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Aspiration may be clinically apparent or silent, reflecting impaired airway sensation and protective reflexes. We aimed to characterize aspiration and silent aspiration in the National Institutes of Health (NIH) NPC1 Natural History Study (NCT00344331). We analyzed 130 participants with NPC1 enrolled between 2006 and 2024 who underwent speech-language pathology swallowing evaluations, including clinically indicated videofluoroscopic swallow studies (VFSS). Aspiration risk was rated using the NIH Penetration\u2013Aspiration Scale (NIH-PAS). Silent aspiration was defined as aspiration on VFSS without cough, throat clearing, or wet vocal quality. Longitudinal models examined the presence of silent aspiration alone or (2) a NIH-PAS score &gt; 1 (moderate\u2013profound aspiration) or silent aspiration. Covariates included demographics, neurologic disease onset and duration, body weight\/BMI, reflux and seizure medications, miglustat use, NPC Neurological Severity Score (NSS) 5-domain total and subscores (including swallow and respiratory), and the Annualized Severity Increment Score (ASIS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Silent aspiration occurred in 24\/130 (18.4%) participants. Among these, 50% demonstrated recurrent silent aspiration at subsequent visits, and 58.3% exhibited intermittent silent aspiration on follow-up. Considering aspiration risk, 27\/130 (20.8%) had NIH-PAS\u2009&gt;\u20091, including all silent aspirators. Silent aspiratiors alone had worse NIH-PAS, higher total NSS with poorer swallow, speech, ambulation, and fine-motor subscores, and higher ASIS. Patients with silent aspiration or NIH-PAS\u2009&gt;\u20091 had an increased aspiration risk with longer neurologic symptom duration, seizure history, higher NSS, higher ASIS, and in children with lower weight percentile. Miglustat use was protective in the overall cohort, but not in the pediatric subgroup (&lt;\u200920 years-old). Mean time to silent aspiration was ~\u200910 years from neurologic symptom onset, with no difference by neurological disease onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Silent aspiration is common in NPC1 and closely linked to advancing neurologic disease severity than to age-of-onset phenotype. Bedside clinical evaluations may underestimate silent aspiration; proactive longitudinal swallowing surveillance is warranted in individuals with higher NSS\/ASIS scores, seizure history, pediatric weight decline, or evolving motor-speech impairment. These findings support incorporating overt and silent aspiration alongside swallowing function, into routine care and therapeutic trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-026-04543-8","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T14:57:13Z","timestamp":1787410633000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aspiration and silent aspiration in Niemann-Pick disease type C1: longitudinal findings from the NIH natural history study"],"prefix":"10.1186","volume":"21","author":[{"given":"Beth I.","family":"Solomon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Munoz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiden","family":"Borruso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninet","family":"Sinaii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Farhat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desiree A.","family":"Labor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An Dang","family":"Do","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Forbes D.","family":"Porter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"issue":"1","key":"4543_CR1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/gim.2015.25","volume":"18","author":"CA Wassif","year":"2016","unstructured":"Wassif CA, Cross JL, Iben J, Sanchez-Pulido L, Cougnoux A, Platt FM, et al. 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The contributions of the NIH author(s) are considered Works of the United States Government. The findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients provided informed consent\/assent and were enrolled under an NIH-IRB approved study. Ethical approval was initially provided by the NICHD IRB, and ongoing ethical approval is provided by the NIH Clinical Center IRB. All procedures were performed in accordance with the ethical standards of these institutional committees and the Declaration of Helsinki.","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"312"}}