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1. 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, S.D., 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, Cathal, Lorach, H., Galvez, A., Tschopp, M., Herrmann, N., Wacker, M., Geernaert, L., Fodor, I., Radevich, V., Keybus, K. Van Den, Eberle, G., Pralong, E., Roulet, M., Ledoux, J.B., 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, Jurriaan, Delattre, V., Lambert, H., Minassian, K., Berg, C.A.T. van den, Kavounoudias, A., Micera, S., Ville, D. Van De, Barraud, Q., Kurt, E., Kuster, N., Neufeld, E., Capogrosso, M., Asboth, L., Wagner, F.B., Bloch, J., Courtine, G., Rowald, A., Komi, S., Demesmaeker, R., Baaklini, E., Hernandez-Charpak, S.D., 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, Cathal, Lorach, H., Galvez, A., Tschopp, M., Herrmann, N., Wacker, M., Geernaert, L., Fodor, I., Radevich, V., Keybus, K. Van Den, Eberle, G., Pralong, E., Roulet, M., Ledoux, J.B., 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, Jurriaan, Delattre, V., Lambert, H., Minassian, K., Berg, C.A.T. van den, Kavounoudias, A., Micera, S., Ville, D. Van De, Barraud, Q., Kurt, E., Kuster, N., Neufeld, E., Capogrosso, M., Asboth, L., Wagner, F.B., Bloch, J., and Courtine, G.

Abstract

Item does not contain fulltext, 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.

Published
2022

2. 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, Sandarage RV, Phan P, Michalowski W, Van Woensel W, Vig K, Kazley J, Arain A, Rivas G, Ravinsky R, Lawrence J, Gupta S, Patel J, Turkstra I, Pustovetov K, Yang V, Jacobs WB, Mariscal G, Witiw CD, Harrop JS, Essa A, Witiw CD, Mariscal G, Jacobs WB, Harrop JS, Essa A, Du JT, Cherry A, Kumar R, Jaber N, Fehlings M, Yee A, Dukkipati ST, Driscoll M, Byers E, Brown JL, Gallagher M, Sugar J, Rockall S, Hektner J, Donia S, Chernesky J, Noonan VK, Varga AA, Slomp F, Thiessen E, Lastivnyak N, Maclean LS, Ritchie V, Hockley A, Weise LM, Potvin C, Flynn P, Christie S, Turkstra I, Oppermann B, Oppermann M, Gupta S, Patel J, Pustovetov K, Lee K, Chen C, Rastgarjazi M, Yang V, Hardy S, Strantzas S, Anthony A, Dermott J, Vandenberk M, Hassan S, Lebel D, Silva YGMD, LaRue B, Couture J, Pimenta N, Blanchard J, Chenevert A, Goulet J, Greene R, Christie SD, Hall A, Etchegary H, Althagafi A, Han J, Greene R, Christie S, Pickett G, Witiw C, Harrop J, Jacobs WB, Mariscal G, Essa A, Jacobs WB, Mariscal G, Witiw C, Harrop JS, Essa A, Lasswell T, Rasoulinejad P, Hu R, Bailey C, Siddiqi F, Hamdoon A, Soliman MA, Maraj J, Jhawar D, Jhawar B, Schuler KA, Orosz LD, Yamout T, Allen BJ, Lerebo WT, Roy RT, Schuler TC, Good CR, Haines CM, Jazini E, Ost KJ, Al-Shawwa A, Anderson D, Evaniew N, Jacobs BW, Lewkonia P, Nicholls F, Salo PT, Thomas KC, Yang M, Cadotte D, Sarraj M, Rajapaksege N, Dea N, Evaniew N, McIntosh G, Pahuta M, Alharbi HN, Skaik K, Wai EK, Kingwell S, Stratton A, Tsai E, Phan PTN, Wang Z, Investigators C, Zaldivar-Jolissaint JF, Gustafson S, Polyzois I, Gascoyne T, Goytan M, Bednar DA, Sarra M, Rocos B, Sardi JP, Charalampidis A, Gum J, Lewis SJ, Ghag R, Kirk S, Shirley O, Bone J, Morrison A, Miyanji F, Parekh A, Sanders E, Birk M, Nicholls F, Smit K, Livock H, Romeo J, Jarvis J, Tice A, Frank S, Labelle H, Parent S, Barchi S, Joncas J, Mac-Thiong JM, Thibault J, Joncas J, Barchi S, Parent S, Beausejour M, Mac-Thiong JM, Dionne A, Mac-Thiong JM, Parent S, Shen J, Joncas J, Barchi S, Labelle H, Birk MS, Nicholls F, Pelletier-Roy R, Sanders E, Lewis S, Aljamaan Y, Lenke LG, Smith J, Sardar Z, Mullaj E, Lebel D, Dermott J, Bath N, Mathias K, Kattail D, Zohar A, Loomans J, Pellise F, Smith JS, Kato S, Sardar Z, Lenke L, Lewis SJ, Bader TJ, Dhiman M, Hart D, Duncan N, Salo P, Swamy G, Lewis SJ, Lawrence PL, Smith J, Pellise F, Sardar Z, Lawrence PL, Lewis SJ, Smith J, Pellise F, Sardar Z, Levett JJ, Alnasser A, Barak U, Elkaim LM, Hoang TS, Alotaibi NM, Guha D, Moss IL, Weil AG, Weber MH, de Muelenaere P, Parvez K, Sun J, Iorio OC, Rosenstein B, Naghdi N, Fortin M, Manocchio F, Ankory R, Stallwood L, Ahn H, Mahdi H, Naeem A, Jhawar D, Moradi M, Jhawar B, Qiu S, Surendran V, Shi V, Cheung E, Ngana S, Qureshi MA, Sharma SV, Pahuta M, and Guha D

