart A, Factor, Anthony E, Lang, Laura E, Pope, Nadine, Knowles, and João, Siffert
- Subjects
Male ,Dyskinesia, Drug-Induced ,Cross-Over Studies ,Parkinson Disease ,Pilot Projects ,Middle Aged ,Dextromethorphan ,Quinidine ,Antiparkinson Agents ,Levodopa ,Double-Blind Method ,Outcome Assessment, Health Care ,Humans ,Drug Therapy, Combination ,Female ,Enzyme Inhibitors ,Excitatory Amino Acid Antagonists ,Aged - Abstract
Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia.PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2-week double-blind, crossover treatment periods, with intervening 2-week washout. After 14 days, a 2-hour intravenous levodopa-infusion was administered. Patient examinations were videotaped before infusion ("off" state) and every 30 minutes during and afterwards until patients returned to "off." The primary endpoint was dyskinesia-severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area-under-curve scores (blinded expert rated). Additional endpoints included other dyskinesia/motor assessments, global measures of clinical-change, and adverse-events.A total of 13 patients were randomized and completed the study (efficacy-evaluable population). Dyskinesia-severity was nonsignificantly lower with dextromethorphan/quinidine than placebo during infusion (area-under-curve 966.5 vs 1048.8; P = .191 [efficacy-evaluable patients]), and significantly lower in a post-hoc sensitivity analysis of the per-protocol-population (efficacy-evaluable patients with ≥ 80% study-drug-compliance, n = 12) when measured from infusion start to 4-hours post-infusion completion (area-under-curve 1585.0 vs 1911.3; P = .024). Mean peak dyskinesia decreased significantly from infusion-start to return to "off" (13.3 vs 14.9; P = .018 [efficacy-evaluable patients]). A total of 9 patients rated dyskinesia "much/very much improved" on dextromethorphan/quinidine versus 1-patient on placebo. Dextromethorphan/quinidine did not worsen PD-motor scores, was generally well tolerated, and was associated with more frequent adverse events.This study provides preliminary evidence of clinical benefit with dextromethorphan/quinidine for treating levodopa-induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. © 2017 International Parkinson and Movement Disorder Society.
- Published
- 2016
22. Recombinase-Driver Rat Lines: Tools, Techniques, and Optogenetic Application to Dopamine-Mediated Reinforcement
- Author
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Soo Yeun Lee, Garret D. Stuber, Thomas J. Davidson, Elizabeth E. Steinberg, Patricia H. Janak, Saemi L. Cho, Ilana B. Witten, Karl Deisseroth, Matthew Brodsky, Charu Ramakrishnan, Shiaoching Gong, Kay M. Tye, Kelly A. Zalocusky, and Ofer Yizhar
- Subjects
Male ,Cell type ,Optics and Photonics ,Reinforcement Schedule ,Tyrosine 3-Monooxygenase ,Transgene ,Dopamine ,Neuroscience(all) ,Cre recombinase ,Action Potentials ,Biology ,Optogenetics ,In Vitro Techniques ,Article ,Choline O-Acetyltransferase ,Self Stimulation ,Transduction, Genetic ,medicine ,Recombinase ,Animals ,Neurons ,Tyrosine hydroxylase ,Integrases ,Opsins ,General Neuroscience ,Ventral Tegmental Area ,Choline acetyltransferase ,Rats ,Ventral tegmental area ,medicine.anatomical_structure ,Gene Expression Regulation ,Conditioning, Operant ,Rats, Transgenic ,Neuroscience ,Reinforcement, Psychology - Abstract
Currently there is no general approach for achieving specific optogenetic control of genetically defined cell types in rats, which provide a powerful experimental system for numerous established neurophysiological and behavioral paradigms. To overcome this challenge we have generated genetically restricted recombinase-driver rat lines suitable for driving gene expression in specific cell types, expressing Cre recombinase under the control of large genomic regulatory regions (200-300 kb). Multiple tyrosine hydroxylase (Th)::Cre and choline acetyltransferase (Chat)::Cre lines were produced that exhibited specific opsin expression in targeted cell types. We additionally developed methods for utilizing optogenetic tools in freely moving rats and leveraged these technologies to clarify the causal relationship between dopamine (DA) neuron firing and positive reinforcement, observing that optical stimulation of DA neurons in the ventral tegmental area (VTA) of Th::Cre rats is sufficient to support vigorous intracranial self-stimulation (ICSS). These studies complement existing targeting approaches by extending the generalizability of optogenetics to traditionally non-genetically-tractable but vital animal models.
