Swallowing characterization of adult-onset Niemann-Pick, type C1 patients

Abstract

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.

Conclusion: 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.

Fig. 1

Frequency of swallowing outcome scores of adult-onset cohort at baseline visit. *These swallowing outcomes scales were reversed and transformed to make them consistent with the direction of all rating scales used in the analysis. For all scales utilized, a score of 0 signifies safe independent swallowing function, no aspiration risk, normal (no dysphagia), or no dietary modifications. ASHA-NOMS, American Speech-Hearing Association National Outcomes Measure Score; NIH-PAS, National Institutes of Health Aspiration and Penetration Score; NSS, Neurological Severity Scale

Fig. 2

Frequency of NPC1 Neurological Severity Score (NSS) major domain scores for adult-onset NPC1 patients at baseline visit. For NSS major domains, a score of 0 indicates normal functioning, with severity increasing as the score rises. Detailed descriptions of scores for each domain can be found in the NSS Clinical Severity Scale outlined by Yanjanin et al. [28]. NSS, Neurological Severity Scale

Fig. 3

Frequency of NPC1 Neurological Severity Score (NSS) modifier domain scores for adult-onset NPC1 patients at baseline visit. For NSS modifier domains, a score of 0 indicates normal functioning, with severity increasing as the score rises. Detailed descriptions of scores for each domain can be found in the NSS Clinical Severity Scale outlined by Yanjanin et al. [28]. NSS, Neurological Severity Scale