{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:14:29Z","timestamp":1792804469506,"version":"4.5.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in the ADCY5 gene can cause a complex hyperkinetic movement disorder. Episodic exacerbations of dyskinesia are a particularly disturbing symptom as they occur predominantly during night and interrupt sleep. We present the clinical short- and long-term effects of pallidal deep brain stimulation (DBS) in three patients with a confirmed pathogenic ADCY5 mutation. Patients were implanted with bilateral pallidal DBS at the age of 34, 20 and 13\u00a0years. Medical records were reviewed for clinical history. Pre- and postoperative video files were assessed using the \u201cAbnormal Involuntary Movement Scale\u201d (AIMS) as well as the motor part of the \u201cBurke Fahn Marsden Dystonia Rating Scale\u201d (BFMDRS). All patients reported subjective general improvement ranging from 40 to 60%, especially the reduction of nocturnal episodic dyskinesias (80\u201390%). Objective scales revealed only a mild decrease of involuntary movements in all and reduced dystonia in one patient. DBS-induced effects were sustained up to 13\u00a0years after implantation. We demonstrate that treatment with pallidal DBS was effective in reducing nocturnal dyskinetic exacerbations in patients with ADCY5-related movement disorder, which was sustained over the long term.<\/jats:p>","DOI":"10.1007\/s00415-020-09871-8","type":"journal-article","created":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T11:07:44Z","timestamp":1594292864000},"page":"3624-3631","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Deep brain stimulation reduces (nocturnal) dyskinetic exacerbations in patients with ADCY5 mutation: a case series"],"prefix":"10.1007","volume":"267","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3291-7222","authenticated-orcid":false,"given":"Ana Lu\u00edsa","family":"de Almeida Marcelino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0597-2648","authenticated-orcid":false,"given":"Tina","family":"Mainka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9063-0556","authenticated-orcid":false,"given":"Patricia","family":"Krause","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4367-0971","authenticated-orcid":false,"given":"Werner","family":"Poewe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8077-8530","authenticated-orcid":false,"given":"Christos","family":"Ganos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea A.","family":"K\u00fchn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"issue":"7","key":"9871_CR1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/mds.26598","volume":"31","author":"FCF Chang","year":"2016","unstructured":"Chang FCF, Westenberger A, Dale RC et al (2016) Phenotypic insights into ADCY5 -associated disease, vol. 31. Move Dis 31(7):1033\u20131040","journal-title":"Move Dis"},{"issue":"7","key":"9871_CR2","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/mdc3.12816","volume":"6","author":"N Vijiaratnam","year":"2019","unstructured":"Vijiaratnam N, Bhatia KP, Lang AE et al (2019) ADCY5\u2013related dyskinesia: improving clinical detection of an evolving disorder, vol. 6. Move Dis Clin Pract 6(7):512\u2013520","journal-title":"Move Dis Clin Pract"},{"issue":"23","key":"9871_CR3","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1212\/WNL.0000000000002058","volume":"85","author":"DH Chen","year":"2015","unstructured":"Chen DH, M\u00e9neret A, Friedman JR et al (2015) ADCY5-related dyskinesia: broader spectrum and genotype-phenotype correlations, vol 85. Neurology 85(23):2026\u20132035","journal-title":"Neurology"},{"issue":"1","key":"9871_CR4","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/mds.26494","volume":"31","author":"JR Friedman","year":"2016","unstructured":"Friedman JR, M\u00e9neret A, Chen D-H et al (2016) ADCY5 mutation carriers display pleiotropic