Published
2024
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3. A spinal cord neuroprosthesis for locomotor deficits due to Parkinson's disease.

Author

Milekovic T, Moraud EM, Macellari N, Moerman C, Raschellà F, Sun S, Perich MG, Varescon C, Demesmaeker R, Bruel A, Bole-Feysot LN, Schiavone G, Pirondini E, YunLong C, Hao L, Galvez A, Hernandez-Charpak SD, Dumont G, Ravier J, Le Goff-Mignardot CG, Mignardot JB, Carparelli G, Harte C, Hankov N, Aureli V, Watrin A, Lambert H, Borton D, Laurens J, Vollenweider I, Borgognon S, Bourre F, Goillandeau M, Ko WKD, Petit L, Li Q, Buschman R, Buse N, Yaroshinsky M, Ledoux JB, Becce F, Jimenez MC, Bally JF, Denison T, Guehl D, Ijspeert A, Capogrosso M, Squair JW, Asboth L, Starr PA, Wang DD, Lacour SP, Micera S, Qin C, Bloch J, Bezard E, and Courtine G

Subjects
Male, Animals, Humans, Gait physiology, Spinal Cord, Parkinson Disease complications, Parkinson Disease therapy, Gait Disorders, Neurologic etiology, Gait Disorders, Neurologic therapy, Deep Brain Stimulation
Abstract

People with late-stage Parkinson's disease (PD) often suffer from debilitating locomotor deficits that are resistant to currently available therapies. To alleviate these deficits, we developed a neuroprosthesis operating in closed loop that targets the dorsal root entry zones innervating lumbosacral segments to reproduce the natural spatiotemporal activation of the lumbosacral spinal cord during walking. We first developed this neuroprosthesis in a non-human primate model that replicates locomotor deficits due to PD. This neuroprosthesis not only alleviated locomotor deficits but also restored skilled walking in this model. We then implanted the neuroprosthesis in a 62-year-old male with a 30-year history of PD who presented with severe gait impairments and frequent falls that were medically refractory to currently available therapies. We found that the neuroprosthesis interacted synergistically with deep brain stimulation of the subthalamic nucleus and dopaminergic replacement therapies to alleviate asymmetry and promote longer steps, improve balance and reduce freezing of gait. This neuroprosthesis opens new perspectives to reduce the severity of locomotor deficits in people with PD., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Published
2023
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4. Walking naturally after spinal cord injury using a brain-spine interface.

