{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:43:04Z","timestamp":1792546984280,"version":"4.5.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T00:00:00Z","timestamp":1625616000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T00:00:00Z","timestamp":1625616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rare neuromuscular diseases such as spinal muscular atrophy, spinal bulbar muscular atrophy, muscular dystrophy, Charcot-Marie-Tooth disease, distal myopathy, sporadic inclusion body myositis, congenital myopathy, and amyotrophic lateral sclerosis lead to incurable amyotrophy and consequent loss of ambulation. Thus far, no therapeutic approaches have been successful in recovering the ambulatory ability. Thus, the aim of this trial was to evaluate the efficacy and safety of cybernic treatment with a wearable cyborg Hybrid Assistive Limb (HAL, Lower Limb Type) in improving the ambulatory function in those patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We conducted an open-label, randomised, controlled crossover trial to test HAL at nine hospitals between March 6, 2013 and August 8, 2014. Eligible patients were older than 18\u00a0years and had a diagnosis of neuromuscular disease as specified above. They were unable to walk for 10\u00a0m independently and had neither respiratory failure nor rapid deterioration in gait. The primary endpoint was the distance passed during a two-minute walk test (2MWT). The secondary endpoints were walking speed, cadence, and step length during the 10-m walk test (10MWT), muscle strength by manual muscle testing (MMT), and a series of functional measures. Adverse events and failures\/problems\/errors with HAL were also evaluated. Thirty patients were randomly assigned to groups A or B, with each group of 15 receiving both treatments in a crossover design. The efficacy of a 40-min walking program performed nine times was compared between HAL plus a hoist and a hoist only. The final analysis included 13 and 11 patients in groups A and B, respectively. Cybernic treatment with HAL resulted in a 10.066% significantly improved distance in 2MWT (95% confidence interval, 0.667\u201319.464;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0369) compared with the hoist only treatment. Among the secondary endpoints, the total scores of MMT and cadence at 10MWT were the only ones that showed significant improvement. The only adverse effects were slight to mild myalgia, back pain, and contact skin troubles, which were easily remedied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HAL is a new treatment device for walking exercise, proven to be more effective than the conventional method in patients with incurable neuromuscular diseases.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>Trial registration<\/jats:italic>\n                      : JMACTR, JMA-IIA00156\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-021-01928-9","type":"journal-article","created":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T07:02:53Z","timestamp":1625641373000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Cybernic treatment with wearable cyborg Hybrid Assistive Limb (HAL) improves ambulatory function in patients with slowly progressive rare neuromuscular diseases: a multicentre, randomised, controlled crossover trial for efficacy and safety (NCY-3001)"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5105-6619","authenticated-orcid":false,"given":"Takashi","family":"Nakajima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Sankai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinjiro","family":"Takata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihito","family":"Ando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayoko","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiho","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Tamaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Saotome","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Ikai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisako","family":"Endo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuya","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Maeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyonobu","family":"Komai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuhiko","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Maeshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiya","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Mima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Miura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Shingu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Kawamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,7]]},"reference":[{"key":"1928_CR1","unstructured":"Sherrington CS. Remarks on some aspects of reflex inhibition; 1925."