{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:59:19Z","timestamp":1790261959292,"version":"4.1.0"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"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":["BMC Neurol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Compared with typical bulbar onset amyotrophic lateral sclerosis (ALS), isolated bulbar palsy (IBP), an often under-understood variant of ALS, is characterized by symptoms confined to bulbar region for extended periods and relative preservation of limb and ventilation function. To find a cutoff value of disease duration that can distinguish IBP from typical bulbar onset ALS well, the association of survival with disease progression in bulbar onset ALS patients was analyzed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Clinical data of bulbar onset ALS patients were collected from January 2009 to December 2013. The duration from bulbar onset to first significant limb involvement was analyzed by a cutoff point analysis with maximally selected log-rank statistics and dichotomized to categorize patient outcomes. The patients were divided into two groups, the IBP and typical bulbar onset ALS groups, according to the cutoff value. Clinical features were compared.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>115 bulbar onset ALS patients were recruited, and the duration from bulbar onset to first significant limb involvement was associated with survival (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). The cutoff duration was 20\u2009months. 19 patients were identified as IBP and 96 patients as typical bulbar onset ALS using 20\u2009months as the cutoff duration. Female was more common, limb weakness was less frequent and pure upper motor neuron (UMN) bulbar signs were more frequent in the IBP group than in the typical bulbar onset ALS group (<jats:italic>P<\/jats:italic>\u2009=\u20090.047; <jats:italic>P<\/jats:italic>\u2009=\u20090.004; <jats:italic>P<\/jats:italic>\u2009=\u20090.031). The median survival time of the IBP group was significantly longer than that of the typical bulbar onset ALS group (64\u2009months and 26\u2009months, respectively; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>A cutoff duration of 20\u2009months from bulbar onset to first significant limb involvement may be used to specifically distinguish IBP from typical bulbar onset ALS. IBP was characterized by female predominance, relative preservation of limb function, more pure UMN bulbar signs and a relatively benign prognosis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12883-021-02438-8","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T11:03:42Z","timestamp":1634900622000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Disease duration of progression is helpful in identifying isolated bulbar palsy of amyotrophic lateral sclerosis"],"prefix":"10.1186","volume":"21","author":[{"given":"Huagang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhou","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"2438_CR1","doi-asserted-by":"publisher","first-page":"17071","DOI":"10.1038\/nrdp.2017.71","volume":"3","author":"O Hardiman","year":"2017","unstructured":"Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, et al. Amyotrophic lateral sclerosis. Nat Rev Dis Primers. 2017;3:17071.","journal-title":"Nat Rev Dis Primers"},{"key":"2438_CR2","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1056\/NEJMra1603471","volume":"377","author":"RH Brown","year":"2017","unstructured":"Brown RH, Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med. 2017;377:162\u201372.","journal-title":"N Engl J Med"},{"key":"2438_CR3","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1136\/jnnp.2010.235952","volume":"82","author":"A Chi\u00f2","year":"2011","unstructured":"Chi\u00f2 A, Calvo A, Moglia C, Mazzini L, Mora G, PARALS study group. Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry. 2011;82:740\u20136.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2438_CR4","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1136\/jnnp-2015-310471","volume":"86","author":"L Chen","year":"2015","unstructured":"Chen L, Zhang B, Chen R, Tang L, Liu R, Yang Y, et al. Natural history and clinical features of sporadic amyotrophic lateral sclerosis in China. J Neurol Neurosurg Psychiatry. 2015;86:1075\u201381.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2438_CR5","doi-asserted-by":"publisher","first-page":"283","DOI":"10.3109\/17482968.2011.551940","volume":"12","author":"JR Burrell","year":"2011","unstructured":"Burrell JR, Vucic S, Kiernan MC. Isolated bulbar phenotype of amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2011;12:283\u20139.","journal-title":"Amyotroph Lateral Scler"},{"key":"2438_CR6","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.ncl.2015.07.003","volume":"33","author":"O Jawdat","year":"2015","unstructured":"Jawdat O, Statland JM, Barohn RJ, Katz JS, Dimachkie MM. Amyotrophic lateral sclerosis regional variants (brachial amyotrophic diplegia, leg amyotrophic diplegia, and isolated bulbar amyotrophic lateral sclerosis). Neurol Clin. 2015;33:775\u201385.","journal-title":"Neurol Clin"},{"key":"2438_CR7","first-page":"293","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. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2000;1:293\u20139.","journal-title":"Amyotroph Lateral Scler"},{"key":"2438_CR8","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1007\/s00415-018-8968-7","volume":"266","author":"M Breza","year":"2019","unstructured":"Breza M, Koutsis G. Kennedy's disease (spinal and bulbar muscular atrophy): a clinically oriented review of a rare disease. J Neurol. 2019;266:565\u201373.","journal-title":"J Neurol"},{"key":"2438_CR9","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1164\/rccm.201510-1966ST","volume":"192","author":"CL Rochester","year":"2015","unstructured":"Rochester CL, Vogiatzis I, Holland AE, Lareau SC, Marciniuk DD, Puhan MA, et al. An Official American Thoracic Society\/European Respiratory Society Policy Statement: Enhancing Implementation, Use, and Delivery of Pulmonary Rehabilitation. Am J Respir Crit Care Med. 2015;192:1373\u201386.","journal-title":"Am J Respir Crit Care Med"},{"key":"2438_CR10","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S0167-9473(02)00225-6","volume":"43","author":"T Hothorn","year":"2003","unstructured":"Hothorn T, Lausen B. On the exact distribution of maximally selected rank statistics. Comput Stat Data Anal. 2003;43:121\u201337.","journal-title":"Comput Stat Data Anal"},{"key":"2438_CR11","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.4103\/0366-6999.211538","volume":"1300","author":"HG Zhang","year":"2017","unstructured":"Zhang HG, Chen L, Tang L, Zhang N, Fan DS. Clinical features of isolated bulbar palsy of amyotrophic lateral sclerosis in Chinese population. Chin Med J. 2017;1300:1768\u201372.","journal-title":"Chin Med J"},{"key":"2438_CR12","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1111\/neup.12606","volume":"40","author":"T Takeda","year":"2020","unstructured":"Takeda T, Kitagawa K, Arai K. Phenotypic variability and its pathological basis in amyotrophic lateral sclerosis. Neuropathology. 2020;40:40\u201356.","journal-title":"Neuropathology"},{"key":"2438_CR13","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, et al. Spreading in ALS: the relative impact of upper and lower motor neuron involvement. Ann Clin Transl Neurol. 2020;7:1181\u201392.","journal-title":"Ann Clin Transl Neurol"}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-021-02438-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12883-021-02438-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-021-02438-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T11:12:06Z","timestamp":1634901126000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/s12883-021-02438-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,22]]},"references-count":13,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2438"],"URL":"https:\/\/doi.org\/10.1186\/s12883-021-02438-8","relation":{},"ISSN":["1471-2377"],"issn-type":[{"value":"1471-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,22]]},"assertion":[{"value":"18 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 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":"This study was approved by the Ethical Committee of Peking University Third Hospital (PUTH) (No. 2008009) according to the declaration of Helsinki. Informed consent was obtained from all patients prior to their inclusion in the study.","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":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"405"}}