- Published
- 2011
- Full Text
- View/download PDF
23. A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease
- Author
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Margaret Marie Cox, Stephanie Sendek, Margaret F. Turk, Julie H. Carter, Susan C. Fagan, Lorelei Derwent, Oksana Suchowersky, Jay S. Schneider, Linda Paul, Gwyn Vernon, Stephen Gollomp, Karl Kieburtz, Debbie Baker, I. Van Bodis-Wollner, Germaine McInnes, Marian A. Perez, G. Webster Ross, Katharine Pabst, Jorge L. Juncos, Chad W. Christine, Jessie Roth, Joseph M. Savitt, Peter A LeWitt, Hubert H. Fernandez, Matthew Brodsky, Mark F. Lew, Jay M. Gorell, Natividad R. Stover, Paulo Guimaraes, Andrew Feigin, Anita Blenke, Martha Nance, Elizabeth Hayes, Andrew Siderowf, W.R. Wayne Martin, Tammie Kelsey, Susan Bennett, Sharon McCarthy, Charles H. Adler, Beverly Olsen, Pauline LeBlanc, Richard B. Dewey, Rodger J. Elble, Richard S. Burns, Carlos Singer, Amy Parsons, John W. Taylor, Tracy Stewart, Maryan DeAngelis, Barbara C. Tilley, William J. Weiner, Brad A. Racette, Wendy R. Galpern, Michael J. Aminoff, Kapil D. Sethi, Jayaraman Rao, Robert A. Hauser, Debbie Fraser, Connie Kawai, David Coffey, Kelly E. Lyons, Kristine Wernette, Becky Dunlop, Holly Delgado, Marlene Lind, Rajesh Pahwa, Chris Weaver, Ray L. Watts, Patricia Deppen, Ryan J. Uitti, Marwan N. Sabbagh, Lynn Marlor, Joann Belden, Burton L. Scott, Theresa McClain, Roger L. Albin, John Y. Fang, Zoran Obradov, Yuko Y. Palesch, Maureen Cook, Pamela Andrews, Jeana Jaglin, Joanne Wojcieszek, Mary Louise Musante Weeks, Susan Peterson, James H. Bower, Maureen A. Leehey, Joanne Field, Lisa M. Shulman, Caroline M. Tanner, Jacob I. Sage, Jordan J. Elm, Joseph Jankovic, Patrick D. Mauldin, Aileen Shinaman, Peng Huang, G. Frederick Wooten, Alicia Brocht, Gordon H. Brown, Peggy Roberge, Dorothy Shearon, Buff Dill, Margaret F. Keller, Charlene Young, Christine Hunter, Janis M. Miyasaki, Susan Torgrimson, Cornelia Kamp, Brigid Hayward, Christopher G. Goetz, Emily Kosa, Marilyn Flewellen, David Simon, Rebecca McMurray, Sue Reichwein, Jacci Bainbridge, Robert W. Hamill, Stephanie Terashita, Kathleen M. Shannon, Frederick Wooten, Danna Jennings, Shana Krstevska, and Bernard Ravina
- Subjects
Male ,medicine.medical_specialty ,Future studies ,Neurology ,Ubiquinone ,Coenzymes ,Disease ,Placebo ,Tacrolimus ,law.invention ,chemistry.chemical_compound ,Double-Blind Method ,Randomized controlled trial ,law ,Rating scale ,Internal medicine ,Humans ,Medicine ,Aged ,Coenzyme Q10 ,business.industry ,Headache ,Nausea ,Parkinson Disease ,Middle Aged ,Clinical trial ,chemistry ,Physical therapy ,Female ,Neurology (clinical) ,business - Abstract
Objective: To determine if future studies of coenzyme Q10 and GPI-1485 in Parkinson disease (PD) may be warranted. Methods: We conducted a randomized, double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in early untreated PD using placebo data from the DATATOP study to establish the futility threshold. Results: The primary outcome measure (change in total Unified Parkinson's Disease Rating Scale scores over 1 year) did not meet the prespecified criteria for futility for either agent. Secondary analyses using calibration controls and other more recent placebo data question the appropriateness of the predetermined definition of futility, and suggest that a more restrictive threshold may be needed. Conclusions: Coenzyme Q10 and GPI-1485 may warrant further study in Parkinson disease, although the data are inconsistent. Additional factors (cost, availability of other agents, more recent data on placebo outcomes, other ongoing trials) should also be considered in the selection of agents for Phase III studies. NEUROLOGY 2007;68:20-28
- Published
- 2007
24. Striatal 5-HT6 Receptors Regulate Cocaine Reinforcement in a Pathway-Selective Manner
- Author
-
Matthew Brodsky, Sunila G. Nair, Denis Smirnov, John F. Neumaier, and Alec W Gibson
- Subjects
0301 basic medicine ,Male ,Enkephalin ,Receptor expression ,Conditioning, Classical ,Self Administration ,Nucleus accumbens ,Pharmacology ,Medium spiny neuron ,Nucleus Accumbens ,03 medical and health sciences ,0302 clinical medicine ,Cocaine ,Dopamine ,medicine ,Animals ,Rats, Long-Evans ,Receptor ,Neurons ,Conditioned place preference ,Psychiatry and Mental health ,030104 developmental biology ,Receptors, Serotonin ,Conditioning, Operant ,Original Article ,Serotonin ,Psychology ,Reinforcement, Psychology ,030217 neurology & neurosurgery ,Locomotion ,medicine.drug - Abstract
The nucleus accumbens (NAc) in the ventral striatum integrates many neurochemical inputs including dopamine and serotonin projections from midbrain nuclei to modulate drug reward. Although D1 and D2 dopamine receptors are differentially expressed in the direct and indirect pathway medium spiny neurons (dMSNs and iMSNs, respectively), 5-HT6 receptors are expressed in both pathways, more strongly than anywhere else in the brain, and are an intriguing target for neuropsychiatric disorders. In the present study, we used viral vectors utilizing dynorphin or enkephalin promoters to drive expression of 5-HT6 receptors or green fluorescent protein (GFP) selectively in the dMSNs or iMSNs of the NAc shell. Rats were then trained to self-administer cocaine. Increased 5-HT6 receptor expression in dMSNs did not change any parameter of cocaine self-administration measured. However, increasing 5-HT6 receptors in iMSNs reduced the amount of cocaine self-administered under fixed-ratio schedules, especially at low doses, increased the time to the first response and the length of the inter-infusion interval, but did not alter motivation as measured by progressive ratio 'break point' analysis. Modeling of cocaine pharmacokinetics in NAc showed that increased 5-HT6 receptors in iMSNs reduced the rat's preferred tissue cocaine concentration at each dose. Finally, increased 5-HT6 receptors in iMSNs facilitated conditioned place preference for a low dose of cocaine. We conclude that 5-HT6 receptors in iMSNs of NAcSh increase the sensitivity to the reinforcing properties of cocaine, particularly at low doses, suggesting that these receptors may be a therapeutic target for the treatment of cocaine addiction.
- Published
- 2015
25. RiboTag is a flexible tool for measuring the translational state of targeted cells in heterogeneous cell cultures
- Author
-
John F. Neumaier, Adam J. Lesiak, and Matthew Brodsky
- Subjects
Cell type ,Mice, Transgenic ,Computational biology ,Biology ,Transfection ,General Biochemistry, Genetics and Molecular Biology ,Article ,Gene expression ,Animals ,Cells, Cultured ,Regulation of gene expression ,Neurons ,fungi ,Reverse Transcription ,Molecular biology ,Coculture Techniques ,Mice transgenic ,Mice, Inbred C57BL ,Gene Expression Regulation ,Cell culture ,Polyribosomes ,Protein Biosynthesis ,Coculture Technique ,RNA ,Neuroglia ,Biotechnology ,Plasmids - Abstract
Primary neuronal cultures are a useful tool for measuring pharmacological- and transgene-regulated gene expression; however, accurate measurements can be confounded by heterogeneous cell types and inconsistent transfection efficiency. Here we describe our adaptation of a ribosomal capture strategy that was designed to be used in transgenic mice expressing tagged ribosomal subunits (RiboTag) in specific cell types, thereby allowing measurement of translating RNAs from desired cell types within complex tissues. Using this strategy we were able to isolate and analyze neuron-specific RNA despite the presence of glia by co-transfecting experimental plasmids with plasmids that selectively express RiboTag in neurons. RiboTag immunoprecipitation was capable of recovering high integrity RNA from small numbers of transfected cells that can then be interrogated by a variety of methods (e.g., RT-qPCR, PCR array, RNA-Seq) and compared with basal RNA expression of the entire culture. Additionally, we demonstrate how co-transfection of RiboTag with small hairpin RNA (shRNA) constructs can validate and accurately assess the degree of gene expression knockdown, and how RiboTag can be used to measure receptor-mediated gene regulation with transiently expressed designer receptors exclusively activated by designer drugs (DREADDs). RiboTag co-transfection represents a convenient and powerful tool to isolate RNA from a specific subset of cultured cells with a variety of applications for experiments in vitro.