Author

Lorach H, Galvez A, Spagnolo V, Martel F, Karakas S, Intering N, Vat M, Faivre O, Harte C, Komi S, Ravier J, Collin T, Coquoz L, Sakr I, Baaklini E, Hernandez-Charpak SD, Dumont G, Buschman R, Buse N, Denison T, van Nes I, Asboth L, Watrin A, Struber L, Sauter-Starace F, Langar L, Auboiroux V, Carda S, Chabardes S, Aksenova T, Demesmaeker R, Charvet G, Bloch J, and Courtine G

Subjects
Humans, Quadriplegia etiology, Quadriplegia rehabilitation, Quadriplegia therapy, Reproducibility of Results, Leg physiology, Male, Brain physiology, Brain-Computer Interfaces, Electric Stimulation Therapy instrumentation, Electric Stimulation Therapy methods, Spinal Cord physiology, Spinal Cord Injuries complications, Spinal Cord Injuries rehabilitation, Spinal Cord Injuries therapy, Walking physiology, Neurological Rehabilitation instrumentation, Neurological Rehabilitation methods
Abstract

A spinal cord injury interrupts the communication between the brain and the region of the spinal cord that produces walking, leading to paralysis 1,2 . Here, we restored this communication with a digital bridge between the brain and spinal cord that enabled an individual with chronic tetraplegia to stand and walk naturally in community settings. This brain-spine interface (BSI) consists of fully implanted recording and stimulation systems that establish a direct link between cortical signals 3 and the analogue modulation of epidural electrical stimulation targeting the spinal cord regions involved in the production of walking 4-6 . A highly reliable BSI is calibrated within a few minutes. This reliability has remained stable over one year, including during independent use at home. The participant reports that the BSI enables natural control over the movements of his legs to stand, walk, climb stairs and even traverse complex terrains. Moreover, neurorehabilitation supported by the BSI improved neurological recovery. The participant regained the ability to walk with crutches overground even when the BSI was switched off. This digital bridge establishes a framework to restore natural control of movement after paralysis., (© 2023. The Author(s).)

Published
2023
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5. Targeted dorsal root entry zone stimulation alleviates pain due to meralgia paresthetica.

Author

Aureli V, Vat M, Hankov N, Théaudin M, Ravier J, Becce F, Demesmaeker R, Asboth L, Courtine G, and Bloch J

Subjects
Humans, Female, Quality of Life, Pain, Spinal Nerve Roots, Femoral Neuropathy, Nerve Compression Syndromes complications, Nerve Compression Syndromes diagnosis, Nerve Compression Syndromes therapy
Abstract

Objective. Meralgia paresthetica (MP) is a mononeuropathy of the exclusively sensory lateral femoral cutaneous nerve (LFCN) that is difficult to treat with conservative treatments. Afferents from the LFCN enter the spinal cord through the dorsal root entry zones (DREZs) innervating L2 and L3 spinal segments. We previously showed that epidural electrical stimulation of the spinal cord can be configured to steer electrical currents laterally in order to target afferents within individual DREZs. Therefore, we hypothesized that this neuromodulation strategy is suitable to target the L2 and L3 DREZs that convey afferents from the painful territory, and thus alleviates MP related pain. Approach. A patient in her mid-30s presented with a four year history of dysesthesia and burning pain in the anterolateral aspect of the left thigh due to MP that was refractory to medical treatments. We combined neuroimaging and intraoperative neuromonitoring to guide the surgical placement of a paddle lead over the left DREZs innervating L2 and L3 spinal segments. Main results. Optimized electrode configurations targeting the left L2 and L3 DREZs mediated immediate and sustained alleviation of pain. The patient ceased all other medical management, reported improved quality of life, and resumed recreational physical activities. Significance. We introduced a new treatment option to alleviate pain due to MP, and demonstrated how neuromodulation strategies targeting specific DREZs is effective to reduce pain confined to specific regions of the body while avoiding disconfort., (© 2022 IOP Publishing Ltd.)