paroxysmal day and nighttime dyskinesias Vol 31. Move Dis 31(1):147\u2013148","journal-title":"Move Dis"},{"issue":"5","key":"9871_CR5","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1111\/j.1399-0004.1978.tb02146.x","volume":"14","author":"TD Bird","year":"1978","unstructured":"Bird TD, Hall JG (1978) Additional information on familial essential (benign) chorea [Internet]. Clin Genet 14(5):271\u2013272. https:\/\/doi.org\/10.1111\/j.1399-0004.1978.tb02146.x","journal-title":"Clin Genet"},{"issue":"4","key":"9871_CR6","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/ana.98","volume":"49","author":"M Fernandez","year":"2001","unstructured":"Fernandez M, Raskind W, Wolff J et al (2001) Familial dyskinesia and facial myokymia (FDFM): a novel movement disorder, vol 49. Ann Neurol. 49(4):486\u2013492","journal-title":"Ann Neurol."},{"issue":"5","key":"9871_CR7","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1001\/archneurol.2012.54","volume":"69","author":"YZ Chen","year":"2012","unstructured":"Chen YZ, Matsushita MM, Robertson P et al (2012) Autosomal dominant familial dyskinesia and facial myokymia: single exome sequencing identifies a mutation in adenylyl cyclase 5. vol 69. Arch Neurol 69(5):630\u2013635","journal-title":"Arch Neurol"},{"key":"9871_CR8","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.parkreldis.2017.05.004","volume":"41","author":"M Carecchio","year":"2017","unstructured":"Carecchio M, Mencacci NE, Iodice A et al (2017) ADCY5-related movement disorders: Frequency, disease course and phenotypic variability in a cohort of paediatric patients Vol 41. Parkinsonism Related Dis 41:37\u201343","journal-title":"Parkinsonism Related Dis"},{"issue":"19","key":"9871_CR9","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1056\/NEJMoa063618","volume":"355","author":"A Kupsch","year":"2006","unstructured":"Kupsch A, Benecke R, M\u00fcller J et al (2006) Pallidal deep-brain stimulation in primary generalized or segmental dystonia Vol 355. N Engl J Med 355(19):1978\u20131990","journal-title":"N Engl J Med"},{"issue":"12","key":"9871_CR10","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/S1474-4422(12)70257-0","volume":"11","author":"J Volkmann","year":"2012","unstructured":"Volkmann J, Wolters A, Kupsch A et al (2012) Pallidal deep brain stimulation in patients with primary generalised or segmental dystonia: 5-year follow-up of a randomised trial Vol 11. Lancet Neurol. 11(12):1029\u20131038","journal-title":"Lancet Neurol."},{"key":"9871_CR11","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.parkreldis.2018.02.030","volume":"51","author":"S Zittel","year":"2018","unstructured":"Zittel S, Tadic V, Moll CKE et al (2018) Prospective evaluation of Globus pallidus internus deep brain stimulation in Huntington\u2019s disease, vol 51. Parkinsonism Related Dis 51:96\u2013100","journal-title":"Parkinsonism Related Dis"},{"issue":"10","key":"9871_CR12","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1007\/s00702-014-1201-7","volume":"121","author":"D Gruber","year":"2014","unstructured":"Gruber D, Kuhn AA, Schoenecker T et al (2014) Quadruple deep brain stimulation in Huntington\u2019s disease, targeting pallidum and subthalamic nucleus: case report and review of the literature vol 121. J Neural Trans (Vienna Aus 1996) 121(10):1303\u20131312","journal-title":"J Neural Trans (Vienna Aus 1996)"},{"issue":"8","key":"9871_CR13","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1177\/0883073816635749","volume":"31","author":"ME Dy","year":"2016","unstructured":"Dy ME, Chang FCF, De Jesus S et al (2016) Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation: A Multicenter Case Series Vol 31. J Child Neurol. 31(8):1027\u20131035","journal-title":"J Child Neurol."