Respiratory assessment in centronuclear myopathies

Abstract

The centronuclear myopathies (CNMs) are a group of inherited neuromuscular disorders classified as congenital myopathies. While several causative genes have been identified, some patients do not harbor any of the currently known mutations. These diverse disorders have common histological features, which include a high proportion of centrally nucleated muscle fibers, and clinical attributes of muscle weakness and respiratory insufficiency. Respiratory problems in CNMs may manifest initially during sleep, but daytime symptoms, ineffective airway clearance, and hypoventilation predominate as more severe respiratory muscle dysfunction evolves. Respiratory muscle capacity can be evaluated using a variety of clinical tests selected with consideration for the age and baseline motor function of the patient. Similar clinical tests of respiratory function can also be incorporated into preclinical CNM canine models to offer insight for clinical trials. Because respiratory problems account for significant morbidity in patients, routine assessments of respiratory muscle function are discussed.

Keywords: canine; genetics; muscle disease; myopathy; respiratory assessment.

Figure 1

Maximum inspiratory pressure in a tracheostomized, mechanically ventilated child with XLMTM. The patient was briefly removed from the ventilator, and a one-way valve was placed over the tracheostomy opening. Negative pressure deflections indicate inspiratory efforts, while exhalation was unobstructed. The most negative pressure in 20 seconds (circled) was the maximum inspiratory pressure.

Figure 2

Breathing pattern compensation in dogs with XLMTM. A. Peak inspiratory (PIF) and expiratory (PEF) flow increase in response to a respiratory stimulant, doxapram chloride. B. Inspiratory time (TI) and expiratory time (TE) in response to doxapram. XLMTM dogs maintain their respiratory rate (C), while they increase tidal volume (D) in response to respiratory stimulation with doxapram.

Figure 3

Thoracoabdominal motion in an anesthetized A. normal and B XLMTM dog 45s after stimulation with doxapram chloride (1.0mg/kg). While thoracic and abdominal motion are synchronous in the normal dog (boxed area in A), paradoxical thoracic motion (boxed area in B) was detected during stimulation in the XLMTM dog. Note also the difference in the thoracic (green) waveform in panel B vs. panel A.

Figure 4

Qualitative thoracoabdominal motion in a mechanically-ventilated boy with XLMTM, showing relative displacements of the thoracic and abdominal bands coinciding with breathing. A. On resting support, thoracic and abdominal displacement was coordinated, with a slow, regular respiratory pattern. B. At the lowest level of support, paradoxical thoracic motion (arrows) was detected during inspiratory efforts (* = sigh breath delivered by the ventilator).