Novel method for physiological recruitment of diaphragm motor units after upper cervical spinal cord injury.

EACH YEAR, approximately 11,000 people in the United States suffer cervical spinal cord injury that results in partial or complete diaphragm muscle paralysis with an annual expense of more than $3 billion. Those unable to maintain adequate ventilation due to diaphragm muscle paralysis become dependent on mechanical ventilators, a situation associated with ongoing problems related to pulmonary clearance, infections, and lung injury that lead to significant morbidity and increased mortality. Therefore, restoration of diaphragm muscle activity and the ability to accomplish ventilatory and nonventilatory motor behaviors (e.g., cough) would dramatically impact the quality of life of mechanical ventilator-dependent patients with cervical spinal cord injury. For some time, functional electrical stimulation of the phrenic nerve has been used to restore diaphragm muscle activity and thereby ameliorate patient dependency on mechanical ventilation. However, due to the intrinsic electrophysiological constraints associated with electrical stimulation of peripheral nerves, over 50% of potentially eligible patients fail to obtain adequate diaphragm activation to sustain full-time ventilatory support. Moreover, electrical activation of only the diaphragm muscle misses the normal physiological advantage of stabilizing the chest wall through mechanical coupling of diaphragm and intercostal muscle activity. The study by DiMarco and Kowalski (4) in the Journal of Applied Physiology presents a novel stimulation technique that restores more normal physiological activation of the diaphragm muscle as well as coordinated activation of the diaphragm and intercostal muscles. This important proof of principle study represents the beginning stage of a therapeutic approach that may reduce morbidity and mortality associated with mechanical ventilation, thus restoring quality of life to thousands of spinal cord injury patients. To better understand the significance of this study, it is important to understand normal recruitment of motor units, the fundamental building blocks of neuromotor control. Liddell and Sherrington (7) originally proposed that neural control of muscle force generation results from a combination of an orderly recruitment of motor units together with changes in motoneuron discharge frequency. Later, Henneman et al. (6) proposed that orderly recruitment of motor units was due to the intrinsic, size-related electrophysiological properties of motoneurons such that with similar synaptic input currents, smaller motoneurons with smaller axons, and thus slower axonal conduction velocities, are recruited before larger motoneurons (“size principle”). Dick and colleagues found that during spontaneous breathing in cats, those phrenic motoneurons recruited first had slower axonal conduction velocities compared with motoneurons recruited later (3), thus confirming the size principle in the diaphragm. A relationship between recruitment order and the mechanical properties of motor units has also been demonstrated (Fig. 1), which forms the basis for classifying different motor unit types (1, 5, 9, 11). Smaller motoneurons innervate slow-twitch muscle fibers (i.e., type I fibers comprising type S motor units) that generate lower maximum tetanic force, have a leftward-shifted force-frequency response curve, and display greater fatigue resistance during repetitive stimulation. Larger motoneurons innervate fast-twitch muscle fibers (type II muscle fibers) that generate greater maximum tetanic force, have a rightward-shifted force-