Abstract

Purpose 

To better understand the development of dysphagia in patients with Parkinson disease (PD) and to identify possible neuromodulatory target regions of dysphagia, we studied the striatal dopamine transporter (DAT) availability distribution by subtype of dysphagia.

Methods 

In this retrospective cross-sectional study, patients with PD who underwent videofluoroscopic swallowing study and N-(3-[¹⁸F]fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (¹⁸F-FP-CIT) PET at intervals of less than 1 month were analyzed. The 14 binarized subitem scores of the Videofluoroscopic Dysphagia Scale were analyzed using a voxel-wise Firth’s penalized binary logistic regression model, adjusting for age and disease duration at videofluoroscopic swallowing study.

Results 

Sixty-five patients with PD were finally included. Striatal mapping showed association of decreased DAT availability with 5 subitems with 1 or more clusters surviving the statistical threshold: 1 oral phase and 4 pharyngeal phase subitems. The overlap maps created by superimposing clusters for all 5 statistically significant subitems revealed associations of dysphagia in PD with decreased DAT availability in the bilateral ventral striatum. Of these, 4 subitems belonging to the pharyngeal phase-specific dysphagia were additionally found to be related to dopaminergic degeneration of the bilateral anterior-to-posterior caudate and ventral striatum.

Conclusions 

These findings suggest that subitem/phase-specific striatal subregional dopaminergic depletion may explain the dysphagia of PD. This dopaminergic degeneration of striatal subregions specific to the phases of dysphagia may serve as a potential target for neuromodulatory brain stimulation through stimulation of cortices functionally connected.

Gastrointestinal system disorders are common dysfunctions in Parkinson disease (PD) and are important factors for reduced quality of life and increased mortality.¹ Of these, dysphagia can cause malnutrition and aspiration pneumonia, posing a serious threat to health and maintenance of life, and up to 90% of patients with PD eventually develop dysphagia.²

Experiments using task-specific functional MRI and PET have shown that the swallowing process in human recruits the cerebellum, thalamus, insula, lateral precentral and postcentral gyri, superior temporal gyrus, middle and inferior frontal gyri, frontal operculum, occipital gyrus, precuneus, and anterior cingulate gyrus.^3,4 Furthermore, lesions in areas other than the neuroanatomical area of the brain involved in the normal swallowing process can also cause dysphagia, and in the case of dysphagia in stroke, lesions of putamen and globus pallidus have already been reported to induce dysphagia.^5,6

In PD, nigrostriatal dopaminergic degeneration is a hallmark of its pathogenesis, and many motor and nonmotor symptoms related thereto have been described using functional neuroimaging⁷; however, despite the significant debilitating effects of dysphagia in patients with PD, the relationship between the striatal distribution of dopaminergic loss and dysphagia has not yet been elucidated. When the distribution of dopaminergic degeneration related to each subitem of dysphagia in PD is identified, the indirect effects of targeted transcranial stimulation on dysphagia symptoms can be tested through stimulating functionally connected cortical area, similar to that of noninvasive neuromodulatory stimulation targeted to other motor symptoms in PD.⁸

In the present study, we hypothesized that there may be distributions of striatal dopaminergic degeneration specific to each dysphagia phase. We, therefore, implemented a case-control analyses of the distribution of striatal dopamine transporter (DAT) availability and the clinical parameters indicative of phase-specific dysphagia.

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