{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:47:53Z","timestamp":1790380073368,"version":"4.1.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Bonn"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol. Res. Pract."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nitrous oxide (N\u2082O), commonly known as laughing gas, is widely recognized for its anesthetic and analgesic effects, and is frequently used in medical contexts. However, its misuse can lead to significant neurological complications, which are often under-recognized in clinical practice. Recent data on such cases in Germany are rare. We here report the spectrum of neurological complications associated with the recreational use of N\u2082O, as encountered in German neurology centers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed of 23 cases presenting with neurological symptoms following N\u2082O abuse between July 2020 and August 2024 across five neurology departments in Germany. Data were collected on patient demographics, clinical manifestations, diagnostic findings, and treatment approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Over the last four years the number of cases increased. Clinical presentations primarily included neuropathy, found in all patients, along with myelopathy. The most common symptoms were sensory loss, ataxia, and motor deficits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data suggest that N\u2082O abuse is on the rise in Germany. Further initiatives are warranted to raise awareness among users, healthcare and professionals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s42466-024-00361-0","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T18:01:15Z","timestamp":1736964075000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Increase of nitrous oxide-induced neurological disorders \u2013 a German multicenter experience"],"prefix":"10.1186","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8980-9337","authenticated-orcid":false,"given":"Julius Nicolai","family":"Mei\u00dfner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina","family":"Neuneier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iason","family":"Bartzokis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Rehm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Al-Hayali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Paus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Limmroth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gereon R.","family":"Fink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabor C.","family":"Petzold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louisa","family":"Nitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"issue":"6","key":"361_CR1","doi-asserted-by":"publisher","first-page":"3340","DOI":"10.1007\/s00415-024-12264-w","volume":"271","author":"Y Dawudi","year":"2024","unstructured":"Dawudi, Y., Azoyan, L., Broucker, T. D. E., Gendre, T., Miloudi, A., Echaniz-Laguna, A., Mazoyer, J., Zanin, A., Kubis, N., Dubessy, A. L., Gorza, L., Nasr, B., Car\u00e9, H., d\u2019Izarny-Gargas, W., Formoso, T., Vilcu, A., A.\u2013M., & Bonnan, M. (2024). Marked increase in severe neurological disorders after nitrous oxide abuse: A retrospective study in the Greater Paris area. Journal of Neurology, 271(6), 3340\u20133346. https:\/\/doi.org\/10.1007\/s00415-024-12264-w","journal-title":"Journal of Neurology"},{"issue":"7","key":"361_CR2","doi-asserted-by":"publisher","first-page":"2621","DOI":"10.1007\/s10072-023-06660-9","volume":"44","author":"N Gancarczyk","year":"2023","unstructured":"Gancarczyk, N., Lakghomi, A., & Kaut, O. (2023). Nitrous oxide-induced funicular myelosis and polyneuropathy: A case report with follow-up MR imaging. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 44(7), 2621\u20132623. https:\/\/doi.org\/10.1007\/s10072-023-06660-9","journal-title":"Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology"},{"key":"361_CR3","doi-asserted-by":"publisher","first-page":"626174","DOI":"10.3389\/fneur.2021.626174","volume":"12","author":"H Gao","year":"2021","unstructured":"Gao, H., Li, W., Ren, J., Dong, X., Ma, Y., & Zheng, D. (2021). Clinical and MRI differences between patients with Subacute Combined Degeneration of the spinal cord related vs. unrelated to recreational Nitrous Oxide Use: A retrospective study. Frontiers in Neurology, 12, 626174. https:\/\/doi.org\/10.3389\/fneur.2021.626174","journal-title":"Frontiers in Neurology"},{"issue":"1\u20132","key":"361_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jns.2010.10.033","volume":"301","author":"L Hathout","year":"2011","unstructured":"Hathout, L., & El-Saden, S. (2011). Nitrous oxide-induced B\u2081\u2082 deficiency myelopathy: Perspectives on the clinical biochemistry of vitamin B\u2081\u2082. Journal of the Neurological Sciences, 301(1\u20132), 1\u20138. https:\/\/doi.org\/10.1016\/j.jns.2010.10.033","journal-title":"Journal of the Neurological Sciences"},{"key":"361_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/7468506","volume":"2020","author":"A Jarquin Campos","year":"2020","unstructured":"Jarquin Campos, A., Risch, L., Nydegger, U., Wiesner, J., van Vazquez Dyck, M., Renz, H., Stanga, Z., & Risch, M. (2020). Diagnostic accuracy of Holotranscobalamin, vitamin B12, Methylmalonic Acid, and Homocysteine in Detecting B12 Deficiency in a large, mixed patient Population. Disease Markers, 2020, 1\u201311. https:\/\/doi.org\/10.1155\/2020\/7468506","journal-title":"Disease Markers"},{"issue":"3","key":"361_CR6","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.neuroscience.2003.07.012","volume":"122","author":"V Jevtovic-Todorovic","year":"2003","unstructured":"Jevtovic-Todorovic, V., Beals, J., Benshoff, N., & Olney, J. W. (2003). Prolonged exposure to inhalational anesthetic nitrous oxide kills neurons in adult rat brain. Neuroscience, 122(3), 609\u2013616. https:\/\/doi.org\/10.1016\/j.neuroscience.2003.07.012","journal-title":"Neuroscience"},{"issue":"4","key":"361_CR7","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/nm0498-460","volume":"4","author":"V Jevtovi\u0107-Todorovi\u0107","year":"1998","unstructured":"Jevtovi\u0107-Todorovi\u0107, V., Todorovi\u0107, S. M., Mennerick, S., Powell, S., Dikranian, K., Benshoff, N., Zorumski, C. F., & Olney, J. W. (1998). Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nature Medicine, 4(4), 460\u2013463. https:\/\/doi.org\/10.1038\/nm0498-460","journal-title":"Nature Medicine"},{"issue":"4","key":"361_CR8","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1177\/0269881116632375","volume":"30","author":"SJ Kaar","year":"2016","unstructured":"Kaar, S. J., Ferris, J., Waldron, J., Devaney, M., Ramsey, J., & Winstock, A. R. (2016). Up: The rise of nitrous oxide abuse. An international survey of contemporary nitrous oxide use. Journal of Psychopharmacology (Oxford England), 30(4), 395\u2013401. https:\/\/doi.org\/10.1177\/0269881116632375","journal-title":"Journal of Psychopharmacology (Oxford England)"},{"issue":"12","key":"361_CR9","doi-asserted-by":"publisher","first-page":"2356","DOI":"10.1515\/cclm-2023-1252","volume":"62","author":"A Lucas","year":"2024","unstructured":"Lucas, A., Noyce, A. J., Gernez, E., Khoury, E., Garcon, J. M., Cavalier, G., Antherieu, E., S., & Grzych, G. (2024). Nitrous oxide abuse direct measurement for diagnosis and follow-up: Update on kinetics and impact on metabolic pathways. Clinical Chemistry and Laboratory Medicine, 62(12), 2356\u20132372. https:\/\/doi.org\/10.1515\/cclm-2023-1252","journal-title":"Clinical Chemistry and Laboratory