{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:06:18Z","timestamp":1791396378769,"version":"4.3.3"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T00:00:00Z","timestamp":1720224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T00:00:00Z","timestamp":1720224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["LU 336\/15-1"],"award-info":[{"award-number":["LU 336\/15-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008977","name":"Universit\u00e4t Ulm","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008977","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Neuroanatomical staging of sporadic amyotrophic lateral sclerosis (ALS) indicates that neurodegeneration may spread corticofugally.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We conducted an observational study to define the initial sites of disease onset and the clinical progression (\u2018spreading patterns\u2019) of motor deficits in a cohort of 910 ALS patients in Germany.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Mean age of ALS onset was 59.0\u2009\u00b1\u200912.6\u00a0years for males and 61.2\u2009\u00b1\u200910.5\u00a0years for females, the mean ALSFRS-R was 35.1\u2009\u00b1\u20099.2, and 7.7% of the cohort reported a family history. Onset of motor symptoms was bulbar\/upper limb in 26.8%\/35.9%, the right arm initially being slightly more often affected than the left (18.5% vs.16.3%). Testing on concordance of handedness and onset in the dominant arm did not reach significance. Lower limb onset was observed in 37.3%. Unilateral limb onset patients reported horizontal spreading about three times more often than vertical spreading. 71\/244 bulbar onset patients reported spreading pattern to the legs, and 17\/339 lumbar onset patients reported spreading secondarily to the bulbar region.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>Our results indicate that, although the phenotype of so-called \u2018spinal\u2019 or \u2018intraspinal\u2019 spreading predominated, we also observed an additional clinical spreading pattern: 29.1% of patients with bulbar onset experienced spreading clinically to the legs (vice versa in 5.0% of lumbar onset patients). For obvious neuroanatomical reasons, this pattern hardly can be explained solely by a \u2018spinal\u2019 or an \u2018intraspinal\u2019 pattern of spreading. Instead, these findings complement insights from previous clinical and clinicopathological studies supporting a cortical initiation of ALS.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-024-12408-y","type":"journal-article","created":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T14:01:39Z","timestamp":1720274499000},"page":"5357-5367","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clinical spreading of muscle weakness in amyotrophic lateral sclerosis (ALS): a study in 910 patients"],"prefix":"10.1007","volume":"271","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5401-0904","authenticated-orcid":false,"given":"Albert C.","family":"Ludolph","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Dietrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Dreyhaupt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Kassubek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Del Tredici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Rosenbohm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,6]]},"reference":[{"issue":"7468","key":"12408_CR1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/nature12481","volume":"501","author":"M Jucker","year":"2013","unstructured":"Jucker M, Walker LC (2013) Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501(7468):45\u201351. https:\/\/doi.org\/10.1038\/nature12481","journal-title":"Nature"},{"issue":"4","key":"12408_CR2","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/BF00308809","volume":"82","author":"H Braak","year":"1991","unstructured":"Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 82(4):239\u2013259. https:\/\/doi.org\/10.1007\/BF00308809","journal-title":"Acta Neuropathol"},{"issue":"Pt 10","key":"12408_CR3","doi-asserted-by":"publisher","first-page":"2814","DOI":"10.1093\/brain\/awv236","volume":"138","author":"H Braak","year":"2015","unstructured":"Braak H, Del Tredici K (2015) The preclinical phase of the pathological process underlying sporadic