背景:尼曼-皮克病,C1型(NPC1)是一种罕见的溶酶体疾病,具有进行性神经系统表现,历史上被认为是一种儿科疾病。然而,对成人发病(AO)亚型的认识正在增加,常伴有非特异性症状导致延误和误诊。吞咽困难,通常被认为是NPC1的临床发病率,这引起了人们对吞咽安全性和误吸风险的担忧。本研究旨在表征AONPC1的吞咽功能,解决理解和临床管理方面的差距。
方法:在一项前瞻性自然史研究(NCT00344331)中,14名AONPC1个体接受了全面评估,包括使用NPC1严重程度等级量表的病史和体格检查,具有总结解释分析的视频透视吞咽研究,和脑脊液(CSF)收集用于基线访视时的生物标志物评估。采用描述性统计和多元统计模型分析NPC1疾病协变量,以及美国言语-语言-听力协会国家成果测量(ASHA-NOMS)和NIH渗透吸气量表(NIH-PAS)。
结果:我们的队列,由14名主要是女性(n=11,78.6%)组成,初次就诊时平均年龄为43.1±16.7岁。总的来说,我们的AO患者能够独立吞咽,没有/最小的提示,6人(43%)避免特定食物或需要更多时间。根据吸入的风险分析,该队列显示8例(57%)没有明显的误吸风险或喉吸,间歇性喉部穿透和逆行偏移的风险最小5(36%),和中等风险(7%)在只有一个。7(50%)建议进行饮食调整,特别是对于液体粘度(n=6,43%)而不是固体(n=3,21%)。在吞咽结果和NPC1相关参数或CSF生物标志物之间没有发现显著的相关性。
结论:尽管NPC1呈现异质性,AO队列显示功能性吞咽能力,误吸风险较低,部分参与者仍需进行一定程度的饮食调整.这项研究强调了在AONPC1中定期进行吞咽评估和管理的重要性,以解决与吞咽困难相关的潜在疾病,例如误吸。这些发现为AO队列的评估和管理提供了临床建议,有助于改善对这些人的照顾。
BACKGROUND: Niemann-Pick disease, type C1 (NPC1) is a rare lysosomal disorder with progressive neurological manifestations, historically recognized as a pediatric disease. However, awareness of the adult-onset (AO) subtype is increasing, often with non-specific symptoms leading to delayed and misdiagnosis. Dysphagia, commonly recognized as a clinical morbidity in NPC1, raises concerns for swallowing safety and aspiration risk. This study aims to characterize swallowing function in AO NPC1, addressing the gap in understanding and clinical management.
METHODS: Fourteen AO NPC1 individuals in a prospective natural history study (NCT00344331) underwent comprehensive assessments, including history and physical examinations utilizing the NPC1 severity rating scale, videofluoroscopic swallowing studies with summary interpretive analysis, and cerebrospinal fluid (CSF) collection for biomarker evaluation at baseline visit. Descriptive statistics and multivariate statistical modeling were employed to analyze NPC1 disease covariates, along with the American Speech-Language-Hearing Association National Outcome Measure (ASHA-NOMS) and the NIH Penetration Aspiration Scale (NIH-PAS).
RESULTS: Our cohort, comprised of 14 predominately female (n = 11, 78.6%) individuals, had an average age of 43.1 ± 16.7 years at the initial visit. Overall, our AO patients were able to swallow independently with no/minimal cueing, with 6 (43%) avoiding specific food items or requiring more time. Upon risk analysis of aspiration, the cohort demonstrated no obvious aspiration risk or laryngeal aspiration in 8 (57%), minimal risk with intermittent laryngeal penetration and retrograde excursion in 5(36%), and moderate risk (7%) in only one. Dietary modifications were recommended in 7 (50%), particularly for liquid viscosities (n = 6, 43%) rather than solids (n = 3, 21%). No significant correlations were identified between swallowing outcomes and NPC1-related parameters or CSF biomarkers.
CONCLUSIONS: Despite the heterogeneity in NPC1 presentation, the AO cohort displayed functional swallowing abilities with low aspiration risk with some participants still requiring some level of dietary modifications. This study emphasizes the importance of regular swallowing evaluations and management in AO NPC1 to address potential morbidities associated with dysphagia such as aspiration. These findings provide clinical recommendations for the assessment and management of the AO cohort, contributing to improved care for these individuals.