- Published
- 2015
26. OFF-offrebound dyskinesia in subthalamic nucleus deep brain stimulation of Parkinson's disease
- Author
-
John G. Nutt, Matthew Brodsky, and Penelope Hogarth
- Subjects
Male ,Parkinson's disease ,Deep brain stimulation ,Deep Brain Stimulation ,medicine.medical_treatment ,Central nervous system ,Neurological disorder ,Antiparkinson Agents ,Levodopa ,Stereotaxic Techniques ,Central nervous system disease ,Degenerative disease ,Subthalamic Nucleus ,Secondary Prevention ,otorhinolaryngologic diseases ,medicine ,Humans ,Dominance, Cerebral ,Neurologic Examination ,Dyskinesias ,business.industry ,Carbidopa ,Parkinson Disease ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Magnetic Resonance Imaging ,Corpus Striatum ,Electrodes, Implanted ,Substance Withdrawal Syndrome ,nervous system diseases ,Subthalamic nucleus ,surgical procedures, operative ,medicine.anatomical_structure ,nervous system ,Neurology ,Dyskinesia ,Anesthesia ,Drug Therapy, Combination ,Neurology (clinical) ,medicine.symptom ,business ,therapeutics - Abstract
A 61-year-old man with Parkinson's disease (PD), motor fluctuations, and dyskinesias underwent bilateral implantation of deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN). One month after surgery, DBS was optimized to bilateral monopolar settings at the most proximal electrode just superior to the STN, which improved motor fluctuations and dyskinesias. At several postoperative evaluations off medications overnight, both stimulators were turned off and within 60 seconds he developed severe dyskinesias. When the stimulators were turned back on, the dyskinesias soon resolved. This article is a first report of a unique pattern of rebound-type dyskinesia that occurred in the off medication state produced by stopping STN DBS.
- Published
- 2006
27. Neurologic drug–psychotropic drug update
- Author
-
James J. Strain, Carol Himelein, Anwarul Karim, Gina Caliendo, Matthew Brodsky, and R.Sandlin Lowe
- Subjects
Drug ,MedWatch ,medicine.medical_specialty ,business.industry ,media_common.quotation_subject ,MEDLINE ,General Medicine ,Carbamazepine ,Drug interaction ,Mood ,Psychotropic drug ,mental disorders ,medicine ,Formulary ,Psychiatry ,business ,medicine.drug ,media_common - Abstract
It is essential that both the neurologist and the psychiatrist be aware of the neurology drug–psychotropic drug interactions because neurologists prescribe many psychotropic medications and psychiatric consultants often recommend the use of psychotropic drugs for neurology patients. Six methods of examining drug–drug interactions were employed: 1) PubMed (MEDLINE); 2) Hanston's Drug Interaction Analysis and Management Text (July 2001 quarterly updated version); 3) Drug Interactions Facts (quarterly updated version through July 2001); 4) Micromedex Drug-dex; 5) American Hospital Formulary Service Drug Information; 6) Food and Drug Administration (MedWatch) Dear Doctor Letters and new labeling. Over eighty important interactions of significance level 1 (major), or significance level 2 (minor) were found. Furthermore, over one-third of the neurologist's most commonly administered medications were those also employed by the psychiatrist, but not necessarily for the same reason, e.g., carbamazepine, for seizure control (neurologist) or mood stabilization (psychiatrist).
- Published
- 2003
28. Comparison of three methods for identifying medical drug-psychotropic drug interactions
- Author
-
Nien Mu Chiu, Gina Caliendo, James J. Strain, Matthew Brodsky, and Anwarul Karim
- Subjects
Drug ,Hand Held Computer ,Gerontology ,Psychotropic Drugs ,business.product_category ,business.industry ,media_common.quotation_subject ,Psychotropic medication ,Psychiatry and Mental health ,Psychotropic drug ,Human–computer interaction ,Laptop ,Humans ,Medicine ,Drug Interactions ,Software system ,Hard copy ,business ,Software ,Central Nervous System Agents ,media_common ,Desk - Abstract
Three methods for examining drug-drug interactions were compared to understand advantages and disadvantages of each: ePocrates; Interact; The Mount Sinai multiple source for the evaluation of drug-drug interactions (MS). ePocrates is a commonly employed software system utilized in a hand held computer, the PalmPilot. Interact is on a CD-ROM, and promoted by the American Psychiatric Association Press. The MS system was developed by the authors and utilizes six separate references sources to ascertain the presence and significance of drug-drug interactions. Commonly prescribed neurology and psychotropic medication interactions were compared using the three systems. ePocrates did not list the significance level of the interaction, e.g., (major, moderate, minor), often did not include a mechanism of action, and several commonly employed medications were not included. It did permit examining several drugs at the same time, and was easily carried on the person of the physician. Interact often contained old references, several drugs were not included, was not adapted to a hand held computer format, and had no update since 1999. The MS system listed level of significance, provided mechanism of action, and advice to the practitioner including recommendations. It is not portable, requiring a laptop or desk top computer or hard copy, and only searches one drug at a time. It is hoped that the advantages of each of these three systems may be incorporated into systems of the future.