Alzheimer\u2019s disease. Brain 138(Pt 10):2814\u20132833. https:\/\/doi.org\/10.1093\/brain\/awv236","journal-title":"Brain"},{"issue":"2","key":"12408_CR4","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/s0197-4580(02)00065-9","volume":"24","author":"H Braak","year":"2003","unstructured":"Braak H, Del Tredici K, R\u00fcb U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson\u2019s disease. Neurobiol Aging 24(2):197\u2013211. https:\/\/doi.org\/10.1016\/s0197-4580(02)00065-9","journal-title":"Neurobiol Aging"},{"key":"12408_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-540-89711-4","volume":"201","author":"H Braak","year":"2009","unstructured":"Braak H, Del Tredici K (2009) Neuroanatomy and pathology of sporadic Parkinson\u2019s disease. Adv Anat Embryol Cell Biol 201:1\u2013119. https:\/\/doi.org\/10.1007\/978-3-540-89711-4","journal-title":"Adv Anat Embryol Cell Biol"},{"issue":"S1","key":"12408_CR6","doi-asserted-by":"publisher","first-page":"S73","DOI":"10.3233\/JPD-160880","volume":"7","author":"H Braak","year":"2017","unstructured":"Braak H, Del Tredici K (2017) Neuropathological staging of brain pathology in sporadic Parkinson\u2019s disease: Separating the wheat from the chaff. J Parkinsons Dis 7(S1):S73\u2013S87. https:\/\/doi.org\/10.3233\/JPD-160880","journal-title":"J Parkinsons Dis"},{"issue":"5795","key":"12408_CR7","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1126\/science.1130878","volume":"314","author":"M Neumann","year":"2006","unstructured":"Neumann M, Sampathu D, Kwong L, Truax AC, Micsenyi MC, Chou T, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314(5795):130\u2013133. https:\/\/doi.org\/10.1126\/science.1130878","journal-title":"Science"},{"issue":"9","key":"12408_CR8","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/nrneurol.2013.146","volume":"9","author":"H Braak","year":"2013","unstructured":"Braak H, Brettschneider J, Ludolph AC, Lee VM, Trojanowski JQ, Del Tredici K (2013) Amyotrophic lateral sclerosis\u2014a model of corticofugal axonal spread. Nat Rev Neurol 9(9):708\u2013714. https:\/\/doi.org\/10.1038\/nrneurol.2013.146","journal-title":"Nat Rev Neurol"},{"issue":"1","key":"12408_CR9","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s00401-017-1690-z","volume":"133","author":"H Braak","year":"2017","unstructured":"Braak H, Ludolph AC, Neumann M, Ravits J, Del Tredici K (2017) Pathological TDP-43 changes in Betz cells differ from those in bulbar and spinal a-motoneurons in sporadic amyotrophic lateral sclerosis. Acta Neuropathol 133(1):79\u201390. https:\/\/doi.org\/10.1007\/s00401-017-1690-z","journal-title":"Acta Neuropathol"},{"issue":"1","key":"12408_CR10","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1002\/ana.23356","volume":"74","author":"J Brettschneider","year":"2013","unstructured":"Brettschneider J, Del Tredici K, Toledo JB, Robinson JL, Irwin DJ, Grossman M, Suh E, Van Deerlin VM, Wood EM, Baek Y, Kwong L, Lee EB, Elman L, McCluskey LF, Fang L, Feldengut S, Ludolph AC, Lee VM, Braak H, Trojanowski JQ (2013) Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol 74(1):20\u201338. https:\/\/doi.org\/10.1002\/ana.23356","journal-title":"Ann Neurol"},{"issue":"4","key":"12408_CR11","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1007\/s00401-014-1393-1","volume":"128","author":"J Brettschneider","year":"2014","unstructured":"Brettschneider J, Arai K, Del Tredici K, Toledo JB, Robinson JL, Lee EB, Kuwabara S, Shibuya K, Irwin DJ, Fang L, Van Deerlin VM, Elman L, McCluskey LF, Ludolph AC, Lee VM, Braak H, Trojanowski JQ (2014) TDP-43 pathology and neuronal loss in amyotrophic lateral sclerosis spinal cord. Acta Neuropathol 128(4):423\u2013437. https:\/\/doi.org\/10.1007\/s00401-014-1393-1","journal-title":"Acta Neuropathol"},{"key":"12408_CR12","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s40478-015-0017-0","volume":"3","author":"M Fatima","year":"2015","unstructured":"Fatima M, Tan R, Halliday GM, Kril JJ (2015) Spread of pathology in amyotrophic lateral sclerosis: assessment of phosphorylated TDP-43 along axonal pathways. Acta Neuropathol Commun 3:47. https:\/\/doi.org\/10.1186\/s40478-015-0017-0","journal-title":"Acta Neuropathol Commun"},{"issue":"10","key":"12408_CR13","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1212\/01.wnl.0000264385.71583.00","volume":"68","author":"J