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1. Prognostic relevance of gait-related cognitive functions for dementia conversion in amnestic mild cognitive impairment

Author

Tuena, Cosimo, Maestri, Sara, Serino, Silvia, Pedroli, Elisa, Stramba-Badiale, Marco, Riva, Giuseppe, Silbert, Lisa C., Lind, Betty, Crissey, Rachel, Kaye, Jeffrey A., Carter, Raina, Dolen, Sara, Quinn, Joseph, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Dagerman, Karen, Spann, Bryan M., Brewer, Jame, Fleisher, Adam, Vanderswag, Helen, Ziolkowski, Jaimie, Heidebrink, Judith L., Zbizek-Nulph, Lisa, Lord, Joanne L., Albers, Colleen S., Petersen, Ronald, Mason, Sara S., Knopman, David, Johnson, Kri, Villanueva-Meyer, Javier, Pavlik, Valory, Pacini, Nathaniel, Lamb, Ashley, Kass, Joseph S., Doody, Rachelle S., Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Mintz, Akiva, Ances, Beau, Morris, John C., Winkfield, David, Carroll, Maria, Stobbs-Cucchi, Georgia, Oliver, Angela, Creech, Mary L., Mintun, Mark A., Schneider, Stacy, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Marson, Daniel, Grossman, Hillel, Goldstein, Martin A., Greenberg, Jonathan, Mitsis, Effie, Shah, Raj C., Lamar, Melissa, Samuels, Patricia, Duara, Ranjan, Greig-Custo, Maria T., Rodriguez, Rosemarie, Albert, Marilyn, Onyike, Chiadi, Farrington, Leonie, Rudow, Scott, Brichko, Rottislav, Kielb, Stephanie, Smith, Amanda, Raj, Balebail Ashok, Fargher, Kristin, Sadowski, Martin, Wisniewski, Thoma, Shulman, Melanie, Faustin, Arline, Rao, Julia, Castro, Karen M., Ulysse, Anaztasia, Chen, Shannon, Doraiswamy, P. Murali, Petrella, Jeffrey R., James, Olga, Wong, Terence Z., Borges-Neto, Salvador, Karlawish, Jason H., Wolk, David A., Vaishnavi, Sanjeev, Clark, Christopher M., Arnold, Steven E., Smith, Charles D., Jicha, Gregory A., Khouli, Riham El, Raslau, Flavius D., Lopez, Oscar L., Oakley, Maryann, Simpson, Donna M., Porsteinsson, Anton P., Martin, Kim, Kowalski, Nancy, Keltz, Melanie, Goldstein, Bonnie S., Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Thai, Gaby, Pierce, Aimee, Yanez, Beatriz, Sosa, Elizabeth, Witbracht, Megan, Kelley, Brendan, Nguyen, Trung, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Hajjar, Ihab, Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Silverman, Daniel H. S., Kremen, Sarah, Apostolova, Liana, Tingus, Kathleen, Lu, Po H., Bartzokis, George, Woo, Ellen, Teng, Edmond, Graff-Radford, Neill R., Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van Dyck, Christopher H., Mecca, Adam P., Good, Susan P., Macavoy, Martha G., Carson, Richard E., Varma, Pradeep, Chertkow, Howard, Vaitekunas, Susan, Hosein, Chri, Black, Sandra, Stefanovic, Bojana, Heyn, Chri, Hsiung, Ging-Yuek Robin, Kim, Ellen, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Kertesz, Andrew, Drost, Dick, Rogers, John, Grant, Ian, Muse, Brittanie, Rogalski, Emily, Robson, Jordan, Mesulam, M. -Marsel, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Rosen, Howard J., Miller, Bruce L., Weiner, Micheal W., Perry, David, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Mccann, Kelly, Poe, Jessica, Marshall, Gad A., Sperling, Reisa A., Johnson, Keith A., Yesavage, Jerome, Taylor, Joy L., Chao, Steven, Coleman, Jaila, White, Jessica D., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Belden, Christine M., Atri, Alireza, Clark, Kelly A., Zamrini, Edward, Sabbagh, Marwan, Killiany, Ronald, Stern, Robert, Mez, Jesse, Kowall, Neil, Budson, Andrew E., Obisesan, Thomas O., Ntekim, Oyonumo E., Wolday, Saba, Khan, Javed I., Nwulia, Evaristu, Nadarajah, Sheeba, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curti, Fatica, Parianne, Fletcher, Evan, Maillard, Pauline, Olichney, John, Decarli, Charle, Carmichael, Owen, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Borrie, Michael, Lee, T. -Y., Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Perrin, Allison, Burke, Anna, Scharre, Douglas W., Kataki, Maria, Tarawneh, Rawan, Hart, David, Zimmerman, Earl A., Celmins, Dzintra, Miller, Delwyn D., Ponto, Laura L. Bole, Smith, Karen Ekstam, Koleva, Hristina, Shim, Hyungsub, Nam, Ki Won, Schultz, Susan K., Williamson, Jeff D., Craft, Suzanne, Cleveland, Jo, Yang, Mia, Sink, Kaycee M., Ott, Brian R., Drake, Jonathan, Tremont, Geoffrey, Daiello, Lori A., Drake, Jonathan D., Ritter, Aaron, Bernick, Charle, Munic, Donna, O’Connelll, Abigail, Mintzer, Jacobo, Wiliams, Arthur, Masdeu, Joseph, Shi, Jiong, Garcia, Angelica, Newhouse, Paul, Potkin, Steven, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Kittur, Smita, Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Relkin, Norman, Chiang, Gloria, Lee, Athena, Lin, Michael, Ravdin, Lisa, Null, Null, Serino, Silvia (ORCID:0000-0002-8422-1358), Riva, Giuseppe (ORCID:0000-0003-3657-106X), Tuena, Cosimo, Maestri, Sara, Serino, Silvia, Pedroli, Elisa, Stramba-Badiale, Marco, Riva, Giuseppe, Silbert, Lisa C., Lind, Betty, Crissey, Rachel, Kaye, Jeffrey A., Carter, Raina, Dolen, Sara, Quinn, Joseph, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Dagerman, Karen, Spann, Bryan M., Brewer, Jame, Fleisher, Adam, Vanderswag, Helen, Ziolkowski, Jaimie, Heidebrink, Judith L., Zbizek-Nulph, Lisa, Lord, Joanne L., Albers, Colleen S., Petersen, Ronald, Mason, Sara S., Knopman, David, Johnson, Kri, Villanueva-Meyer, Javier, Pavlik, Valory, Pacini, Nathaniel, Lamb, Ashley, Kass, Joseph S., Doody, Rachelle S., Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Mintz, Akiva, Ances, Beau, Morris, John C., Winkfield, David, Carroll, Maria, Stobbs-Cucchi, Georgia, Oliver, Angela, Creech, Mary L., Mintun, Mark A., Schneider, Stacy, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Marson, Daniel, Grossman, Hillel, Goldstein, Martin A., Greenberg, Jonathan, Mitsis, Effie, Shah, Raj C., Lamar, Melissa, Samuels, Patricia, Duara, Ranjan, Greig-Custo, Maria T., Rodriguez, Rosemarie, Albert, Marilyn, Onyike, Chiadi, Farrington, Leonie, Rudow, Scott, Brichko, Rottislav, Kielb, Stephanie, Smith, Amanda, Raj, Balebail Ashok, Fargher, Kristin, Sadowski, Martin, Wisniewski, Thoma, Shulman, Melanie, Faustin, Arline, Rao, Julia, Castro, Karen M., Ulysse, Anaztasia, Chen, Shannon, Doraiswamy, P. Murali, Petrella, Jeffrey R., James, Olga, Wong, Terence Z., Borges-Neto, Salvador, Karlawish, Jason H., Wolk, David A., Vaishnavi, Sanjeev, Clark, Christopher M., Arnold, Steven E., Smith, Charles D., Jicha, Gregory A., Khouli, Riham El, Raslau, Flavius D., Lopez, Oscar L., Oakley, Maryann, Simpson, Donna M., Porsteinsson, Anton P., Martin, Kim, Kowalski, Nancy, Keltz, Melanie, Goldstein, Bonnie S., Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Thai, Gaby, Pierce, Aimee, Yanez, Beatriz, Sosa, Elizabeth, Witbracht, Megan, Kelley, Brendan, Nguyen, Trung, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Hajjar, Ihab, Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Silverman, Daniel H. S., Kremen, Sarah, Apostolova, Liana, Tingus, Kathleen, Lu, Po H., Bartzokis, George, Woo, Ellen, Teng, Edmond, Graff-Radford, Neill R., Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van Dyck, Christopher H., Mecca, Adam P., Good, Susan P., Macavoy, Martha G., Carson, Richard E., Varma, Pradeep, Chertkow, Howard, Vaitekunas, Susan, Hosein, Chri, Black, Sandra, Stefanovic, Bojana, Heyn, Chri, Hsiung, Ging-Yuek Robin, Kim, Ellen, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Kertesz, Andrew, Drost, Dick, Rogers, John, Grant, Ian, Muse, Brittanie, Rogalski, Emily, Robson, Jordan, Mesulam, M. -Marsel, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Rosen, Howard J., Miller, Bruce L., Weiner, Micheal W., Perry, David, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Mccann, Kelly, Poe, Jessica, Marshall, Gad A., Sperling, Reisa A., Johnson, Keith A., Yesavage, Jerome, Taylor, Joy L., Chao, Steven, Coleman, Jaila, White, Jessica D., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Belden, Christine M., Atri, Alireza, Clark, Kelly A., Zamrini, Edward, Sabbagh, Marwan, Killiany, Ronald, Stern, Robert, Mez, Jesse, Kowall, Neil, Budson, Andrew E., Obisesan, Thomas O., Ntekim, Oyonumo E., Wolday, Saba, Khan, Javed I., Nwulia, Evaristu, Nadarajah, Sheeba, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curti, Fatica, Parianne, Fletcher, Evan, Maillard, Pauline, Olichney, John, Decarli, Charle, Carmichael, Owen, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Borrie, Michael, Lee, T. -Y., Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Perrin, Allison, Burke, Anna, Scharre, Douglas W., Kataki, Maria, Tarawneh, Rawan, Hart, David, Zimmerman, Earl A., Celmins, Dzintra, Miller, Delwyn D., Ponto, Laura L. Bole, Smith, Karen Ekstam, Koleva, Hristina, Shim, Hyungsub, Nam, Ki Won, Schultz, Susan K., Williamson, Jeff D., Craft, Suzanne, Cleveland, Jo, Yang, Mia, Sink, Kaycee M., Ott, Brian R., Drake, Jonathan, Tremont, Geoffrey, Daiello, Lori A., Drake, Jonathan D., Ritter, Aaron, Bernick, Charle, Munic, Donna, O’Connelll, Abigail, Mintzer, Jacobo, Wiliams, Arthur, Masdeu, Joseph, Shi, Jiong, Garcia, Angelica, Newhouse, Paul, Potkin, Steven, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Kittur, Smita, Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Relkin, Norman, Chiang, Gloria, Lee, Athena, Lin, Michael, Ravdin, Lisa, Null, Null, Serino, Silvia (ORCID:0000-0002-8422-1358), and Riva, Giuseppe (ORCID:0000-0003-3657-106X)

