Speech-Language Pathology Section, Mark O. Hatfield Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Orphanet J Rare Dis. 2024 Jun 11;19(1):231. doi: 10.1186/s13023-024-03241-7.
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.
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).
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.
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.
尼曼-匹克病 C1 型（NPC1）是一种罕见的溶酶体疾病，具有进行性神经表现，历史上被认为是儿科疾病。然而，人们对成人发病（AO）亚型的认识正在增加，其非特异性症状常导致诊断延迟和误诊。吞咽困难通常被认为是 NPC1 的一种临床发病率，引起对吞咽安全和吸入风险的关注。本研究旨在描述 AO NPC1 的吞咽功能，旨在解决理解和临床管理方面的差距。
在一项前瞻性自然史研究（NCT00344331）中，14 名 AO NPC1 个体接受了全面评估，包括利用 NPC1 严重程度评分量表进行病史和体格检查、视频荧光透视吞咽研究和汇总解释性分析，以及在基线就诊时进行脑脊液（CSF）采集以进行生物标志物评估。采用描述性统计和多变量统计模型分析 NPC1 疾病协变量以及美国言语-语言-听力协会国家结果测量（ASHA-NOMS）和 NIH 渗透吸入量表（NIH-PAS）。
我们的队列由 11 名（78.6%）主要为女性的个体组成，平均年龄为 43.1±16.7 岁。总体而言，我们的 AO 患者能够独立吞咽，无需/仅需最小提示，其中 6 名（43%）避免特定食物或需要更多时间。在进行吸入风险分析时，该队列在 8 名（57%）患者中没有明显的吸入风险或喉吸入，在 5 名（36%）患者中存在间歇性喉穿透和逆行运动的低风险，仅 1 名（7%）患者存在中风险。建议 7 名（50%）患者进行饮食调整，特别是针对液体粘度（n=6，43%）而不是固体（n=3，21%）。吞咽结果与 NPC1 相关参数或 CSF 生物标志物之间未发现显著相关性。
尽管 NPC1 的表现存在异质性，但 AO 队列显示出具有低吸入风险的功能性吞咽能力，一些参与者仍需要进行某种程度的饮食调整。本研究强调了在 AO NPC1 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发病率，例如吸入。这些发现为 AO 队列的评估和管理提供了临床建议，有助于改善这些个体的护理。