- Published
- 2002
29. Neuropsychological changes following deep brain stimulation surgery for Parkinson's disease: comparisons of treatment at pallidal and subthalamic targets versus best medical therapy
- Author
-
Frances M. Weaver, Jamal Taha, Roy A.E. Bakay, Claudia S. Moy, Tom Erikson, Virginia Janovsky, Alice Cugley, Monica Volz, Grant D. Huang, Penelope Hogarth, Tammy Harris, Romay Franks, Kim J. Burchiel, Dolores Ippolito, Carol Fye, Mary Lloyd, Jeffrey S. Kreutzer, Kathryn L. Holloway, William Koller, Gail A. Kang, Philip A. Starr, Marilyn Garin, Mario F. Mendez, Robert Hall, Gatana Stoner, Jill Heemskerk, Louis Fiore, Tina Conn, Mark Baron, Margaret Schenkman, Rajesh Pahwa, Jyh Gong Hou, Robert Woolson, Domenic J. Reda, Vincent Calabrese, Ken Bukowski, Miriam Hirsch, Jamye Valotta, Matthew Brodsky, Ping Luo, Kenneth A. Follett, Ali Samii, Eugene C. Lai, Theresa Simon, Linda Fincher, Daniel Storzbach, Rebecca Warker, Sharon Matzek, Ligaya Ordonez, Kwan Hur, Richard J. Simpson, Elizabeth Meyn, Mary Matthews, William J. Marks, Crystal L. Harris, Paul J. Moberg, Eva Henry, Aliya Sarwar, Pamela Willson, Constance Ward, Rosemarie De Nicolo, Indu Subramanian, Wes Morrow, Antonio A.F. De Salles, John E. Duda, Jan Motyka, Jurg Jaggi, Keiko Mimura, George McCabe, Lisette Bunting-Perry, William Gagne, Elizabeth M. Soety, Susan O'Connor, Gordon H. Baltuch, Matthew B. Stern, Paul Sheehy, Susan Loehner, Tammy Barnett, Nanette Eubank, Amy Colcher, Jorge Eller, K. F. Chairpersons, Heather Maccarone, Tammy Searles, William Carne, Jeff Kraakevik, Julia Buckelew, Kelli Massey-Makhoul, Michele K. York, Heidi Watson, Bharat Thakkar, Robert G. Holloway, Ronald T. Seel, Timothy O'Leary, Zeba Vanek, Jeff M. Bronstein, Farah Atassi, Stacy Horn, Cecilia Bello, Donna Smith, Jill L. Ostrem, Paul S. Larson, Emad Farag, Rick Chappell, Kim Carlson, John Ragland, Susan Heath, Mariann Haselman, Robert P. Hart, John G. Nutt, Joyce Jimenez, Galit Kleiner-Fisman, Usha Vasthare, Oren Sagher, Elaine Lanier, Alexander I. Tröster, Kevin Stroupe, Gordon Campbell, and Johannes C. Rothlind
- Subjects
Adult ,Male ,medicine.medical_specialty ,Deep brain stimulation ,Parkinson's disease ,medicine.medical_treatment ,Deep Brain Stimulation ,Neuropsychological Tests ,Globus Pallidus ,Executive Function ,Physical medicine and rehabilitation ,Cognition ,Quality of life ,Subthalamic Nucleus ,medicine ,Humans ,Prospective Studies ,Cognitive decline ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,Neuropsychology ,Cognitive flexibility ,Parkinson Disease ,Neuropsychological test ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Subthalamic nucleus ,surgical procedures, operative ,Treatment Outcome ,Physical therapy ,Disease Progression ,Quality of Life ,Surgery ,Female ,Neurology (clinical) ,Psychology ,Psychomotor Performance ,Follow-Up Studies - Abstract
Background Deep brain stimulation (DBS) improves motor symptoms in Parkinson9s disease (PD), but questions remain regarding neuropsychological decrements sometimes associated with this treatment, including rates of statistically and clinically meaningful change, and whether there are differences in outcome related to surgical target. Methods Neuropsychological functioning was assessed in patients with Parkinson9s disease (PD) at baseline and after 6 months in a prospective, randomised, controlled study comparing best medical therapy (BMT, n=116) and bilateral deep brain stimulation (DBS, n=164) at either the subthalamic nucleus (STN, n=84) or globus pallidus interna (GPi, n=80), using standardised neuropsychological tests. Measures of functional outcomes were also administered. Results Comparison of the two DBS targets revealed few significant group differences. STN DBS was associated with greater mean reductions on some measures of processing speed, only one of which was statistically significant in comparison with stimulation of GPi. GPi DBS was associated with lower mean performance on one measure of learning and memory that requires mental control and cognitive flexibility. Compared to the group receiving BMT, the combined DBS group had significantly greater mean reductions at 6-month follow-up in performance on multiple measures of processing speed and working memory. After calculating thresholds for statistically reliable change from data obtained from the BMT group, the combined DBS group also displayed higher rates of decline in neuropsychological test performance. Among study completers, 18 (11%) study participants receiving DBS displayed reliable decline by multiple indicators in two or more cognitive domains, a significantly higher rate than in the BMT group (3%). This multi-domain cognitive decline was associated with less beneficial change in subjective ratings of everyday functioning and quality of life (QOL). The multi-domain cognitive decline group continued to function at a lower level at 24-month follow-up. Conclusions In those with PD, the likelihood of significant decline in neuropsychological functioning increases with DBS, affecting a small minority of patients who also appear to respond less optimally to DBS by other indicators of QOL. Trial registration number NCT00056563 and NCT01076452.
- Published
- 2014
30. Deep brain stimulation versus best medical therapy for PD
- Author
-
Matthew Brodsky and John G. Nutt
- Subjects
medicine.medical_specialty ,Deep brain stimulation ,business.industry ,medicine.medical_treatment ,Disease ,nervous system diseases ,Cellular and Molecular Neuroscience ,surgical procedures, operative ,Quality of life (healthcare) ,Physical therapy ,medicine ,Neurology (clinical) ,Adverse effect ,business ,Medical therapy - Abstract
A new study indicates that deep brain stimulation (DBS) plus best medical therapy markedly improves quality of life of patients with advanced Parkinson disease compared with best medical therapy alone. The frequency of serious adverse events related to DBS was similar to that reported in other DBS trials, underscoring the need for careful patient selection and counseling for this invasive therapy.