Abstract

BackgroundIncreasing research suggests that gait abnormalities can be a risk factor for Alzheimer's Disease (AD). Notably, there is growing evidence highlighting this risk factor in individuals with amnestic Mild Cognitive Impairment (aMCI), however further studies are needed. The aim of this study is to analyze cognitive tests results and brain-related measures over time in aMCI and examine how the presence of gait abnormalities (neurological or orthopedic) or normal gait affects these trends. Additionally, we sought to assess the significance of gait and gait-related measures as prognostic indicators for the progression from aMCI to AD dementia, comparing those who converted to AD with those who remained with a stable aMCI diagnosis during the follow-up.MethodsFour hundred two individuals with aMCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. Robust linear mixed-effects models were used to study the impact of gait abnormalities on a comprehensive neuropsychological battery over 36 months while controlling for relevant medical variables at baseline. The impact of gait on brain measures was also investigated. Lastly, the Cox proportional-hazards model was used to explore the prognostic relevance of abnormal gait and neuropsychological associated tests.ResultsWhile controlling for relevant covariates, we found that gait abnormalities led to a greater decline over time in attention (DSST) and global cognition (MMSE). Intriguingly, psychomotor speed (TMT-A) and divided attention (TMT-B) declined uniquely in the abnormal gait group. Conversely, specific AD global cognition tests (ADAS-13) and auditory-verbal memory (RAVLT immediate recall) declined over time independently of gait profile. All the other cognitive tests were not significantly affected by time or by gait profile. In addition, we found that ventricles size increased faster in the abnormal gait group compared to the normal gait group. In terms of prognosis, abnormal gai