Published
2022
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6. The neurons that restore walking after paralysis.

Author

Kathe C, Skinnider MA, Hutson TH, Regazzi N, Gautier M, Demesmaeker R, Komi S, Ceto S, James ND, Cho N, Baud L, Galan K, Matson KJE, Rowald A, Kim K, Wang R, Minassian K, Prior JO, Asboth L, Barraud Q, Lacour SP, Levine AJ, Wagner F, Bloch J, Squair JW, and Courtine G

Subjects
Animals, Humans, Mice, Electric Stimulation, Lumbosacral Region innervation, Neurological Rehabilitation, Sequence Analysis, RNA, Gene Expression Profiling, Neurons physiology, Paralysis genetics, Paralysis physiopathology, Paralysis therapy, Spinal Cord cytology, Spinal Cord physiology, Spinal Cord physiopathology, Spinal Cord Injuries genetics, Spinal Cord Injuries physiopathology, Spinal Cord Injuries therapy, Walking physiology
Abstract

A spinal cord injury interrupts pathways from the brain and brainstem that project to the lumbar spinal cord, leading to paralysis. Here we show that spatiotemporal epidural electrical stimulation (EES) of the lumbar spinal cord 1-3 applied during neurorehabilitation 4,5 (EES REHAB ) restored walking in nine individuals with chronic spinal cord injury. This recovery involved a reduction in neuronal activity in the lumbar spinal cord of humans during walking. We hypothesized that this unexpected reduction reflects activity-dependent selection of specific neuronal subpopulations that become essential for a patient to walk after spinal cord injury. To identify these putative neurons, we modelled the technological and therapeutic features underlying EES REHAB in mice. We applied single-nucleus RNA sequencing 6-9 and spatial transcriptomics 10,11 to the spinal cords of these mice to chart a spatially resolved molecular atlas of recovery from paralysis. We then employed cell type 12,13 and spatial prioritization to identify the neurons involved in the recovery of walking. A single population of excitatory interneurons nested within intermediate laminae emerged. Although these neurons are not required for walking before spinal cord injury, we demonstrate that they are essential for the recovery of walking with EES following spinal cord injury. Augmenting the activity of these neurons phenocopied the recovery of walking enabled by EES REHAB , whereas ablating them prevented the recovery of walking that occurs spontaneously after moderate spinal cord injury. We thus identified a recovery-organizing neuronal subpopulation that is necessary and sufficient to regain walking after paralysis. Moreover, our methodology establishes a framework for using molecular cartography to identify the neurons that produce complex behaviours., (© 2022. The Author(s).)

Published
2022
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7. Implanted System for Orthostatic Hypotension in Multiple-System Atrophy.

Author

Squair JW, Berney M, Castro Jimenez M, Hankov N, Demesmaeker R, Amir S, Paley A, Hernandez-Charpak S, Dumont G, Asboth L, Allenbach G, Becce F, Schoettker P, Wuerzner G, Bally JF, Courtine G, and Bloch J

Subjects
Accelerometry, Atrophy, Blood Pressure physiology, Electrodes, Implanted, Epidural Space, Humans, Posture physiology, Thoracic Vertebrae, Electric Stimulation Therapy methods, Hypotension, Orthostatic diagnosis, Hypotension, Orthostatic etiology, Hypotension, Orthostatic therapy, Multiple System Atrophy therapy
Abstract

Orthostatic hypotension is a cardinal feature of multiple-system atrophy. The upright posture provokes syncopal episodes that prevent patients from standing and walking for more than brief periods. We implanted a system to restore regulation of blood pressure and enable a patient with multiple-system atrophy to stand and walk after having lost these abilities because of orthostatic hypotension. This system involved epidural electrical stimulation delivered over the thoracic spinal cord with accelerometers that detected changes in body position. (Funded by the Defitech Foundation.)., (Copyright © 2022 Massachusetts Medical Society.)