},{"key":"1928_CR2","doi-asserted-by":"publisher","DOI":"10.1093\/acprof:oso\/9780195065169.001.0001","volume-title":"Cajal's degeneration and regeneration of the nervous system Facsimile of the 1928","author":"S Ram\u00f3n y Cajal","year":"1991","unstructured":"Ram\u00f3n y Cajal S. Cajal\u2019s degeneration and regeneration of the nervous system Facsimile of the 1928. London, New York: Hafner Publishing Company; 1991."},{"key":"1928_CR3","first-page":"1","volume-title":"Brain injury and recovery: theoretical and controversial issues","author":"CR Almli","year":"1988","unstructured":"Almli CR, Stanley F. Toward a definition of recovery of function. In: Almli CR, Finger S, LeVere TE, Stein D, editors. Brain injury and recovery: theoretical and controversial issues. New York: Plenum; 1988. p. 1\u201314."},{"key":"1928_CR4","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1055\/s-0036-1586263","volume":"36","author":"BM Morrison","year":"2016","unstructured":"Morrison BM. Neuromuscular diseases. Semin Neurol. 2016;36:409\u201318.","journal-title":"Semin Neurol"},{"key":"1928_CR5","first-page":"22","volume":"12","author":"RL Bennett","year":"1958","unstructured":"Bennett RL, Knowlton GC. Overwork weakness in partially denervated skeletal muscle. Clin Orthop. 1958;12:22\u20139.","journal-title":"Clin Orthop"},{"key":"1928_CR6","first-page":"333","volume":"52","author":"EW Johnson","year":"1971","unstructured":"Johnson EW, Braddom R. Over-work weakness in facioscapulohuumeral muscular dystrophy. Arch Phys Med Rehabil. 1971;52:333\u20136.","journal-title":"Arch Phys Med Rehabil"},{"key":"1928_CR7","first-page":"CD005229","volume":"5","author":"V Dal Bello-Haas","year":"2013","unstructured":"Dal Bello-Haas V, Florence JM. Therapeutic exercise for people with amyotrophic lateral sclerosis or motor neuron disease. Cochrane Database Syst Rev. 2013;5:CD005229.","journal-title":"Cochrane Database Syst Rev"},{"key":"1928_CR8","doi-asserted-by":"publisher","first-page":"e65414","DOI":"10.1371\/journal.pone.0065414","volume":"8","author":"S Gianola","year":"2013","unstructured":"Gianola S, Pecoraro V, Lambiase S, Gatti R, Banfi G, Moja L. Efficacy of muscle exercise in patients with muscular dystrophy: a systematic review showing a missed opportunity to improve outcomes. PLoS ONE. 2013;8:e65414.","journal-title":"PLoS ONE"},{"key":"1928_CR9","first-page":"CD003907","volume":"7","author":"NB Voet","year":"2013","unstructured":"Voet NB, van der Kooi EL, Riphagen II, Lindeman E, van Engelen BG, Geurts AC. Strength training and aerobic exercise training for muscle disease. Cochrane Database Syst Rev. 2013;7:CD003907.","journal-title":"Cochrane Database Syst Rev"},{"key":"1928_CR10","first-page":"CD012120","volume":"3","author":"B Bartels","year":"2019","unstructured":"Bartels B, Montes J, van der Pol WL, de Groot JF. Physical exercise training for type 3 spinal muscular atrophy. Cochrane Database Syst Rev. 2019;3:CD012120.","journal-title":"Cochrane Database Syst Rev"},{"key":"1928_CR11","first-page":"CD003907","volume":"1","author":"EL van der Kooi","year":"2005","unstructured":"van der Kooi EL, Lindeman E, Riphagen I. Strength training and aerobic exercise training for muscle disease. Cochrane Database Syst Rev. 2005;1:CD003907.","journal-title":"Cochrane Database Syst Rev."