Published
2023

3. Hypothalamic deep brain stimulation augments walking after spinal cord injury.

Author

Cho N, Squair JW, Aureli V, James ND, Bole-Feysot L, Dewany I, Hankov N, Baud L, Leonhartsberger A, Sveistyte K, Skinnider MA, Gautier M, Laskaratos A, Galan K, Goubran M, Ravier J, Merlos F, Batti L, Pages S, Berard N, Intering N, Varescon C, Watrin A, Duguet L, Carda S, Bartholdi KA, Hutson TH, Kathe C, Hodara M, Anderson MA, Draganski B, Demesmaeker R, Asboth L, Barraud Q, Bloch J, and Courtine G

Subjects
Animals, Humans, Rats, Mice, Female, Recovery of Function, Male, Spinal Cord physiopathology, Spinal Cord metabolism, Hypothalamus metabolism, Hypothalamic Area, Lateral physiopathology, Pilot Projects, Adult, Middle Aged, Spinal Cord Injuries therapy, Spinal Cord Injuries physiopathology, Deep Brain Stimulation methods, Walking, Neurons metabolism
Abstract

A spinal cord injury (SCI) disrupts the neuronal projections from the brain to the region of the spinal cord that produces walking, leading to various degrees of paralysis. Here, we aimed to identify brain regions that steer the recovery of walking after incomplete SCI and that could be targeted to augment this recovery. To uncover these regions, we constructed a space-time brain-wide atlas of transcriptionally active and spinal cord-projecting neurons underlying the recovery of walking after incomplete SCI. Unexpectedly, interrogation of this atlas nominated the lateral hypothalamus (LH). We demonstrate that glutamatergic neurons located in the LH (LH Vglut2 ) contribute to the recovery of walking after incomplete SCI and that augmenting their activity improves walking. We translated this discovery into a deep brain stimulation therapy of the LH (DBS LH ) that immediately augmented walking in mice and rats with SCI and durably increased recovery through the reorganization of residual lumbar-terminating projections from brainstem neurons. A pilot clinical study showed that DBS LH immediately improved walking in two participants with incomplete SCI and, in conjunction with rehabilitation, mediated functional recovery that persisted when DBS LH was turned off. There were no serious adverse events related to DBS LH . These results highlight the potential of targeting specific brain regions to maximize the engagement of spinal cord-projecting neurons in the recovery of neurological functions after SCI. Further trials must establish the safety and efficacy profile of DBS LH , including potential changes in body weight, psychological status, hormonal profiles and autonomic functions., Competing Interests: Competing interests: G.C., J.B., N.C., J.W.S., R.D., L.A. and L.B.-F. hold various patents in relation to the present work. G.C. is a consultant of ONWARD Medical. G.C. and J.B. are minority shareholders of ONWARD Medical, a company with partial relationships with the presented work. The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Published
2024
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4. Canadian Spine Society: 24th Annual Scientific Conference, Wednesday, February 28 - Saturday, March 2, Fairmont Chateau Whistler, Whistler, B.C., Canada.