},{"issue":"4","key":"9871_CR14","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1177\/0883073816681353","volume":"32","author":"IA Meijer","year":"2017","unstructured":"Meijer IA, Miravite J, Kopell BH et al (2017) Deep brain stimulation in an additional patient With ADCY5-related movement disorder vol 32. J Child Neurol 32(4):438\u2013439","journal-title":"J Child Neurol"},{"issue":"7","key":"9871_CR15","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.5664\/jcsm.7886","volume":"15","author":"A M\u00e9neret","year":"2019","unstructured":"M\u00e9neret A, Roze E, Maranci JB et al (2019) Sleep in ADCY5-related dyskinesia: prolonged awakenings caused by abnormal movements, vol 15. J Clin Sleep Med 15(7):1021\u20131029","journal-title":"J Clin Sleep Med"},{"issue":"12","key":"9871_CR16","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.tins.2012.07.001","volume":"35","author":"M Lazarus","year":"2012","unstructured":"Lazarus M, Huang ZL, Lu J, Urade Y, Chen JF (2012) How do the basal ganglia regulate sleep-wake behavior? Trends in neurosciences. Elsevier Curr Trends 35(12):723\u2013732. https:\/\/doi.org\/10.1016\/j.tins.2012.07.001","journal-title":"Elsevier Curr Trends"},{"issue":"1","key":"9871_CR17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-017-02088-w","volume":"9","author":"YJ Luo","year":"2018","unstructured":"Luo YJ, Li YD, Wang L et al (2018) Nucleus accumbens controls wakefulness by a subpopulation of neurons expressing dopamine D1 receptors, vol 9. Nat Commun 9(1):1\u201317","journal-title":"Nat Commun"},{"issue":"4","key":"9871_CR18","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1002\/ana.24119","volume":"75","author":"Y-Z Chen","year":"2014","unstructured":"Chen Y-Z, Friedman JR, Chen D-H et al (2014) Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia, vol 75. Ann Neurol 75(4):542\u2013549","journal-title":"Ann Neurol"},{"issue":"27","key":"9871_CR19","doi-asserted-by":"crossref","first-page":"10067","DOI":"10.1523\/JNEUROSCI.6730-10.2011","volume":"31","author":"M Lazarus","year":"2011","unstructured":"Lazarus M, Shen HY, Cherasse Y et al (2011) Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens, vol 31. J Neurosci 31(27):10067\u201310075","journal-title":"J Neurosci"},{"issue":"6","key":"9871_CR20","doi-asserted-by":"publisher","first-page":"439","DOI":"10.7326\/L19-0038","volume":"171","author":"A M\u00e9neret","year":"2019","unstructured":"M\u00e9neret A, Gras D, McGovern E, Roze E (2019) Caffeine and the dyskinesia related to mutations in the ADCY5 gene. Ann Intern Med Am Coll Phys 171(6):439. https:\/\/doi.org\/10.7326\/L19-0038","journal-title":"Ann Intern Med Am Coll Phys"},{"issue":"3","key":"9871_CR21","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/j.1460-9568.2009.07062.x","volume":"31","author":"MH Qiu","year":"2010","unstructured":"Qiu MH, Vetrivelan R, Fuller PM et al (2010) Basal ganglia control of sleep-wake behavior and cortical activation, vol 31. Eur J Neurosci. 31(3):499\u2013507","journal-title":"Eur J Neurosci."},{"key":"9871_CR22","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.neuroscience.2016.02.032","volume":"13","author":"MH Qiu","year":"2016","unstructured":"Qiu MH, Chen MC, Wu J, Nelson D, Lu J (2016) Deep brain stimulation in the globus pallidus externa promotes sleep. Neuroscience 322:115\u2013120. https:\/\/doi.org\/10.1016\/j.neuroscience.2016.02.032","journal-title":"Neuroscience"},{"key":"9871_CR23","doi-asserted-by":"crossref","unstructured":"Castillo PR, Middlebrooks EH, Grewal SS, et al (2020) Globus pallidus externus deep brain stimulation treats insomnia in a patient with parkinson disease. In: Mayo Clinic Proceedings. Elsevier Ltd, pp 419\u201322","DOI":"10.1016\/j.mayocp.2019.11.020"},{"issue":"AUG","key":"9871_CR24","doi-asserted-by":"crossref","first-page":"697","DOI":"10.3389\/fneur.2018.00697","volume":"9","author":"VD Sharma","year":"2018","unstructured":"Sharma VD, Sengupta S, Chitnis S et al (2018) Deep brain stimulation and sleep-wake disturbances in parkinson disease: a review, vol 9. Front Neurol 9(AUG):697","journal-title":"Front