},{"key":"1928_CR12","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1056\/NEJMoa1710504","volume":"378","author":"E Mercuri","year":"2018","unstructured":"Mercuri E, Darras BT, Chiriboga CA, Day JW, Campbell C, Connolly AM, et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018;378:625\u201335.","journal-title":"N Engl J Med"},{"key":"1928_CR13","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1007\/s00415-019-09251-x","volume":"266","author":"A Hashizume","year":"2019","unstructured":"Hashizume A, Katsuno M, Suzuki K, Banno H, Takeuchi Y, Kawashima M, et al. Efficacy and safety of leuprorelin acetate for subjects with spinal and bulbar muscular atrophy: pooled analyses of two randomized-controlled trials. J Neurol. 2019;266:1211\u201321.","journal-title":"J Neurol"},{"key":"1928_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jocn.2017.10.082","volume":"49","author":"L Randeree","year":"2018","unstructured":"Randeree L, Eslick GD. Eteplirsen for paediatric patients with Duchenne muscular dystrophy: a pooled-analysis. J Clin Neurosci. 2018;49:1\u20136.","journal-title":"J Clin Neurosci"},{"key":"1928_CR15","doi-asserted-by":"publisher","first-page":"533","DOI":"10.2147\/DDDT.S97635","volume":"11","author":"KR Lim","year":"2017","unstructured":"Lim KR, Maruyama R, Yokota T. Eteplirsen in the treatment of Duchenne muscular dystrophy. Drug Des Devel Ther. 2017;11:533\u201345.","journal-title":"Drug Des Devel Ther"},{"key":"1928_CR16","first-page":"359","volume":"13","author":"Y Sankai","year":"1989","unstructured":"Sankai Y, Ohta M, Kumagai Y. An artificial kidney control system based on a cybernics conception. Artif Organs. 1989;13:359.","journal-title":"Artif Organs"},{"key":"1928_CR17","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1007\/BF02471176","volume":"2","author":"Y Sankai","year":"1998","unstructured":"Sankai Y, Fujiwara K, Watanabe K, Moriyama H. HOJO-brain for motion control of robots and biological systems. Artif Life Robot. 1998;2:162\u20139.","journal-title":"Artif Life Robot"},{"key":"1928_CR18","doi-asserted-by":"crossref","unstructured":"Sankai Y, Ohta M. Therapeutic robot system during hemopurification aimed at human oriented system. In: Proceedings of the IEEE international workshop on intelligent motion control. vol 1; 1990. p. 247\u201351.","DOI":"10.1109\/IMC.1990.687325"},{"key":"1928_CR19","doi-asserted-by":"crossref","unstructured":"Sankai Y. HAL: Hybrid Assistive Limb based on cybernics. In: Robotic research, The 13th international symposium ISRR 2010:25-34.","DOI":"10.1007\/978-3-642-14743-2_3"},{"key":"1928_CR20","doi-asserted-by":"publisher","DOI":"10.1007\/978-4-431-54159-2","volume-title":"Cybernics: fusion of human, machine and information systems","author":"Y Sankai","year":"2014","unstructured":"Sankai Y, Suzuki K, Hasegawa Y. Cybernics: fusion of human, machine and information systems. Tokyo: Springer; 2014."},{"key":"1928_CR21","first-page":"16","volume":"106","author":"M Lazarte","year":"2014","unstructured":"Lazarte M. Enter the first cyborg-type robot. ISOfocus. 2014;106:16\u201321.","journal-title":"ISOfocus"},{"key":"1928_CR22","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1177\/1545968312448232","volume":"26","author":"M Alcobendas-Maestro","year":"2012","unstructured":"Alcobendas-Maestro M, Esclarin-Ruz A, Casado-Lopez RM, Munoz-Gonzalez A, Perez-Mateos G, Gonzalez-Valdizan E, et al. Lokomat robotic-assisted versus overground training within 3 to 6 months of incomplete spinal cord lesion: randomized controlled trial. Neurorehabil Neural Repair. 2012;26:1058\u201363.","journal-title":"Neurorehabil Neural Repair"},{"key":"1928_CR23","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s12984-019-0585-x","volume":"16","author":"AS Khan","year":"2019","unstructured":"Khan AS, Livingstone DC, Hurd CL, Duchcherer J, Misiaszek JE, Gorassini MA, et al. Retraining walking over ground in a powered exoskeleton after spinal cord injury: a prospective cohort study to examine functional gains and neuroplasticity. J Neuroeng Rehabil. 2019;16:145.","journal-title":"J Neuroeng Rehabil"},{"key":"1928_CR24","doi-asserted-by":"crossref","unstructured":"Hayashi T, Kawamoto H, Sankai Y. Control method of robot suit HAL working as operator's muscle using biological and dynamical information. In: 2005 IEEE\/RSJ international conference on intelligent robots and systems. 