Author

Dionne A, Al-Zakri M, Labelle H, Joncas J, Parent S, Mac-Thiong JM, Miyanji F, Lonner B, Eren A, Cahill P, Parent S, Newton P, Dermott JA, Jaakkimainen L, To T, Bouchard M, Howard A, Lebel DE, Hardy S, Malhotra AK, Dermott J, Thevarajah D, Mathias KDA, Yoon S, Sakhrekar R, Lebel DE, Kim DJ, Hadi A, Doria A, Mitani A, Dermott J, Howard A, Lebel D, Yoon S, Mathias K, Dermott J, Lebel D, Miyanji F, Newton P, Lonner B, Bastrom T, Samdani A, Roy-Beaudry M, Beauséjour M, Imbeault R, Dufresne J, Parent S, Romeo J, Livock H, Smit K, Jarvis J, Tice A, Chan VK, Cho R, Poon S, Skaggs DL, Shumilak GK, Rocos B, Sardi JP, Charalampidis A, Gum J, Lewis SJ, Tretiakov PS, Onafowokan O, Mir J, Das A, Williamson T, Dave P, Imbo B, Lebovic J, Jankowski P, Passias PG, Lewis S, Aljamaan Y, Lenke LG, Smith J, Varshney VP, Sahjpaul R, Paquette S, Osborn J, Pelletier-Roy R, Asmussen M, Birk M, Ludwig T, Nicholls F, Zohar A, Loomans J, Pellise F, Smith JS, Kato S, Sardar Z, Lenke L, Lewis SJ, Abbas A, Toor J, Sahi G, Kovacevic D, Lex J, Miyanji F, Rampersaud R, Perruccio AV, Mahomed N, Canizares M, Rizkallah M, Lebreton MA, Boubez G, Shen J, AlShakfa F, Kamel Y, Osman G, Wang Z, Koegl N, Herrington B, Fernandes RR, Urquhart JC, Rampersaud YR, Bailey CS, Hakimjavadi R, Zhang T, DeVries Z, Wai EK, Kingwell SP, Stratton A, Tsai E, Wang Z, Phan P, Rampersaud R, Fine N, Stone L, Kapoor M, Chênevert A, Bédard S, McIntosh G, Goulet J, Couture J, Investigators C, LaRue B, Rosenstein B, Rye M, Roussac A, Naghdi N, Macedo LG, Elliott J, DeMont R, Weber MH, Pepin V, Dover G, Fortin M, Wang Z, Rizkallah M, Shen J, Lebreton MA, Florial E, AlShakfa F, Boubez G, Raj A, Amin P, McIntosh G, Rampersaud YR, AlDuwaisan AASM, Hakimjavadi R, Zhang T, Phan K, Stratton A, Tsai E, Kingwell S, Wai E, Phan P, Hebert J, Nowell S, Wedderkopp N, Vandewint A, Manson N, Abraham E, Small C, Attabib N, Bigney E, Koegl N, Craig M, Al-Shawwa A, Ost K, Tripathy S, Evaniew N, Jacobs B, Cadotte D, Malhotra AK, Evaniew N, Dea N, Investigators C, McIntosh G, Wilson JR, Evaniew N, Bailey CS, Rampersaud YR, Jacobs WB, Phan PP, Nataraj A, Cadotte DW, Weber MH, Thomas KC, Manson N, Attabib N, Paquet J, Christie SD, Wilson JR, Hall H, Fisher CG, McIntosh G, Dea N, Liu EY, Persad ARL, Baron N, Fourney D, Shakil H, Investigators C, Evaniew N, Wilson JR, Dea N, Phan P, Huang J, Fallah N, Dandurand C, Alfawaz T, Zhang T, Stratton A, Tsai E, Wai E, Kingwell S, Wang Z, Phan P, Investigators C, Zaldivar-Jolissaint JF, Charest-Morin R, McIntosh G, Fehlings MG, Pedro KM, Alvi MA, Wang JCW, Charest-Morin R, Dea N, Fisher C, Dvorak M, Kwon B, Ailon T, Paquette S, Street J, Dandurand C, Mumtaz R, Skaik K, Wai EK, Kingwell S, Stratton A, Tsai E, Phan PTN, Wang Z, Investigators C, Manoharan R, McIntosh G, Rampersaud YR, Smith-Forrester J, Douglas JE, Nemeth E, Alant J, Barry S, Glennie A, Oxner W, Weise L, Christie S, Liu EY, Persad ARL, Saeed S, Toyota P, Su J, Newton B, Coote N, Fourney D, Rachevits MS, Razmjou H, Robarts S, Yee A, Finkelstein J, Almojuela A, Zeiler F, Logsetty S, Dhaliwal P, Abdelnour M, Zhang Y, Wai E, Kingwell SP, Stratton A, Tsai E, Phan PT, Investigators C, Smith TA, Small C, Bigney E, Richardson E, Kearney J, Manson N, Abraham E, Attabib N, Bond M, Dombrowski S, Price G, García-Moreno JM, Hebert J, Qiu S, Surendran V, Cheung VSE, Ngana S, Qureshi MA, Sharma SV, Pahuta M, Guha D, Essa A, Shakil H, Malhotra A, Byrne J, Badhiwala J, Yuan E, He Y, Jack A, Mathieu F, Wilson JR, Witiw CD, Shakil H, Malhotra AK, Yuan E, Smith CW, Harrington EM, Jaffe RH, Wang AP, Ladha K, Nathens AB, Wilson JR, Witiw CD, Sandarage RV, Galuta A, Tsai EC, Rotem-Kohavi N, Dvorak MF, Xu J, Fallah N, Waheed Z, Chen M, Dea N, Evaniew N, Noonan V, Kwon B, Kwon BK, Malomo T, Charest-Morin R, Paquette S, Ailon T, Dandurand C, Street J, Fisher CG, Dea N, Heran M, Dvorak M, Jaffe R, Coyte P, Chan B, Malhotra A, Hancock-Howard R, Wilson J, Witiw C, Cho N, Squair J, Aureli V, James N, Bole-Feysot L, Dewany I, Hankov N, Baud L, Leonhartsberger A, Sveistyte K, Skinnider M, Gautier M, Galan K, Goubran