Published
2022
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8. 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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9. Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury.

Author

Squair JW, Gautier M, Mahe L, Soriano JE, Rowald A, Bichat A, Cho N, Anderson MA, James ND, Gandar J, Incognito AV, Schiavone G, Sarafis ZK, Laskaratos A, Bartholdi K, Demesmaeker R, Komi S, Moerman C, Vaseghi B, Scott B, Rosentreter R, Kathe C, Ravier J, McCracken L, Kang X, Vachicouras N, Fallegger F, Jelescu I, Cheng Y, Li Q, Buschman R, Buse N, Denison T, Dukelow S, Charbonneau R, Rigby I, Boyd SK, Millar PJ, Moraud EM, Capogrosso M, Wagner FB, Barraud Q, Bezard E, Lacour SP, Bloch J, Courtine G, and Phillips AA

Subjects
Animals, Disease Models, Animal, Female, Humans, Male, Neural Pathways, Primates, Rats, Rats, Inbred Lew, Sympathetic Nervous System cytology, Sympathetic Nervous System physiology, Baroreflex, Biomimetics, Hemodynamics, Prostheses and Implants, Spinal Cord Injuries physiopathology, Spinal Cord Injuries therapy
Abstract

Spinal cord injury (SCI) induces haemodynamic instability that threatens survival 1-3 , impairs neurological recovery 4,5 , increases the risk of cardiovascular disease 6,7 , and reduces quality of life 8,9 . Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord 10 , which prevents the natural baroreflex from controlling these circuits to adjust peripheral vascular resistance. Epidural electrical stimulation (EES) of the spinal cord has been shown to compensate for interrupted supraspinal commands to motor circuits below the injury 11 , and restored walking after paralysis 12 . Here, we leveraged these concepts to develop EES protocols that restored haemodynamic stability after SCI. We established a preclinical model that enabled us to dissect the topology and dynamics of the sympathetic circuits, and to understand how EES can engage these circuits. We incorporated these spatial and temporal features into stimulation protocols to conceive a clinical-grade biomimetic haemodynamic regulator that operates in a closed loop. This 'neuroprosthetic baroreflex' controlled haemodynamics for extended periods of time in rodents, non-human primates and humans, after both acute and chronic SCI. We will now conduct clinical trials to turn the neuroprosthetic baroreflex into a commonly available therapy for people with SCI.

Published
2021
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10. Deep Learning to Automate Reference-Free Image Quality Assessment of Whole-Heart MR Images.

Author

Piccini D, Demesmaeker R, Heerfordt J, Yerly J, Di Sopra L, Masci PG, Schwitter J, Van De Ville D, Richiardi J, Kober T, and Stuber M