2005; p. 3063\u201368.","DOI":"10.1109\/IROS.2005.1545505"},{"key":"1928_CR25","first-page":"462","volume":"2010","author":"H Kawamoto","year":"2010","unstructured":"Kawamoto H, Taal S, Niniss H, Hayashi T, Kamibayashi K, Eguchi K, et al. Voluntary motion support control of Robot Suit HAL triggered by bioelectrical signal for hemiplegia. Conf Proc IEEE Eng Med Biol Soc. 2010;2010:462\u20136.","journal-title":"Conf Proc IEEE Eng Med Biol Soc"},{"key":"1928_CR26","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1016\/j.apmr.2012.12.020","volume":"94","author":"S Kubota","year":"2013","unstructured":"Kubota S, Nakata Y, Eguchi K, Kawamoto H, Kamibayashi K, Sakane M, et al. Feasibility of rehabilitation training with a newly developed wearable robot for patients with limited mobility. Arch Phys Med Rehabil. 2013;94:1080\u20137.","journal-title":"Arch Phys Med Rehabil"},{"key":"1928_CR27","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1109\/TNSRE.2014.2364618","volume":"23","author":"A Tsukahara","year":"2015","unstructured":"Tsukahara A, Hasegawa Y, Eguchi K, Sankai Y. Restoration of gait for spinal cord injury patients using HAL with intention estimator for preferable swing speed. IEEE Trans Neural Syst Rehabil Eng. 2015;23:308\u201318.","journal-title":"IEEE Trans Neural Syst Rehabil Eng"},{"key":"1928_CR28","first-page":"90","volume":"16","author":"Y Sankai","year":"2017","unstructured":"Sankai Y, Sakurai T. Functional regenerative medicine: the dawn of \u201c Cybernic Treatment.\u201d Regen Med. 2017;16:90\u2013101 (in Japanese).","journal-title":"Regen Med"},{"key":"1928_CR29","first-page":"596","volume":"86","author":"Y Sankai","year":"2017","unstructured":"Sankai Y, Sakurai T. Future of cybernics and treatment of neurological disorders: functional regenerative treatment with HAL. Neurol Med. 2017;86:596\u2013603 (in Japanese).","journal-title":"Neurol Med"},{"key":"1928_CR30","first-page":"583","volume":"86","author":"T Nakajima","year":"2017","unstructured":"Nakajima T. Aplications of cybernics to treatment of neurological diseases-the future perspectives and sugestions from the experience of the investigator-initiated & GCP-regulated clinical trial of the cyborg type HAL. Neurol Med. 2017;86:583\u20139 (in Japanese).","journal-title":"Neurol Med"},{"key":"1928_CR31","unstructured":"Bernstein NA. On dexterity and its development. Dexterity and its development 1996:3\u2013236."},{"key":"1928_CR32","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1097\/MRR.0b013e32831e4546","volume":"32","author":"K Kawahira","year":"2009","unstructured":"Kawahira K, Noma T, Iiyama J, Etoh S, Ogata A, Shimodozono M. Improvements in limb kinetic apraxia by repetition of a newly designed facilitation exercise in a patient with corticobasal degeneration. Int J Rehabil Res. 2009;32:178\u201383.","journal-title":"Int J Rehabil Res"},{"key":"1928_CR33","doi-asserted-by":"publisher","first-page":"871296","DOI":"10.1155\/2011\/871296","volume":"2011","author":"JA Hosp","year":"2011","unstructured":"Hosp JA, Luft AR. Cortical plasticity during motor learning and recovery after ischemic stroke. Neural Plast. 2011;2011:871296.","journal-title":"Neural Plast"},{"key":"1928_CR34","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3389\/fneur.2013.00191","volume":"4","author":"T Isa","year":"2013","unstructured":"Isa T, Kinoshita M, Nishimura Y. Role of direct vs. indirect pathways from the motor cortex to spinal motoneurons in the control of hand dexterity. Front Neurol. 2013;4:191.","journal-title":"Front Neurol"},{"key":"1928_CR35","first-page":"130","volume":"60","author":"T Nakajima","year":"2011","unstructured":"Nakajima T. Clinical trial of robot suit HAL technology for neuromuscular intractable rare diseases. J Natl Inst Public Health Jpn. 2011;60:130\u20137 (in Japanese).","journal-title":"J Natl Inst Public Health Jpn."},{"key":"1928_CR36","volume-title":"Humans & machines in medical contexts\u2014case studies from Japan","author":"T Nakajima","year":"2021","unstructured":"Nakajima T. Chapter 11, Innovative technology, clinical trials and the subjective evaluation of patients: the cyborg- type robot HAL and the treatment of functional regeneration in patients with rare incurable neuromuscular diseases in Japan. In: Brucksch S, Sasaki K, editors. Humans & machines in medical contexts\u2014case studies from Japan. London: Palgrave Macmillan; 2021."