M, Ravier J, Merlos F, Batti L, Pagès S, Bérard N, Intering N, Varescon C, Carda S, Bartholdi K, Hutson T, Kathe C, Hodara M, Anderson M, Draganski B, Demesmaeker R, Asboth L, Barraud Q, Bloch J, Courtine G, Christie SD, Greene R, Nadi M, Alant J, Barry S, Glennie A, Oxner B, Weise L, Julien L, Lownie C, Dvorak MF, Öner CFC, Dandurand C, Joeris A, Schnake K, Phillips M, Vaccaro AR, Bransford R, Popescu EC, El-Sharkawi M, Rajasekaran S, Benneker LM, Schroeder GD, Tee JW, France J, Paquet J, Allen R, Lavelle WF, Vialle E, Dea N, Dionne A, Magnuson D, Richard-Denis A, Petit Y, Bernard F, Barthélémy D, Mac-Thiong JM, Grassner L, Garcia-Ovejero D, Beyerer E, Mach O, Leister I, Maier D, Aigner L, Arevalo-Martin A, MacLean MA, Charles A, Georgiopoulos M, Charest-Morin R, Goodwin R, Weber M, Brouillard E, Richard-Denis A, Dionne A, Laassassy I, Khoueir P, Bourassa-Moreau É, Maurais G, Mac-Thiong JM, Zaldivar-Jolissaint JF, Dea N, Brown AA, So K, Manouchehri N, Webster M, Ethridge J, Warner A, Billingsley A, Newsome R, Bale K, Yung A, Seneviratne M, Cheng J, Wang J, Basnayake S, Streijger F, Heran M, Kozlowski P, Kwon BK, Golan JD, Elkaim LM, Alrashidi Q, Georgiopoulos M, Lasry OJ, Bednar DA, Love A, Nedaie S, Gandhi P, Amin PC, Raj A, McIntosh G, Neilsen CJ, Swamy G, Rampersaud R (On behalf of CSORN investigators), Vandewint A, Rampersaud YR, Hebert J, Bigney E, Manson N, Attabib N, Small C, Richardson E, Kearney J, Abraham E, Rampersaud R, Raj A, Marathe N, McIntosh G, Dhiman M, Bader TJ, Hart D, Swamy G, Duncan N, Dhiman M, Bader TJ, Ponjevic D, Matyas JR, Hart D, Swamy G, Duncan N, O'Brien CP, Hebert J, Bigney E, Kearney J, Richardson E, Abraham E, Manson N, Attabib N, Small C, LaRochelle L, Rivas G, Lawrence J, Ravinsky R, Kim D, Dermott J, Mitani A, Doria A, Howard A, Lebel D, Dermott JA, Switzer LS, Kim DJ, Lebel DE, Montpetit C, Vaillancourt N, Rosenstein B, Fortin M, Nadler E, Dermott J, Kim D, Lebel DE, Wolfe D, Rosenstein B, Fortin M, Wolfe D, Dover G, Boily M, Fortin M, Shakil H, Malhotra AK, Badhiwala JH, Karthikeyan V, He Y, Fehlings MG, Sahgal A, Dea N, Kiss A, Witiw CD, Redelmeier DR, Wilson JR, Caceres MP, Freire V, Shen J, Al-Shakfa F, Ahmed O, Wang Z, Kwan WC, Zuckerman SL, Fisher CG, Laufer I, Chou D, O'Toole JE, Schultheiss M, Weber MH, Sciubba DM, Pahuta M, Shin JH, Fehlings MG, Versteeg A, Goodwin ML, Boriani S, Bettegowda C, Lazary A, Gasbarrini A, Reynolds JJ, Verlaan JJ, Sahgal A, Gokaslan ZL, Rhines LD, Dea N, Truong VT, Dang TK, Osman G, Al-Shakfa F, Boule D, Shen J, Wang Z, Rizkallah M, Boubez G, Shen J, Phan P, Alshakfa F, Boule D, Belguendouz C, Kafi R, Yuh SJ, Shedid D, Wang Z, Wang Z, Shen J, Boubez G, Alshakfa F, Boulé D, Belguendouz C, Kafi R, Phan P, Shedid D, Yuh SJ, Rizkallah M, Silva YGMD, Weber L, Leão F, Essa A, Malhotra AK, Shakil H, Byrne J, Badhiwala J, Nathens AB, Azad TD, Yuan E, He Y, Jack AS, Mathieu F, Wilson JR, Witiw CD, Craig M, Guenther N, Valosek J, Bouthillier M, Enamundram NK, Rotem-Kohavi N, Humphreys S, Christie S, Fehlings M, Kwon B, Mac-Thiong JM, Phan P, Paquet J, Guay-Paquet M, Cohen-Adad J, Cadotte D, Dionne A, Mac-Thiong JM, Hong H, Kurban D, Xu J, Barthélémy D, Christie S, Fourney D, Linassi G, Sanchez AL, Paquet J, Sreenivasan V, Townson A, Tsai EC, Richard-Denis A, Kwan WC, Laghaei P, Kahlon H, Ailon T, Charest-Morin R, Dandurand C, Paquette S, Dea N, Street J, Fisher CG, Dvorak MF, Kwon BK, Thibault J, Dionne A, Al-Sofyani M, Pelletier-Roy R, Richard-Denis A, Bourassa-Moreau É, Mac-Thiong JM, Bouthillier M, Valošek J, Enamundram NK, Guay-Paquet M, Guenther N, Rotem-Kohavi N, Humphreys S, Christie S, Fehlings M, Kwon BK, Mac-Thiong JM, Phan P, Cadotte D, Cohen-Adad J, Reda L, Kennedy C, Stefaniuk S, Eftekhar P, Robinson L, Craven C, Dengler J, Kennedy C, Reda L, Stefaniuk S, Eftekhar P, Robinson L, Craven C, Dengler J, Roukerd MR, Patel M, Tsai E, Galuta A, Jagadeesan S, 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Published
2024
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5. Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis.