Ravits","year":"2007","unstructured":"Ravits J, Paul P, Jorg C (2007) Focality of upper and lower motor neuron degeneration at the clinical onset of ALS. Neurology 68(10):1571\u20131575. https:\/\/doi.org\/10.1212\/01.wnl.0000264385.71583.00","journal-title":"Neurology"},{"issue":"10","key":"12408_CR14","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1212\/01.wnl.0000264386.71583.01","volume":"68","author":"J Ravits","year":"2007","unstructured":"Ravits J, Laurie P, Fan Y, Moore DH (2007) Implications of ALS focality: rostral-caudal distribution of lower motor neuron loss postmortem. Neurology 68(10):1576\u20131582. https:\/\/doi.org\/10.1212\/01.wnl.0000264386.71583.01","journal-title":"Neurology"},{"issue":"Pt B","key":"12408_CR15","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.expneurol.2014.01.006","volume":"262","author":"J Ravits","year":"2014","unstructured":"Ravits J (2014) Focality, stochasticity and neuroanatomic propagation in ALS pathogenesis. Exp Neurol 262(Pt B):121\u2013126. https:\/\/doi.org\/10.1016\/j.expneurol.2014.01.006","journal-title":"Exp Neurol"},{"issue":"9","key":"12408_CR16","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1212\/WNL.0b013e3181e72b60","volume":"75","author":"N Filippini","year":"2010","unstructured":"Filippini N, Douaud G, Mackay CE, Knight S, Talbot K, Turner MR (2010) Corpus callosum involvement is a consistent feature of amyotrophic lateral sclerosis. Neurology 75(9):645\u2013652. https:\/\/doi.org\/10.1212\/WNL.0b013e3181e72b60","journal-title":"Neurology"},{"issue":"8","key":"12408_CR17","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1016\/j.clinph.2015.05.004","volume":"126","author":"P Menon","year":"2015","unstructured":"Menon P, Kiernan MC, Vucic S (2015) Cortical hyperexcitability precedes lower motor neuron dysfunction in ALS. Clin Neurophysiol 126(8):1745\u20131751. https:\/\/doi.org\/10.1016\/j.clinph.2015.05.004","journal-title":"Clin Neurophysiol"},{"issue":"2","key":"12408_CR18","doi-asserted-by":"publisher","first-page":"65","DOI":"10.3988\/jcn.2013.9.2.65","volume":"9","author":"JS Bae","year":"2013","unstructured":"Bae JS, Simon NG, Menon P, Vucic S, Kiernan MC (2013) The puzzling case of hyperexcitability in amyotrophic lateral sclerosis. J Clin Neurol 9(2):65\u201374. https:\/\/doi.org\/10.3988\/jcn.2013.9.2.65","journal-title":"J Clin Neurol"},{"issue":"4","key":"12408_CR19","doi-asserted-by":"publisher","first-page":"369","DOI":"10.3109\/17482960903420140","volume":"11","author":"MR Turner","year":"2010","unstructured":"Turner MR, Brockington A, Scaber J, Hollinger H, Marsden R, Shaw PJ, Talbot K (2010) Pattern of spread and prognosis in lower limb-onset ALS. Amyotroph Lateral Scler 11(4):369\u2013373. https:\/\/doi.org\/10.3109\/17482960903420140","journal-title":"Amyotroph Lateral Scler"},{"issue":"10","key":"12408_CR20","doi-asserted-by":"publisher","first-page":"4105","DOI":"10.1093\/brain\/awad129","volume":"146","author":"A Maranzano","year":"2023","unstructured":"Maranzano A, Verde F, Colombo E, Poletti B, Doretti A, Bonetti R, Gagliardi D, Meneri M, Maderna L, Messina S, Corti S, Morelli C, Silani V, Ticozzi N (2023) Regional spreading pattern is associated with clinical phenotype in amyotrophic lateral sclerosis. Brain 3 146(10):4105\u20134116. https:\/\/doi.org\/10.1093\/brain\/awad129","journal-title":"Brain 3"},{"issue":"8","key":"12408_CR21","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1136\/jnnp.2010.208413","volume":"82","author":"MR Turner","year":"2011","unstructured":"Turner MR, Wicks P, Brownstein CA, Massagli MP, Toronjo M, Talbot K, Al-Chalabi A (2011) Concordance between site of onset and limb dominance in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 82(8):853\u2013854. https:\/\/doi.org\/10.1136\/jnnp.2010.208413","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"12408_CR22","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.als.2014.08.001","volume":"2014","author":"BJ Devine","year":"2014","unstructured":"Devine BJ et al (2014) Study of motor asymmetry in ALS indicates an effect of limb dominance on onset and spread of weakness. ALSFTD 2014:481\u2013487. https:\/\/doi.org\/10.1016\/j.als.2014.08.001","journal-title":"ALSFTD"},{"key":"12408_CR23","doi-asserted-by":"publisher","first-page":"3177","DOI":"10.1177\/13524587221093294","volume":"29","author":"T