Brainstem Ventilatory Dysfunction: A Plausible Mechanism for Dyspnea in Parkinson's Disease?

Abstract

Dyspnea is an under‐recognized and debilitating symptom that is reported in up to 40% of patients with Parkinson's disease and may have multiple origins. Despite its frequency, it is poorly researched, and there is a general lack of understanding of the pathophysiology of dyspnea and respiratory dysfunction in PD. Consequently, a number of PD patients are labelled as having “unexplained dyspnea.” Studies to date have focused mainly on evaluating ventilatory capacity and lung volumes, and little is known about the effects of the disease on the medullary and pontine ventilatory control centers within the brainstem. This is of particular relevance in view of neuropathological studies demonstrating early involvement of the dorsal medulla and other brainstem structures by the disease process. The possibility that impaired brainstem ventilatory control is a contributory mechanism for dyspnea and could be a premotor manifestation in some PD patients therefore warrants further attention. This review focuses on clinical, pathological, and experimental evidence for the involvement of brainstem respiratory centers in PD. We highlight the need for further research, particularly in PD patients with unexplained dyspnea. © 2020 International Parkinson and Movement Disorder Society

A 12-month, dose-level blinded safety and efficacy study of levodopa inhalation powder (CVT-301, Inbrija) in patients with Parkinson's disease

“…This suggests that decline in pulmonary function approached clinical significance. However, the earlier study [7] showed a similar decline in FEV 1 and DL CO in the observational group, suggesting that pulmonary decline is related to PD progression rather than CVT-301 inhalation [23]. The mean number of doses taken per day during the present study was about 2.…”

Hypoxia Conditioning as a Promising Therapeutic Target in Parkinson's Disease?

“…6 Accumulating evidence attributes important roles of oxygen availability to α-synuclein pathology initiation and progression. Ventilatory dysfunction is indeed a common but underrecognized and underinvestigated symptom in PD 7 and other α-synucleinopathies. 8 Already more than 20 years ago, Serebrovskaya and colleagues 9 reported impaired hypoxic ventilatory responses in PD-patients.…”

Effects of COVID‐19 on Parkinson's Disease Clinical Features: A Community‐Based Case‐Control Study

“…[6][7][8][9] Patients with PD are frailer than the general population because of disease-related factors and agerelated comorbidities. [2][3][4]10,11 A higher COVID-19 mortality rate has been described in advanced PD patients in association with older age and longer disease duration. 12 Our primary objective was to investigate the effects of COVID-19 on motor and nonmotor symptoms in a community-based PD cohort.…”

“…COVID‐19 may worsen PD by a number of mechanisms, 2‐4 including pharmacodynamics changes (eg, reciprocal interactions between the dopaminergic and renin‐angiotensin systems in the substantia nigra and striatum 5 ) as well as systemic inflammatory responses 6‐9 . Patients with PD are frailer than the general population because of disease‐related factors and age‐related comorbidities 2‐4,10,11 . A higher COVID‐19 mortality rate has been described in advanced PD patients in association with older age and longer disease duration 12 …”