Medicine"},{"issue":"9","key":"361_CR10","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1136\/jnnp-2023-331131","volume":"94","author":"D Mair","year":"2023","unstructured":"Mair, D., Paris, A., Zaloum, S. A., White, L. M., Dodd, K. C., Englezou, C., Patel, F., Abualnaja, S., Lilleker, J. B., Gosal, D., Hayton, T., Di Liang, Allroggen, H., Pucci, M., Keddie, S., & Noyce, A. J. (2023). Nitrous oxide-induced myeloneuropathy: A case series. Journal of Neurology Neurosurgery and Psychiatry, 94(9), 681\u2013688. https:\/\/doi.org\/10.1136\/jnnp-2023-331131","journal-title":"Journal of Neurology Neurosurgery and Psychiatry"},{"issue":"Suppl 1","key":"361_CR11","doi-asserted-by":"publisher","first-page":"S65","DOI":"10.1016\/S0140-6736(23)02119-0","volume":"402","author":"D Mair","year":"2023","unstructured":"Mair, D., Zaloum, S. A., Patel, F., & Noyce, A. J. (2023). Effectiveness of interactive workshops to raise awareness of the neurological harms associated with nitrous oxide use: A cross-sectional study. Lancet (London England), 402(Suppl 1), S65. https:\/\/doi.org\/10.1016\/S0140-6736(23)02119-0","journal-title":"Lancet (London England)"},{"issue":"10","key":"361_CR12","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1007\/s00115-023-01443-1","volume":"94","author":"JN Mei\u00dfner","year":"2023","unstructured":"Mei\u00dfner, J. N., Hill, K., Lakghomi, A., & Nitsch, L. (2023). Funikul\u00e4re Myelose Und Polyneuropathie durch lachgasinhalation \u2013 eine Differenzialdiagnose Des Guillain-Barr\u00e9-Syndroms [Inhaled nitrous oxide-induced subacute combined degeneration-A differential diagnosis of Guillain-Barr\u00e9 syndrome]. Der Nervenarzt, 94(10), 951\u2013955. https:\/\/doi.org\/10.1007\/s00115-023-01443-1","journal-title":"Der Nervenarzt"},{"key":"361_CR13","doi-asserted-by":"publisher","unstructured":"M\u00e9n\u00e9trier, T., & Denimal, D. (2023). Vitamin B12 status in recreational users of Nitrous Oxide: A systematic review focusing on the prevalence of Laboratory abnormalities. Antioxidants (Basel Switzerland), 12(6). https:\/\/doi.org\/10.3390\/antiox12061191","DOI":"10.3390\/antiox12061191"},{"issue":"1","key":"361_CR14","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1097\/ALN.0b013e318178820b","volume":"109","author":"P Nagele","year":"2008","unstructured":"Nagele, P., Zeugswetter, B., Wiener, C., Burger, H., H\u00fcpfl, M., Mittlb\u00f6ck, M., & F\u00f6dinger, M. (2008). Influence of Methylenetetrahydrofolate Reductase Gene Polymorphisms on homocysteine concentrations after Nitrous Oxide Anesthesia. Anesthesiology, 109(1), 36\u201343. https:\/\/doi.org\/10.1097\/ALN.0b013e318178820b","journal-title":"Anesthesiology"},{"key":"361_CR15","doi-asserted-by":"publisher","unstructured":"Oussalah, A., Julien, M., Levy, J., Hajjar, O., Franczak, C., Stephan, C., Laugel, E., Wandzel, M., Filhine-Tresarrieu, P., Green, R., & Gu\u00e9ant, J. L. (2019). Global Burden related to Nitrous Oxide exposure in Medical and recreational settings: A systematic review and Individual Patient Data Meta-Analysis. Journal of Clinical Medicine, 8(4). https:\/\/doi.org\/10.3390\/jcm8040551","DOI":"10.3390\/jcm8040551"},{"issue":"3","key":"361_CR16","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1136\/pn-2022-003631","volume":"23","author":"A Paris","year":"2023","unstructured":"Paris, A., Lake, L., Joseph, A., Workman, A., Walton, J., Hayton, T., Evangelou, N., Lilleker, J. B., Ayling, R. M., Nicholl, D., & Noyce, A. J. (2023). Nitrous oxide-induced subacute combined degeneration of the cord: Diagnosis and treatment. Practical Neurology, 23(3), 222\u2013228. https:\/\/doi.org\/10.1136\/pn-2022-003631","journal-title":"Practical Neurology"},{"issue":"1","key":"361_CR17","doi-asserted-by":"publisher","first-page":"73","DOI":"10.3390\/brainsci4010073","volume":"4","author":"S Savage","year":"2014","unstructured":"Savage, S., & Ma, D. (2014). The