Yang","year":"2022","unstructured":"Yang T, Wei Q, Li C et al (2022) Spatial\u2013temporal pattern of propagation in amyotrophic lateral sclerosis and effect on survival: a cohort study. Eur J Neurol 29:3177\u20133186. https:\/\/doi.org\/10.1177\/13524587221093294","journal-title":"Eur J Neurol"},{"issue":"5","key":"12408_CR24","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1080\/146608200300079536","volume":"1","author":"BR Brooks","year":"2000","unstructured":"Brooks BR, Miller RG, Swash M, Munsat TL, World Federation of Neurology Research Group on Motor Neuron Diseases (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1(5):293\u2013299","journal-title":"Amyotroph Lateral Scler Other Motor Neuron Disord"},{"issue":"1\u20132","key":"12408_CR25","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/S0022-510X(99)00145-9","volume":"169","author":"JM Cedarbaum","year":"1999","unstructured":"Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci 169(1\u20132):13\u201321. https:\/\/doi.org\/10.1016\/S0022-510X(99)00145-9","journal-title":"J Neurol Sci"},{"issue":"8","key":"12408_CR26","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1212\/01.wnl.0000343819.26740.8a","volume":"73","author":"JM Ravits","year":"2009","unstructured":"Ravits JM, La Spada AR (2009) ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration. Neurology 73(8):805\u2013811. https:\/\/doi.org\/10.1212\/01.wnl.0000343819.26740.8a","journal-title":"Neurology"},{"issue":"11","key":"12408_CR27","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1002\/acn3.51098","volume":"7","author":"M Gromicho","year":"2020","unstructured":"Gromicho M, Figueiral M, Uysal H, Grosskreutz J, Kuzma-Kozakiewicz M, Pinto S, Petri S, Madeira S, Swash M, de Carvalho M (2020) Spreading in ALS: The relative impact of upper and lower motor neuron involvement. Ann Clin Transl Neurol 7(11):1181\u20131192. https:\/\/doi.org\/10.1002\/acn3.51098","journal-title":"Ann Clin Transl Neurol"},{"key":"12408_CR28","doi-asserted-by":"publisher","first-page":"872500","DOI":"10.3389\/fneur.2022.872500","volume":"13","author":"H Zhang","year":"2022","unstructured":"Zhang H, Chen L, Tian J, Fan D (2022) Differentiating slowly progressive subtype of lower limb onset ALS from typical ALS depends on the time of disease progression and phenotype. Front Neurol 13:872500. https:\/\/doi.org\/10.3389\/fneur.2022.872500","journal-title":"Front Neurol"},{"issue":"7","key":"12408_CR29","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1136\/jnnp.2011.262770","volume":"83","author":"T Kanouchi","year":"2012","unstructured":"Kanouchi T, Ohkubo T, Yokota T (2012) Can regional spreading of amyotrophic lateral sclerosis motor symptoms be explained by prion-like propagation? J Neurol Neurosurg Psychiatry 83(7):739\u2013745. https:\/\/doi.org\/10.1136\/jnnp.2011.262770","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"7627","key":"12408_CR30","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nature19891","volume":"539","author":"JP Taylor","year":"2016","unstructured":"Taylor JP, Brown RH Jr, Cleveland DW (2016) Decoding ALS: from genes to mechanism. Nature 539(7627):197\u2013206. https:\/\/doi.org\/10.1038\/nature19891","journal-title":"Nature"},{"key":"12408_CR31","doi-asserted-by":"publisher","first-page":"2762","DOI":"10.1016\/j.bbadis.2017.03.010","volume":"6","author":"MA Hanspal","year":"2017","unstructured":"Hanspal MA, Dobson CM, Yerbury JJ, Kumita JR (2017) The relevance of contact-independent cell-to-cell transfer of TDP-43 and SOD1 in amyotrophic lateral sclerosis. Biochim Biophys Acta Mol Basis Dis 6:2762\u20132771. https:\/\/doi.org\/10.1016\/j.bbadis.2017.03.010","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"8","key":"12408_CR32","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1136\/jnnp-2016-314849","volume":"88","author":"A Eisen","year":"2017","unstructured":"Eisen A, Braak H, Del Tredici K, Lemon R, Ludolph A, Kiernan M (2017) Cortical influences that drive sporadic amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 88(8):917\u2013924. https:\/\/doi.org\/10.1136\/jnnp-2016-314849","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"9","key":"12408_CR33","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1136\/jnnp-2019-321271","volume":"91","author":"AC