},{"key":"1928_CR37","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1212\/WNL.0000000000002332","volume":"86","author":"LK Andersen","year":"2016","unstructured":"Andersen LK, Knak KL, Witting N, Vissing J. Two- and 6-minute walk tests assess walking capability equally in neuromuscular diseases. Neurology. 2016;86:442\u20135.","journal-title":"Neurology"},{"key":"1928_CR38","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1177\/0269215509339004","volume":"23","author":"S Tyson","year":"2009","unstructured":"Tyson S, Connell L. The psychometric properties and clinical utility of measures of walking and mobility in neurological conditions: a systematic review. Clin Rehabil. 2009;23:1018\u201333.","journal-title":"Clin Rehabil"},{"key":"1928_CR39","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1191\/026921598666182531","volume":"12","author":"SE Lord","year":"1998","unstructured":"Lord SE, Halligan PW, Wade DT. Visual gait analysis: the development of a clinical assessment and scale. Clin Rehabil. 1998;12:107\u201319.","journal-title":"Clin Rehabil"},{"issue":"Suppl","key":"1928_CR40","doi-asserted-by":"publisher","first-page":"S16","DOI":"10.1002\/mus.880131307","volume":"13","author":"JR Mendell","year":"1990","unstructured":"Mendell JR, Florence J. Manual muscle testing. Muscle Nerve. 1990;13(Suppl):S16-20.","journal-title":"Muscle Nerve"},{"key":"1928_CR41","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s40520-016-0558-x","volume":"29","author":"T Saito","year":"2017","unstructured":"Saito T, Izawa KP, Matsui N, Arai K, Ando M, Morimoto K, et al. Comparison of the measurement properties of the functional independence and difficulty scale with the Barthel Index in community-dwelling elderly people in Japan. Aging Clin Exp Res. 2017;29:273\u201381.","journal-title":"Aging Clin Exp Res"},{"key":"1928_CR42","first-page":"276","volume":"109","author":"S Wellek","year":"2012","unstructured":"Wellek S, Blettner M. On the proper use of the crossover design in clinical trials: part 18 of a series on evaluation of scientific publications. Dtsch Arztebl Int. 2012;109:276\u201381.","journal-title":"Dtsch Arztebl Int"},{"key":"1928_CR43","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1080\/16501970410023461","volume":"36","author":"K Uchikawa","year":"2004","unstructured":"Uchikawa K, Liu M, Hanayama K, Tsuji T, Fujiwara T, Chino N. Functional status and muscle strength in people with Duchenne muscular dystrophy living in the community. J Rehabil Med. 2004;36:124\u20139.","journal-title":"J Rehabil Med"},{"key":"1928_CR44","unstructured":"CYBERDYNE. Longterm outcome survey of \"HAL for Medical Use (Lower Limb Type)\" , JMA-IIA00301 2017. https:\/\/dbcentre3.jmacct.med.or.jp\/JMACTR\/App\/JMACTRE02_04\/JMACTRE02_04.aspx?kbn=3&seqno=6950. Accessed 9 May 2021."},{"key":"1928_CR45","doi-asserted-by":"publisher","first-page":"11131","DOI":"10.1523\/JNEUROSCI.4674-13.2014","volume":"34","author":"S Sasada","year":"2014","unstructured":"Sasada S, Kato K, Kadowaki S, Groiss SJ, Ugawa Y, Komiyama T, et al. Volitional walking via upper limb muscle-controlled stimulation of the lumbar locomotor center in man. J Neurosci. 2014;34:11131\u201342.","journal-title":"J Neurosci"},{"key":"1928_CR46","doi-asserted-by":"publisher","first-page":"116939","DOI":"10.1016\/j.jns.2020.116939","volume":"415","author":"D Ando","year":"2020","unstructured":"Ando D, Yokota C, Koshino K, Yasuno F, Sato T, Yamamoto A, et al. Microstructural white matter changes following gait training with Hybrid Assistive Limb initiated within 1 week of stroke onset. J Neurol Sci. 2020;415:116939.","journal-title":"J Neurol Sci"},{"key":"1928_CR47","doi-asserted-by":"publisher","first-page":"48","DOI":"10.3389\/fnsys.2015.00048","volume":"9","author":"A Wall","year":"2015","unstructured":"Wall A, Borg J, Palmcrantz S. Clinical application of the Hybrid Assistive Limb (HAL) for gait training-a systematic review. Front Syst Neurosci. 