- Published
- 2010
31. GDNF in treatment of Parkinson's disease: response to editorial
- Author
-
Anthony E Lang, J William Langston, A Jon Stoessl, Matthew Brodsky, David J Brooks, Vijay Dhawan, William J Elias, Andres M Lozano, Elena Moro, John G Nutt, Mark Stacy, Dennis Turner, and G Frederick Wooten
- Subjects
Neurology (clinical) - Published
- 2006
32. Cholinergic Interneurons Control Local Circuit Activity and Cocaine Conditioning
- Author
-
Ilana B. Witten, Matthew Brodsky, Rohit Prakash, Polina Anikeeva, Ilka Diester, Karl Deisseroth, Viviana Gradinaru, Charu Ramakrishnan, and Shih Chun Lin
- Subjects
Transgene ,Action Potentials ,Mice, Transgenic ,Motor Activity ,Optogenetics ,Biology ,Nucleus accumbens ,Article ,Nucleus Accumbens ,Choline O-Acetyltransferase ,Mice ,Cocaine ,Reward ,Interneurons ,Conditioning, Psychological ,medicine ,Animals ,Gene silencing ,Cholinergic neuron ,Acetylcholine receptor ,Neurons ,Multidisciplinary ,Behavior, Animal ,Anatomy ,Synaptic Potentials ,Acetylcholine ,Inhibitory Postsynaptic Potentials ,nervous system ,Cholinergic ,Neuroscience ,medicine.drug - Abstract
Few But Powerful Drug activation of the different types of acetylcholine receptors in cholinergic neurons often generates opposing or conflicting effects. Using optogenetic techniques in transgenic mice, Witten et al. (p. 1677 ) investigated the function of a rather enigmatic subpopulation of cholinergic neurons, the giant interneurons of the nucleus accumbens. Their excitation paradoxically reduced neighboring medium spiny neuron firing, while their inhibition increased medium spiny neuron firing. Furthermore, the giant interneurons were directly activated by cocaine, and silencing their drug-induced activity during cocaine exposure in freely behaving animals disrupted cocaine reward.
- Published
- 2010
33. Effects of a Dopamine Agonist on the Pharmacodynamics of Levodopa in Parkinson Disease
- Author
-
Matthew Brodsky, John G. Nutt, and Byung S. Park
- Subjects
Adult ,Male ,Dyskinesia, Drug-Induced ,Levodopa ,Placebo ,Risk Assessment ,Dopamine agonist ,Article ,Pramipexole ,Double-Blind Method ,Arts and Humanities (miscellaneous) ,Outcome Assessment, Health Care ,medicine ,Humans ,Benzothiazoles ,Infusions, Intravenous ,Aged ,Aged, 80 and over ,Cross-Over Studies ,business.industry ,Area under the curve ,Brain ,Drug Synergism ,Parkinson Disease ,Middle Aged ,Crossover study ,nervous system diseases ,Treatment Outcome ,Dyskinesia ,Anesthesia ,Dopamine Agonists ,Drug Therapy, Combination ,Female ,Pramipexole Dihydrochloride ,Neurology (clinical) ,medicine.symptom ,business ,medicine.drug - Abstract
Background Treatment of Parkinson disease commonly includes levodopa and dopamine agonists; however, the interaction of these 2 drugs is poorly understood. Objective To examine the effects of a dopamine agonist on the motor response to levodopa. Design Double-blind, randomized, placebo-controlled, crossover clinical trial. Setting Ambulatory academic referral center. Patients Thirteen patients with idiopathic Parkinson disease taking levodopa and experiencing motor fluctuations and dyskinesia. Interventions Eligible individuals were randomly assigned to receive pramipexole dihydrochloride or placebo for 4 weeks followed by a 2-hour intravenous levodopa infusion on consecutive days at 2 rates and with blinded assessments. They were then crossed over to the alternate oral therapy for 4 weeks followed by levodopa infusion and reassessment. Main Outcome Measures Change in finger-tapping speed, measured using the area under the curve (AUC) for finger taps per minute across time; peak finger-tapping speed; duration of response; time to “ON” (defined as a 10% increase in finger-tapping speed above baseline); walking speed; and dyskinesia AUC. Results Pramipexole with levodopa infusion increased finger-tapping speed beyond the change in baseline by a mean (SE) of 170 (47.2) per minute × minutes ( P = .006) and more than doubled the AUC for finger-tapping speed. Pramipexole increased peak finger-tapping speed by a mean (SE) of 18 (8.5) taps per minute ( P = .02) and improved mean (SE) walking speed (15.9 [0.70] vs 18.9 [0.70] seconds, P = .004). Pramipexole prolonged duration of response after levodopa infusion and shortened time to ON. Pramipexole increased mean (SE) baseline dyskinesia scores (26.0 [5.85] vs 12.1 [5.85] points, P = .05) and peak dyskinesia scores with levodopa infusion. Conclusions Pramipexole augmented the motor response to levodopa beyond a simple additive effect and increased the severity of levodopa-induced dyskinesia. When considering a combination of these therapies, an appropriate balance should be maintained regarding gain of motor function vs worsening of dyskinesia. Trial Registration clinicaltrials.gov Identifier:NCT00666653
- Published
- 2010
34. Long-term efficacy and safety of botulinum toxin type A (Dysport) in cervical dystonia
- Author
-
Eric Molho, Matthew Brodsky, Joseph Jankovic, Allison Brashear, Olga Orlova, Daniel D. Truong, Sofia Timerbaeva, and Mark F. Lew
- Subjects
Adult ,Male ,Visual analogue scale ,Spasmodic Torticollis ,Placebo ,Severity of Illness Index ,law.invention ,Disability Evaluation ,Young Adult ,Randomized controlled trial ,Double-Blind Method ,law ,Rating scale ,Severity of illness ,medicine ,Humans ,Cervical dystonia ,Longitudinal Studies ,Botulinum Toxins, Type A ,Adverse effect ,Torticollis ,Aged ,Pain Measurement ,Dose-Response Relationship, Drug ,Middle Aged ,medicine.disease ,Treatment Outcome ,Neurology ,Neuromuscular Agents ,Anesthesia ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,Drug Monitoring ,Injections, Intraocular ,Psychology - Abstract
The aim of this study was to evaluate the efficacy and safety of intramuscular (IM) administration of botulinum toxin type A (Dysport((R)), Ipsen Biopharm Ltd.) for the treatment of cervical dystonia (CD) and the long-term safety and efficacy of repeated treatments. During the randomized, double-blind, placebo-controlled phase patients were randomized to 500 units Dysport (n = 55) or placebo (n = 61). Efficacy assessments included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total and subscale scores, visual analogue scale (VAS) for pain, subject/investigator's VAS for symptom assessments. Patients completing the double-blind treatment could enter an open-label extension phase and receive up to 4 additional Dysport treatments. Dysport produced a significant decrease from baseline in mean (+/-SE) TWSTRS total scores compared with placebo at Week 4 (primary efficacy endpoint; -15.6 +/- 2.0 vs. -6.7 +/- 2.0; p < 0.001) with significant improvements sustained to Week 12 (p = 0.019). Dysport also produced significant improvements in TWSTRS subscale scores, VAS pain scores, and subject/investigator's VAS symptom assessments compared to placebo. The mean duration of open-label study participation was 51.9 weeks (range 3.9-94.0 weeks). During open-label treatment, all treatment cycles resulted in improvements in mean TWSTRS total and subscale scores at Week 4 post-treatment; greatest improvement was seen in cycle 1. The mean duration between treatment cycles was 15-17 weeks. Dysport demonstrated a good long-term safety profile; most adverse events were mild or moderate and typical of the known safety profile of Dysport in this indication. These results confirm that Dysport (500 units) is safe, effective, and well-tolerated in patients with CD.