Ludolph","year":"2020","unstructured":"Ludolph AC, Emilian S, Dreyhaupt J, Rosenbohm A, Kraskov A, Lemon RN, Del Tredici K, Braak H (2020) Pattern of paresis in ALS is consistent with the physiology of the corticomotoneuronal projections to different muscle groups. J Neurol Neurosurg Psychiatry 91(9):991\u2013998. https:\/\/doi.org\/10.1136\/jnnp-2019-321271","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"4","key":"12408_CR34","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1002\/ana.25833","volume":"88","author":"T Burg","year":"2020","unstructured":"Burg T, Bichara C, Scekic-Zahirovic J, Fischer M, Stuart-Lopez G, Brunet A, Lefebvre F, Cordero-Erausquin M, Rouaux C (2020) Absence of subcerebral projection neurons is beneficial in a mouse model of amyotrophic lateral sclerosis. Ann Neurol 88(4):688\u2013702. https:\/\/doi.org\/10.1002\/ana.25833","journal-title":"Ann Neurol"},{"issue":"5","key":"12408_CR35","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1111\/ene.15243","volume":"29","author":"A Maranzano","year":"2022","unstructured":"Maranzano A, Poletti B, Solca F, Torre S, Colombo E, Far\u00e9 M, Ferrucci R, Carelli L, Verde F, Morelli C, Silani V, Ticozzi N (2022) Upper motor neuron dysfunction is associated with the presence of behavioural impairment in patients with amyotrophic lateral sclerosis. Eur J Neurol 29(5):1402\u20131409. https:\/\/doi.org\/10.1111\/ene.15243","journal-title":"Eur J Neurol"},{"issue":"5\u20136","key":"12408_CR36","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1080\/21678421.2021.1889000","volume":"22","author":"NJ Thakore","year":"2021","unstructured":"Thakore NJ, Drawert BJ, Lapin BR, Pioro EP (2021) Progressive arm muscle weakness in ALS follows the same sequence regardless of onset site: use of TOMS, a novel analytic method to track limb strength. Amyotroph Lateral Scler Frontotemporal Degener 22(5\u20136):380\u2013387. https:\/\/doi.org\/10.1080\/21678421.2021.1889000","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"issue":"11","key":"12408_CR37","doi-asserted-by":"publisher","first-page":"2430","DOI":"10.1002\/ana.24368","volume":"263","author":"A Rosenbohm","year":"2016","unstructured":"Rosenbohm A, M\u00fcller HP, H\u00fcbers A, Ludolph AC, Kassubek J (2016) Corticoefferent pathways in pure lower motor neuron disease: a diffusion tensor imaging study. J Neurol 263(11):2430\u20132437. https:\/\/doi.org\/10.1002\/ana.24368","journal-title":"J Neurol"},{"issue":"8","key":"12408_CR38","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1093\/brain\/awn085","volume":"131","author":"S Vucic","year":"2008","unstructured":"Vucic S, Nicholson GA, Kiernan MC (2008) Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis. Brain 131(8):1540\u20131550. https:\/\/doi.org\/10.1093\/brain\/awn085","journal-title":"Brain"},{"issue":"5\u20136","key":"12408_CR39","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3109\/21678421.2015.1049183","volume":"16","author":"A Ludolph","year":"2015","unstructured":"Ludolph A, Drory V, Hardiman O, Nakano I, Ravits J, Robberecht W, Shefner J, WFN Research Group On ALS\/MND (2015) A revision of the El Escorial criteria\u20142015. Amyotroph Lateral Scler Frontotemporal Degener 16(5\u20136):291\u2013292. https:\/\/doi.org\/10.3109\/21678421.2015.1049183","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-024-12408-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-024-12408-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-024-12408-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T15:27:46Z","timestamp":1723476466000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-024-12408-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,6]]},"references-count":39,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["12408"],"URL":"https:\/\/doi.org\/10.1007\/s00415-024-12408-y","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,6]]},"assertion":[{"value":"24 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All persons gave their informed consent prior to their inclusion in the study. The study was performed according to the Declaration of Helsinki and approved by the local institutional ethics board (references 11\/10 and 19\/12).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standards"}}]}}