Fibre type‐specific increase in passive muscle tension in spinal cord‐injured subjects with spasticity

Abstract

Patients with spasticity typically present with an increased muscle tone that is at least partly caused by an exaggerated stretch reflex. However, intrinsic changes in the skeletal muscles, such as altered mechanical properties of the extracellular matrix or the cytoskeleton, have been reported in response to spasticity and could contribute to hypertonia, although the underlying mechanisms are poorly understood. Here we examined the vastus lateralis muscles from spinal cord-injured patients with spasticity (n = 7) for their passive mechanical properties at three different levels of structural organization, in comparison to healthy controls (n = 7). We also assessed spasticity-related alterations in muscle protein expression and muscle ultrastructure. At the whole-muscle level in vivo, we observed increased passive tension (PT) in some spasticity patients particularly at long muscle lengths, unrelated to stretch reflex activation. At the single-fibre level, elevated PT was found in cells expressing fast myosin heavy chain (MyHC) isoforms, especially MyHC-IIx, but not in those expressing slow MyHC. Type IIx fibres were present in higher than normal proportions in spastic muscles, whereas type I fibres were proportionately reduced. At the level of the isolated myofibril, however, there were no differences in PT between patients and controls. The molecular size of the giant protein titin, a main contributor to PT, was unchanged in spasticity, as was the titin : MyHC ratio and the relative desmin content. Electron microscopy revealed extensive ultrastructural changes in spastic muscles, especially expanded connective tissue, but also decreased mitochondrial volume fraction and appearance of intracellular amorphous material. Results strongly suggest that the global passive muscle stiffening in spasticity patients is caused to some degree by elevated PT of the skeletal muscles themselves. We conclude that this increased PT component arises not only from extracellular matrix remodelling, but also from structural and functional adaptations inside the muscle cells, which alter their passive mechanical properties in response to spasticity in a fibre type-dependent manner.

The length–tension relationship of human dorsiflexor and plantarflexor muscles after spinal cord injury

“…Olsson et al 10 showed a MHC type IIx-dependent increase in muscle stiffness, as measured by passive tension, after SCI. This increase was particularly apparent at long muscle lengths.…”

“…8,9 This increase in connective tissue contributes to a loss of elasticity, an increase in passive tension and a decrease in range of motion. [7][8][9][10] To date, only two studies have attempted to address changes in the length-tension relationship after SCI. Gerrits et al 11 found no change in the torque-angle relationship of human knee extensors compared with controls, although the SCI participants produced significantly less torque (relative to their own maximum) at extreme angles.…”

Muscle-specific changes in length-force characteristics of the calf muscles in the spastic Han-Wistar rat

“…One study using biopsies from human spastic muscles has reported an increased passive tension in type II muscle fibers, but not in type I muscle fibers (36), which may contribute to muscle-specific effects of spasticity. In addition, SO is constantly active during low-intensity tasks such as standing and walking, whereas GA and PL are activated appreciably during tasks involving greater mechanical demands, such as running and jumping (22).…”

Muscle rupture after minimal trauma of the spastic muscle: three case reports of patients with spinal cord injury

“…The fibers of a spastic muscle are stiffer than normal muscles, and fail on a shorter sarcomere length during elongation. In the spastic muscle, there is a relative increase in type II fibers, 3 it being more easily affected. Previous research on muscle pain after eccentric exercise has shown that type II fibers are also more sensitive to mechanical stress.…”

“…The collagen fibers, however, are much less structured and are much more fragile. 3 In persons with a spinal cord injury, anesthesia below the level of lesion is an intrinsic risk factor. Reduced or absent pain sensation, in combination with paresis renders apprehensive reactions impossible.…”