- Published
- 2009
35. Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease
- Author
-
A. Jon Stoessl, Dennis A. Turner, Gary Hotton, David J. Brooks, Elena Moro, John G. Nutt, Peter Heywood, Matthew Brodsky, Richard D. Penn, Mark Stacy, Andres M. Lozano, Robert J. Coffey, Steven S. Gill, Patrick J. Kelly, Burton L. Scott, Vijay Dhawan, James Matcham, Arif Dalvi, Kim J. Burchiel, W. J. Elias, Edward R. Laws, Anthony E. Lang, Michael Traub, Nik K. Patel, and V. G. Frederich Wooten
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Placebo ,Severity of Illness Index ,law.invention ,Drug Delivery Systems ,Randomized controlled trial ,Double-Blind Method ,Neurotrophic factors ,law ,Glial cell line-derived neurotrophic factor ,medicine ,Clinical endpoint ,Humans ,Glial Cell Line-Derived Neurotrophic Factor ,Cerebral dopamine neurotrophic factor ,Analysis of Variance ,biology ,Dose-Response Relationship, Drug ,Putamen ,Parkinson Disease ,Middle Aged ,Recombinant Proteins ,Surgery ,Dihydroxyphenylalanine ,Clinical trial ,Treatment Outcome ,Neurology ,Dyskinesia ,Anesthesia ,Positron-Emission Tomography ,biology.protein ,Drug Evaluation ,Female ,Neurology (clinical) ,medicine.symptom ,Psychology - Abstract
Objective Glial cell line–derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open-label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). Methods Thirty-four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15μg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and 18F-dopa uptake. Results At 6 months, mean percentage changes in “off” UPDRS motor score were −10.0% and −4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, −23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean 18F-dopa influx constant (p = 0.019) was observed. Serious, device-related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on-study and two in the open-label extension). Interpretation Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased 18F-dopa uptake. It is uncertain whether technical differences between this trial and positive open-label studies contributed in any way this negative outcome. Ann Neurol 2006
- Published
- 2006
36. Bilateral deep brain stimulation targeting ventralis intermedius nucleus to treat a professional musician's task-specific tremor
- Author
-
Matthew Brodsky, Nathaniel Whitney, Seth Kareus, Justin S. Cetas, and Kathryn A. Chung
- Subjects
medicine.medical_specialty ,Deep brain stimulation ,business.industry ,medicine.medical_treatment ,Audiology ,Task (project management) ,medicine.anatomical_structure ,Text mining ,Neurology ,medicine ,Neurology (clinical) ,Psychology ,business ,Neuroscience ,Nucleus - Published
- 2013
37. Repeated incobotulinumtoxinA injections with flexible dosing intervals in blepharospasm
- Author
-
Joseph Jankovic, S.K. Grafe, Daniel D. Truong, Matthew Brodsky, Hubert H. Fernandez, and V. G. H. Evidente
- Subjects
Flexible dosing ,business.industry ,Anesthesia ,Blepharospasm ,medicine ,medicine.symptom ,Toxicology ,business - Published
- 2013
38. Sleepiness in Parkinson's disease: a controlled study
- Author
-
C. Warren Olanow, Matthew Brodsky, Tom Roth, and James Godbold
- Subjects
Adult ,Male ,medicine.medical_specialty ,Levodopa ,Parkinson's disease ,Poison control ,Excessive daytime sleepiness ,Disorders of Excessive Somnolence ,Central nervous system disease ,Antiparkinson Agents ,Internal medicine ,Surveys and Questionnaires ,medicine ,Humans ,Aged ,Sleep Stages ,Analysis of Variance ,business.industry ,Epworth Sleepiness Scale ,Contraindications ,Parkinson Disease ,Middle Aged ,medicine.disease ,Neurology ,Physical therapy ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Somnolence ,medicine.drug - Abstract
Sudden-onset sleep episodes while driving have been reported in Parkinson's disease (PD) patients, and termed sleep attacks because they were reported to be irresistible and to occur without warning. We postulate that these episodes are due to excessive daytime sleepiness secondary to the high frequency of sleep disorders in PD patients and the sedative effects of dopaminergic medications. We assessed the frequency and relationship between excess daytime sleepiness and sleep episodes while driving (SE) in patients with PD. We evaluated 101 consecutive PD patients presenting to the Movement Disorder Center at the Mount Sinai School of Medicine using a questionnaire that incorporated a subjective estimate of sleepiness, the Epworth Sleepiness Scale (ESS) and information on disease severity and dopaminergic medications. One hundred age-matched respondents without PD served as a control population. Excess daytime sleepiness was reported in 76% of PD patients compared to 47% of controls (P0.05). The mean ESS scores for PD patients was 9.1 +/- 6.1 versus 5.7 +/- 4.4 in controls (P0.001). ESS scoresor =10 were observed in 40.6% of PD patients compared to 19% of controls (P0.01) and 24% of PD patients had scoresor =15, compared to 5% of controls (P0.001). Sleep episodes while driving were experienced by 20.8% of PD drivers compared to 6% of control drivers (P0.05). The mean daily levodopa (L-dopa) dose equivalent was 1,142 +/- 858 mg in PD drivers who experienced a SE while driving compared to 626 +/- 667 mg in those who had not (P0.05). Similarly, ESS was significantly greater in drivers with a SE than in those without (11.6 +/- 6.4 vs. 8.4 +/- 4.1; P0.05). Logistic regression analysis demonstrated that ESS and mean daily L-dopa dose equivalents were predictors of sleep episodes while driving, whereas age, gender, disease severity, and individual dopaminergic agents were not. These findings support the notion that sleep episodes while driving in PD patients are related to excess daytime sleepiness and dopaminergic load. Physicians should advise and treat patients accordingly.
