Objective: We aimed to (1) characterise baseline swallow function in people with NPC and (2) evaluate the impact of Miglustat treatment on the swallowing process.

Background: Niemann–Pick disease type C (NPC) is a rare, hereditary neurodegenerative disease, characterised by progressive psychiatric and neurological deficits. Neurological symptoms include cognitive decline and swallowing impairment (dysphagia). Aspiration pneumonia secondary to dysphagia is a leading cause of death in NPC. Miglustat, is currently the only disease-specific treatment shown to be effective in stabilising neurological symptoms. Miglustat has previously been reported to halt or improve early dysphagia symptoms in a paediatric NPC population.

Method: Retrospective analysis of videofluoroscopic swallow studies (VFSS) was completed for ten adults with NPC (mean age 28.44 years ±9.34 years). Participants were recruited through the Royal Melbourne Hospital in Australia between 2008 and 2015. Longitudinal data (range: 12-66 months post-baseline) were available for six participants. All participants in the longitudinal cohort were prescribed Miglustat at a dose of 200mg tds for the duration of the study. Mixed effects regression modelling was applied to data using the Penetration- Aspiration Scale to examine changes in swallowing over time.

Results: Dysphagia was present in 90% of participants at baseline. Reduced lingual function was the most common oral phase impairment and occurred in 50% of participants. The most frequent pharyngeal deficit was a delayed swallowing reflex, observed in 90% of participants across all trialled consistencies. The swallowing reflex was initiated at the base of the valleculae in 60% and the laryngeal aperture in 30% of participants. Swallow impairment was stabilised during Miglustat therapy for periods up to 66 months, with no significant changes in scores (p>0.05).

Conclusion: Findings support the hypothesis that swallowing function does not significantly change for durations of up to 66 months with Miglustat therapy. As dysphagia did not decline nor improve, stabilisation may be the best attainable outcome due to the progressive nature of the disease. Observed characteristics of dysphagia in NPC may be indicative of involvement of the medulla oblongata which controls motor and sensory signals necessary for swallowing. Incorporating VFSS into swallowing screening protocols in NPC may enhance disease management for respiratory and general health.

References: 1. Vanier M. Niemann-Pick disease type C. Orphanet J Rare Dis. 2010. 2. Walterfang M, Chien Y-H, Imrie J, Rushton D, Schubiger D, Patterson MC. Dysphagia as a risk factor for mortality in Niemann-Pick disease type C: systematic literature review and evidence from studies with miglustat. Orphanet Journal of Rare Diseases 2012;7(1):76. 3. Fecarotta S, Amitrano M, Romano A, et al. The videofluoroscopic swallowing study shows a sustained improvement of dysphagia in children with Niemann–Pick disease type C after therapy with miglustat. American Journal of Medical Genetics Part A 2011;155(3):540-547.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dysphagia-in-adults-with-niemann-pick-disease-type-c/