2015;9:48.","journal-title":"Front Syst Neurosci"},{"key":"1928_CR48","doi-asserted-by":"publisher","first-page":"e14001","DOI":"10.2196\/14001","volume":"8","author":"H Tsurushima","year":"2019","unstructured":"Tsurushima H, Mizukami M, Yoshikawa K, Ueno T, Hada Y, Gosho M, et al. Effectiveness of a walking program involving the Hybrid Assistive Limb robotic exoskeleton suit for improving walking ability in sroke patients: protocol for a randomized controlled trial. JMIR Res Protoc. 2019;8:e14001.","journal-title":"JMIR Res Protoc"},{"key":"1928_CR49","doi-asserted-by":"publisher","first-page":"259","DOI":"10.3389\/fnins.2019.00259","volume":"13","author":"M Sczesny-Kaiser","year":"2019","unstructured":"Sczesny-Kaiser M, Trost R, Aach M, Schildhauer TA, Schwenkreis P, Tegenthoff M. A randomized and controlled crossover study investigating the improvement of walking and posture functions in chronic stroke patients using HAL exoskeleton\u2014the HALESTRO study (HALexoskeleton STROke study). Front Neurosci. 2019;13:259.","journal-title":"Front Neurosci"},{"key":"1928_CR50","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.jns.2019.07.012","volume":"404","author":"C Yokota","year":"2019","unstructured":"Yokota C, Yamamoto Y, Kamada M, Nakai M, Nishimura K, Ando D, et al. Acute stroke rehabilitation for gait training with cyborg type robot Hybrid Assistive Limb: a pilot study. J Neurol Sci. 2019;404:11\u20135.","journal-title":"J Neurol Sci"},{"key":"1928_CR51","doi-asserted-by":"publisher","first-page":"e73","DOI":"10.1016\/j.wneu.2017.10.080","volume":"110","author":"O Jansen","year":"2018","unstructured":"Jansen O, Grasmuecke D, Meindl RC, Tegenthoff M, Schwenkreis P, Sczesny-Kaiser M, et al. Hybrid Assistive Limb exoskeleton HAL in the rehabilitation of chronic spinal cord injury: proof of concept; the results in 21 patients. World Neurosurg. 2018;110:e73\u20138.","journal-title":"World Neurosurg"},{"key":"1928_CR52","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1038\/s41393-019-0403-0","volume":"58","author":"H Okawara","year":"2020","unstructured":"Okawara H, Sawada T, Matsubayashi K, Sugai K, Tsuji O, Nagoshi N, et al. Gait ability required to achieve therapeutic effect in gait and balance function with the voluntary driven exoskeleton in patients with chronic spinal cord injury: a clinical study. Spinal Cord. 2020;58:520\u20137.","journal-title":"Spinal Cord"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-01928-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-021-01928-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-01928-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T11:51:49Z","timestamp":1725364309000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-021-01928-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,7]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1928"],"URL":"https:\/\/doi.org\/10.1186\/s13023-021-01928-9","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,7]]},"assertion":[{"value":"24 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The internal review boards of all clinical sites approved this trial, and the protocol was completely reviewed and approved by the Japanese authority, Pharmaceutical and Medical Devices Agency (PMDA). This trial fully complied with the ordinance for medical device GCP (Good Clinical Practice) and was inspected by the PMDA.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"TN, ST, MN, TSai, KS, AT, TIka, HE, KI, and TIke report grants from MHLW & AMED, non-financial support such as temporary use of the investigation device, HAL-HN01 from CYBERDYNE. Inc., during the conducting of the study. YKo, YA, TSao, CI, TMae, MM, and KK report grants from MHLW, non-financial support such as temporary use of the investigation device, HAL-HN01 from CYBERDYNE. Inc., during the conducting of the study. YI, SM, MA, MI, TMim, TMiu, JM, and YKa report grants from MHLW & AMED during the conducting of the study. HK and YS report grants from MHLW & AMED during the conducting of the study and personal fees from CYBERDYNE. Inc. unrelated to the submitted work. MSh and TH report grants from MHLW & AMED, personal fees from CYBERDYNE, Inc., during the conducting of the study, and personal fees from CYBERDYNE, Inc. unrelated to the submitted work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"304"}}