- Published
- 2003
39. Neurologic drug-psychotropic drug update
- Author
-
Matthew Brodsky, Anwarul Karim, James J. Strain, Carol Himelein, R.Sandlin Lowe, and Gina Caliendo
- Subjects
Drug ,MedWatch ,medicine.medical_specialty ,Brain Diseases ,Psychotropic Drugs ,business.industry ,media_common.quotation_subject ,Mental Disorders ,MEDLINE ,Drug Synergism ,Carbamazepine ,Drug interaction ,Psychiatry and Mental health ,Psychotropic drug ,Mood ,mental disorders ,Medicine ,Humans ,Drug Interactions ,Formulary ,business ,Psychiatry ,medicine.drug ,media_common ,Central Nervous System Agents - Abstract
It is essential that both the neurologist and the psychiatrist be aware of the neurology drug-psychotropic drug interactions because neurologists prescribe many psychotropic medications and psychiatric consultants often recommend the use of psychotropic drugs for neurology patients. Six methods of examining drug-drug interactions were employed: 1) PubMed (MEDLINE); 2) Hanston's Drug Interaction Analysis and Management Text (July 2001 quarterly updated version); 3) Drug Interactions Facts (quarterly updated version through July 2001); 4) Micromedex Drug-dex ; 5) American Hospital Formulary Service Drug Information ; 6) Food and Drug Administration ( MedWatch ) Dear Doctor Letters and new labeling. Over eighty important interactions of significance level 1 (major), or significance level 2 (minor) were found. Furthermore, over one-third of the neurologist's most commonly administered medications were those also employed by the psychiatrist, but not necessarily for the same reason, e.g., carbamazepine, for seizure control (neurologist) or mood stabilization (psychiatrist).
- Published
- 2002
40. A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease
- Author
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Diane Cote, Jeri Sieren, Alex Rajput, James W. Tetrud, Paul J. Tuite, Christopher T. Ingvoldstad, Cheryl Waters, Shari Niswonger, Roger Kurlan, David D. Song, Jennifer Young, Samuel Markind, Alicia Palao, Munira Sultana, Christine Hunter, Karen Williams, Sandra K. Kostyk, John G. Nutt, Andrew Feigin, Dragos Mihaila, Karen Blindauer, Abraham Lieberman, Annette Robinson, Adrienna Winters, Michelle Cines, Mattson Ogg, Robert A. Hauser, Ira Shoulson, Julia Spears, Jorge L. Juncos, William G. Ondo, David Simon, Mark Stacy, Stacy Merritt, Barbara Shannon, Un Jung Kang, Katie Kompoliti, Cheryl Deeley, Joanne Field, Arthur Watts, Buff Farrow, Karen Helles, Katharine Smith, Karen Thomas, Rajan Prakash, Joel S. Perlmutter, Rajeev Kumar, Mandar Jog, Pamela King, Neal Hermanowicz, Stephen G. Reich, Mark Chilton, Lawrence Severt, Vanessa K. Hinson, Kapil D. Sethi, Mark F. Lew, Pinky Agarwal, Clifford M Shults, Natividad Stover, Richard H. Haas, Jayaraman Rao, Thomas Mayer, Thyagarajan Subramanian, Althea Silver, Richard M. Zweig, Lin Zhang, Hubert H. Fernandez, Linda Cole, Charles H. Adler, Jean Rivest, Marye Kellermann, Marlene Lind, Stephanie Wilson, Jennifer Conway, Ray L. Watts, Monica Beland, Joseph H. Friedman, Michael S. Okun, Maureen Cook, Stephen Grill, Cindy Zadikoff, Irene Litvan, Donna Stuppy Ford, Karen Frei, L Pepper Lumina, David Grimes, Sofya Glazman, Edward Drasby, Wendy R. Galpern, Susan Rolandelli, Sharon Evans, Bernard Ravina, Robert W. Hamill, Jo Bergholte, Andrew Siderowf, W.R. Wayne Martin, Rajesh Pahwa, Sanja Obradov, April Langhammer, Lorelei Derwent, Barbara Sommerfeld, M. Flint Beal, Alok Sahay, Anita Blenke, Liza Reys, Melisa Pelikan, Amy Duffy, Holly A. Shill, Eric Molho, Ivan Bodis-Wollner, Candace Cotto, Marilyn Cowper, Marian L. Evatt, Ani Arkun, Johanna M Hartlein, Nancy Zappala, Clara Schindler Propsom, Matthew Brodsky, Colette Lynn Hilliard, Stephanie Lessig, Stephanie Guthrie, Joanne Wojcieszek, Deborah Fontaine, Irene H. Richard, Zoltan Mari, Kathy Davis, Carlos Singer, Samuel A. Ellias, Lawrence Elmer, Julie So, Louisette Bond, Janis M. Miyasaki, Camille Swartz, Ranjit Ranawaya, Brian Griebner, Ramon L. Rodriguez, Ronald F. Pfeiffer, Becky Dunlop, David Oakes, Michel Panisset, Tiffini Voss, Joohi Jimenez-Shahed, Karyn Boyar, Cathi-Ann Thomas, Victoria Snively, Claire Henchcliffe, Margaret C. Lannon, Maureen Gartner, Cherissa Sia, Maureen A. Leehey, Joan Young, Anwar Ahmed, David S. Russell, Melissa J. Nirenberg, Emmanuelle Pourcher, James T. Boyd, Lauren Kraics, Ted M. Dawson, Ergun Y. Uc, Shan Gao, and Angel Figueroa
- Subjects
Male ,medicine.medical_specialty ,Ubiquinone ,Population ,Unified Parkinson's disease rating scale ,Placebo ,Antioxidants ,law.invention ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Prospective Studies ,education ,Adverse effect ,Prospective cohort study ,Aged ,education.field_of_study ,Dose-Response Relationship, Drug ,business.industry ,Parkinsonism ,Parkinson Disease ,Middle Aged ,medicine.disease ,Clinical trial ,Early Diagnosis ,Treatment Outcome ,Physical therapy ,Female ,Neurology (clinical) ,business - Abstract
Importance Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. Objective To examine whether CoQ10 could slow disease progression in early PD. Design, Setting, and Participants A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson’s Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. Interventions The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. Main Outcomes and Measures Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. Results The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo). Conclusions and Relevance Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit. Trial Registration clinicaltrials.gov Identifier:NCT00740714
- Published
- 2014
41. Long-term treatment of blepharospasm and cervical dystonia: Incobotulinum /INS;toxin /INS;A is well tolerated when injected at flexible intervals based on patient needs
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Cynthia L. Comella, Matthew Brodsky, Daniel Truong, Angelika Hanschmann, Joseph Jankovic, Hubert H. Fernandez, and Virgilio Gerald H. Evidente