neurotoxicity of Nitrous Oxide: The facts and putative mechanisms. Brain Sciences, 4(1), 73\u201390. https:\/\/doi.org\/10.3390\/brainsci4010073","journal-title":"Brain Sciences"},{"key":"361_CR18","doi-asserted-by":"publisher","first-page":"704","DOI":"10.3389\/fneur.2019.00704","volume":"10","author":"J Tani","year":"2019","unstructured":"Tani, J., Weng, H. Y., Chen, H. J., Chang, T. S., Sung, J. Y., & Lin, C. S. Y. (2019). Elucidating Unique Axonal Dysfunction between Nitrous Oxide abuse and vitamin B12 Deficiency. Frontiers in Neurology, 10, 704. https:\/\/doi.org\/10.3389\/fneur.2019.00704","journal-title":"Frontiers in Neurology"},{"key":"361_CR19","doi-asserted-by":"publisher","unstructured":"Wang, L., Yin, L., Wang, Q., Wang, R., Liu, Z., Dong, M., Duan, X., Zheng, Y., Hong, W., Liu, F., & Tie, C. (2022). SPECT findings on neuropsychiatric symptoms caused by nitrous oxide abuse. Frontiers in Psychiatry, 13., Article 980516. https:\/\/doi.org\/10.3389\/fpsyt.2022.980516","DOI":"10.3389\/fpsyt.2022.980516"},{"issue":"11","key":"361_CR20","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1080\/15563650.2023.2279936","volume":"61","author":"H Wu","year":"2023","unstructured":"Wu, H., Xu, L., Zheng, X., Zhou, X., Zhang, Y., & Sun, Y. (2023). Neuropsychiatric disorders associated with recreational nitrous oxide use. Clinical Toxicology (Philadelphia Pa), 61(11), 961\u2013967. https:\/\/doi.org\/10.1080\/15563650.2023.2279936","journal-title":"Clinical Toxicology (Philadelphia Pa)"},{"issue":"3","key":"361_CR21","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1007\/s12640-021-00352-y","volume":"39","author":"Y Xiang","year":"2021","unstructured":"Xiang, Y., Li, L., Ma, X., Li, S., Xue, Y., Yan, P., Chen, M., & Wu, J. (2021). Recreational nitrous oxide abuse: Prevalence, neurotoxicity, and treatment. Neurotoxicity Research, 39(3), 975\u2013985. https:\/\/doi.org\/10.1007\/s12640-021-00352-y","journal-title":"Neurotoxicity Research"},{"issue":"2","key":"361_CR22","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.bpa.2018.06.003","volume":"32","author":"Z Zafirova","year":"2018","unstructured":"Zafirova, Z., Sheehan, C., & Hosseinian, L. (2018). Update on nitrous oxide and its use in anesthesia practice. Best Practice & Research Clinical Anaesthesiology, 32(2), 113\u2013123. https:\/\/doi.org\/10.1016\/j.bpa.2018.06.003","journal-title":"Best Practice & Research Clinical Anaesthesiology"}],"container-title":["Neurological Research and Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42466-024-00361-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s42466-024-00361-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42466-024-00361-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T17:28:01Z","timestamp":1763141281000},"score":1,"resource":{"primary":{"URL":"https:\/\/neurolrespract.biomedcentral.com\/articles\/10.1186\/s42466-024-00361-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,16]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["361"],"URL":"https:\/\/doi.org\/10.1186\/s42466-024-00361-0","relation":{},"ISSN":["2524-3489"],"issn-type":[{"value":"2524-3489","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,16]]},"assertion":[{"value":"28 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"According to the local ethics committee, University of Bonn, North-Rhine Westphalia, Germany (reference number 2024-358-BO) neither approval of the institutional review board nor patient informed consent were required due to the retrospective character of the analysis of anonymized patient records. All study protocols and procedures were conducted in accordance with the Declaration of Helsinki.","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":"None of the authors declares competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3"}}