Unravelling the neural network of breathing in myotonic dystrophy: an exploratory study

Rationale: Myotonic dystrophy type I is a neuromuscular disease and the most common form of muscular dystrophy in adults. Patients with myotonic dystrophy commonly experience significant breathing problems that can lead to respiratory failure or require mechanical ventilation. Moreover, respiratory failure is the leading cause of death in myotonic dystrophy. However, the exact pathophysiology of respiratory failure in myotonic dystrophy is unknown. The complex process of neural control of breathing may be involved, but is understudied. In part, this is caused by methodological limitations to assess breathing related cerebral activity. In this study, we will test the feasibility of advanced techniques (functional MRI and respiratory (electro)physiological techniques) to measure breathing-task related cerebral activity and perform a pilot study to test the hypothesis that the functional architecture of the cerebral network controlling breathing is impaired in patients with myotonic dystrophy type I. More specifically, we expect that patients with myotonic dystrophy show reduced breathing-task related cerebral activity in response to respiratory stimuli compared to healthy subjects.

Objective: Phase 1. Primary Objective: To evaluate the feasibility of the study procedures to measure breathing-task related cerebral activity using fMRI and respiratory (electro)physiological measures of breathing. Phase 2. Primary Objective: To identify disease (myotonic dystrophy) specific alterations in breathing-task related cerebral activity. Secondary Objective: To explore the relation between fMRI measures and respiratory (electro)physiological measures of cerebral breathing activity.
Study design: Exploratory cross-sectional study.

Study population: Healthy subjects (n=30) and patients with myotonic dystrophy (n=20) >18 year.

Main study parameters/endpoints: Breathing-task related cerebral activity as a function of breathing condition (rest, paced and loaded) and disease (with or without myotonic dystrophy).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risk of this study for the participants is negligible. Subjects do not directly benefit from participating in this study. The scientific benefit of this study is to achieve a better understanding of the neural control of breathing in myotonic dystrophy. The outcomes of this study may give rise to future new treatments for myotonic dystrophy. The burden of the separate study procedures are relatively small: there are no invasive procedures. However, the total time of the visit and the collective burden of the experiments may be perceived as strenuous.

The functional architecture of the cerebral network controlling breathing is impaired in patients with myotonic dystrophy type I.

- T0: primary and secondary outcome parameters will be obtained one time during a one-day visit.

An overview of the different outcome parameters and their respective method is given in the 'Primary outcome' and 'Secondary outcome' fields.

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