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medicine.medical_specialty ,Long term treatment ,Toxin ,business.industry ,Blepharospasm ,medicine.disease ,medicine.disease_cause ,Surgery ,Neurology ,Anesthesia ,medicine ,Neurology (clinical) ,Cervical dystonia ,medicine.symptom ,business - Published
- 2013
42. Initial pharmacotherapy in a population of veterans with Parkinson disease
- Author
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Kari Swarztrauber, Caroline Koudelka, and Matthew Brodsky
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Male ,Pediatrics ,Databases, Factual ,Disease ,Cholinergic Antagonists ,Antiparkinson Agents ,Levodopa ,Pharmacy records ,Degenerative disease ,Psychology ,Practice Patterns, Physicians' ,Veterans ,Aged, 80 and over ,Psychiatry ,education.field_of_study ,Age Factors ,Parkinson Disease ,Middle Aged ,United States Department of Veterans Affairs ,Neurology ,Dopamine Agonists ,Medicine ,Specialization ,medicine.drug ,medicine.medical_specialty ,Northwestern United States ,Population ,Specialty ,Drug Prescriptions ,Central nervous system disease ,Pharmacotherapy ,Dopamine ,Selegiline ,Amantadine ,medicine ,Humans ,music ,education ,Aged ,Retrospective Studies ,Primary Health Care ,business.industry ,music.record_label ,medicine.disease ,Drug Utilization ,United States ,Geriatrics ,Physical therapy ,Dementia ,Neurology (clinical) ,business - Abstract
The authors analyzed patient and prescribing provider characteristics for 530 veterans identified from VA pharmacy records with Parkinson disease (PD) and initial pharmacotherapy. Neurologists prescribed 29% of initial therapy. While a patient being younger and seeing a movement disorder specialist predicted receiving dopamine agonists, only 20% of patients younger than age 65 years received dopamine agonists. Initial pharmacotherapy is strongly influenced by the provider's specialty but mostly initiated by providers without PD expertise.
- Published
- 2006
43. IncobotulinumtoxinA (Xeomin(R)) Is Well Tolerated for the Treatment of Blepharospasm When Injected According to Patient Needs (PD4.010)
- Author
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Stephen Gollomp, Matthew Brodsky, V. G. H. Evidente, Angelika Hanschmann, M. Marx, and Joseph Jankovic
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business.industry ,Anesthesia ,Blepharospasm ,Medicine ,Neurology (clinical) ,medicine.symptom ,business - Published
- 2012
44. Correction
- Author
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A. Jon Stoessl, Peter Heywood, Richard D. Penn, Vijay Dhawan, James Matcham, Nik K. Patel, Michael Traub, Matthew Brodsky, W. J. Elias, Patrick J. Kelly, Burton L. Scott, Robert J. Coffey, Andres M. Lozano, Dennis A. Turner, Kim J. Burchiel, John G. Nutt, Edward R. Laws, Anthony E. Lang, V. G. Frederich Wooten, Mark Stacy, Steven S. Gill, David J. Brooks, Elena Moro, Arif Dalvi, and Gary Hotton
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Oncology ,medicine.medical_specialty ,Neurology ,biology ,business.industry ,Disease ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,Glial cell line-derived neurotrophic factor ,biology.protein ,Medicine ,Neurology (clinical) ,business ,Neuroscience - Published
- 2006
45. Dynamics of Retrieval Strategies for Remote Memories
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Charu Ramakrishnan, Inbal Goshen, Karl Deisseroth, Jenelle Wallace, Rohit Prakash, Viviana Gradinaru, and Matthew Brodsky
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Neurons ,Neocortex ,Memory, Long-Term ,Recall ,Biochemistry, Genetics and Molecular Biology(all) ,Hippocampus ,Fear ,Optogenetics ,Hippocampal formation ,Biology ,Gyrus Cinguli ,General Biochemistry, Genetics and Molecular Biology ,Mice, Inbred C57BL ,Mice ,medicine.anatomical_structure ,nervous system ,medicine ,Excitatory postsynaptic potential ,Animals ,Humans ,Memory consolidation ,Neuroscience ,Anterior cingulate cortex - Abstract
SummaryPrevailing theory suggests that long-term memories are encoded via a two-phase process requiring early involvement of the hippocampus followed by the neocortex. Contextual fear memories in rodents rely on the hippocampus immediately following training but are unaffected by hippocampal lesions or pharmacological inhibition weeks later. With fast optogenetic methods, we examine the real-time contribution of hippocampal CA1 excitatory neurons to remote memory and find that contextual fear memory recall, even weeks after training, can be reversibly abolished by temporally precise optogenetic inhibition of CA1. When this inhibition is extended to match the typical time course of pharmacological inhibition, remote hippocampus dependence converts to hippocampus independence, suggesting that long-term memory retrieval normally depends on the hippocampus but can adaptively shift to alternate structures. Further revealing the plasticity of mechanisms required for memory recall, we confirm the remote-timescale importance of the anterior cingulate cortex (ACC) and implicate CA1 in ACC recruitment for remote recall.
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46. Directional Versus Nondirectional DBS for ET
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Matthew Brodsky, Associate Professor of Neurology
- Published
- 2021
47. Clinical Outcomes of Deep Brain Stimulator (DBS) Electrodes Placed Using Intraoperative Computed Tomography (CT) and Frameless Stereotaxis
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Matthew Brodsky, Principal Investigator
- Published
- 2019
48. Ultra High Field Magnetic Resonance Imaging as a Biomarker for Premotor Parkinson's Disease
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Matthew Brodsky, Associate Professor of Neurology
- Published
- 2019
49. Effects of a Dopamine Agonist on Pharmacodynamics of Levodopa in Parkinson's Disease (DALI)
- Author
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Boehringer Ingelheim and Matthew Brodsky M.D.
- Published
- 2008
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