Abstract

Purpose: To develop and characterize an algorithm that mimics human expert visual assessment to quantitatively determine the quality of three-dimensional (3D) whole-heart MR images., Materials and Methods: In this study, 3D whole-heart cardiac MRI scans from 424 participants (average age, 57 years ± 18 [standard deviation]; 66.5% men) were used to generate an image quality assessment algorithm. A deep convolutional neural network for image quality assessment (IQ-DCNN) was designed, trained, optimized, and cross-validated on a clinical database of 324 (training set) scans. On a separate test set (100 scans), two hypotheses were tested: (a) that the algorithm can assess image quality in concordance with human expert assessment as assessed by human-machine correlation and intra- and interobserver agreement and (b) that the IQ-DCNN algorithm may be used to monitor a compressed sensing reconstruction process where image quality progressively improves. Weighted κ values, agreement and disagreement counts, and Krippendorff α reliability coefficients were reported., Results: Regression performance of the IQ-DCNN was within the range of human intra- and interobserver agreement and in very good agreement with the human expert ( R 2 = 0.78, κ = 0.67). The image quality assessment during compressed sensing reconstruction correlated with the cost function at each iteration and was successfully applied to rank the results in very good agreement with the human expert., Conclusion: The proposed IQ-DCNN was trained to mimic expert visual image quality assessment of 3D whole-heart MR images. The results from the IQ-DCNN were in good agreement with human expert reading, and the network was capable of automatically comparing different reconstructed volumes. Supplemental material is available for this article. © RSNA, 2020., Competing Interests: Disclosures of Conflicts of Interest: D.P. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: employed by and has stock options in Siemens Healthcare; payment from patent with Siemens Healthcare; pending patent (Siemens gives incentive to write patent applications). Other relationships: disclosed no relevant relationships. R.D. disclosed no relevant relationships. J.H. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: author’s PhD studies are financially supported by Siemens Healthcare (Erlangen, Germany). Other relationships: disclosed no relevant relationships. J.Y. disclosed no relevant relationships. L.D.S. disclosed no relevant relationships. P.G.M. disclosed no relevant relationships. J.S. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: institution receives unrestricted grant to support research activity of cardiac MR center. Other relationships: disclosed no relevant relationships. D.V.D.V. disclosed no relevant relationships. J.R. Activities related to the present article: 30% of author’s salary paid by Siemens Healthcare Switzerland; author owns shares in Siemens Healthcare. Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed no relevant relationships. T.K. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: employed by Siemens Healthcare Switzerland; participates in Siemens Healthcare Switzerland employee stock share program. Other relationships: disclosed no relevant relationships. M.S. Activities related to the present article: institution receives grant from Swiss National Science Foundation. Activities not related to the present article: author receives nonmonetary research support from Siemens Healthineers. Other relationships: disclosed no relevant relationships., (2020 by the Radiological Society of North America, Inc.)

Published
2020
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11. Targeted neurotechnology restores walking in humans with spinal cord injury.

Author

Wagner FB, Mignardot JB, Le Goff-Mignardot CG, Demesmaeker R, Komi S, Capogrosso M, Rowald A, Seáñez I, Caban M, Pirondini E, Vat M, McCracken LA, Heimgartner R, Fodor I, Watrin A, Seguin P, Paoles E, Van Den Keybus K, Eberle G, Schurch B, Pralong E, Becce F, Prior J, Buse N, Buschman R, Neufeld E, Kuster N, Carda S, von Zitzewitz J, Delattre V, Denison T, Lambert H, Minassian K, Bloch J, and Courtine G

Subjects
Activities of Daily Living, Computer Simulation, Electromyography, Epidural Space, Humans, Leg innervation, Leg physiology, Leg physiopathology, Locomotion physiology, Male, Motor Neurons physiology, Muscle, Skeletal innervation, Muscle, Skeletal physiology, Muscle, Skeletal physiopathology, Paralysis physiopathology, Paralysis surgery, Spinal Cord cytology, Spinal Cord physiology, Spinal Cord physiopathology, Spinal Cord Injuries physiopathology, Spinal Cord Injuries surgery, Biomedical Technology, Electric Stimulation Therapy, Paralysis rehabilitation, Spinal Cord Injuries rehabilitation, Walking physiology
Abstract

Spinal cord injury leads to severe locomotor deficits or even complete leg paralysis. Here we introduce targeted spinal cord stimulation neurotechnologies that enabled voluntary control of walking in individuals who had sustained a spinal cord injury more than four years ago and presented with permanent motor deficits or complete paralysis despite extensive rehabilitation. Using an implanted pulse generator with real-time triggering capabilities, we delivered trains of spatially selective stimulation to the lumbosacral spinal cord with timing that coincided with the intended movement. Within one week, this spatiotemporal stimulation had re-established adaptive control of paralysed muscles during overground walking. Locomotor performance improved during rehabilitation. After a few months, participants regained voluntary control over previously paralysed muscles without stimulation and could walk or cycle in ecological settings during spatiotemporal stimulation. These results establish a technological framework for improving neurological recovery and supporting the activities of daily living after spinal cord injury.

Published
2018
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