Author

Rowald A, Komi S, Demesmaeker R, Baaklini E, Hernandez-Charpak SD, Paoles E, Montanaro H, Cassara A, Becce F, Lloyd B, Newton T, Ravier J, Kinany N, D'Ercole M, Paley A, Hankov N, Varescon C, McCracken L, Vat M, Caban M, Watrin A, Jacquet C, Bole-Feysot L, Harte C, Lorach H, Galvez A, Tschopp M, Herrmann N, Wacker M, Geernaert L, Fodor I, Radevich V, Van Den Keybus K, Eberle G, Pralong E, Roulet M, Ledoux JB, Fornari E, Mandija S, Mattera L, Martuzzi R, Nazarian B, Benkler S, Callegari S, Greiner N, Fuhrer B, Froeling M, Buse N, Denison T, Buschman R, Wende C, Ganty D, Bakker J, Delattre V, Lambert H, Minassian K, van den Berg CAT, Kavounoudias A, Micera S, Van De Ville D, Barraud Q, Kurt E, Kuster N, Neufeld E, Capogrosso M, Asboth L, Wagner FB, Bloch J, and Courtine G

Subjects
Humans, Leg, Paralysis rehabilitation, Spinal Cord physiology, Walking physiology, Spinal Cord Injuries rehabilitation, Spinal Cord Stimulation
Abstract

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Published
2022
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