Neurol"},{"issue":"5","key":"9871_CR25","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1056\/NEJMoa042187","volume":"352","author":"M Vidailhet","year":"2005","unstructured":"Vidailhet M, Vercueil L, Houeto J-L et al (2005) Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia, vol 352. N Engl J Med 352(5):459\u2013467","journal-title":"N Engl J Med"},{"issue":"6","key":"9871_CR26","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1212\/01.wnl.0000252932.71306.89","volume":"68","author":"SW Hung","year":"2007","unstructured":"Hung SW, Hamani C, Lozano AM et al (2007) Long-term outcome of bilateral pallidal deep brain stimulation for primary cervical dystonia, vol 68. Neurology 68(6):457\u2013459","journal-title":"Neurology"},{"key":"9871_CR27","first-page":"1","volume":"13","author":"P Krause","year":"2020","unstructured":"Krause P, V\u00f6lzmann S, Ewert S et al (2020) Long-term effects of bilateral pallidal deep brain stimulation in dystonia: a follow-up between 8 and 16 years. J Neurol 13:1\u201310","journal-title":"J Neurol"},{"issue":"6","key":"9871_CR28","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1002\/mds.26129","volume":"30","author":"R Erro","year":"2015","unstructured":"Erro R, Hersheson J, Ganos C et al (2015) H-ABC syndrome and DYT4: Variable expressivity or pleiotropy of TUBB4 mutations? Vol 30. Move Dis 30(6):828\u2013833","journal-title":"Move Dis"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-020-09871-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-020-09871-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-020-09871-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T23:34:26Z","timestamp":1625787266000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-020-09871-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,9]]},"references-count":28,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["9871"],"URL":"https:\/\/doi.org\/10.1007\/s00415-020-09871-8","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,9]]},"assertion":[{"value":"8 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 April 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"There are no conflicts of interest to declare regarding funding\/sponsoring of this manuscript from any of the authors. Independently from the submitted work: ALAM has no conflicts of interest to declare. TM receives royalties from Urban Fischer in Elsevier Verlag. TM is a participant in the BIH-Charite\u0301 Clinician Scientist Program funded by the Charite\u0301-Universit\u00e4tsmedizin Berlin and the Berlin Institute of Health. PK received speaker\u00b4s honoraria from Medtronic. WP reports personal fees from AbbVie, Affiris, AstraZeneca, BIAL, Boston Scientific, Britannia, Intec, Ipsen, Lundbeck, Neuroderm, Neurocrine, Denali Pharmaceuticals, Novartis, Orion Pharma, Prexton,Teva, UCB and Zambon (consultancy and lecture fees in relation to clinical drug development programmes for PD). WP has Royalties in Thieme, Wiley Blackwell, Oxford University Press and Cambridge University Press and has received grant support from MJFF; EU FP7 & Horizon 2020. CG holds a research grant from the VolkswagenStiftung (Freigeist Fellowship), and was supported by the German Parkinson Society, the Deutsche Forschungsgemeinschaft (DFG; GA2031\/1\u20131 and GA2031\/1\u20132) and Actelion Pharmaceuticals. AAK declares that she is on the advisory board of Boston Scientific and Medtronic and has received honoraria from Boston Scientific, Medtronic, Abbott, Teva und Ipsen.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"This manuscript does not contain clinical studies, thus no ethics approval was necessary.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"This manuscript does not contain clinical studies.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All patients provided written informed consent for publication.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}