Muscle stiffness and possible therapeutic interventions in children with cerebral palsy

Cerebral palsy (CP) is the most common cause of spasticity and physical disability in children. Muscle overactivity from chronic spasticity appears to result in increased passive muscle stiffness. This stiffness results in loss of passive range of motion (PROM) and may be a major factor in physical function as children with CP grow into adulthood.

"Excessive muscle stiffness in children has great implications for functional development into adulthood," explains Joline E. Brandenburg, M.D., of the Department of Physical Medicine and Rehabilitation at Mayo Clinic in Rochester, Minn. "Too much stiffness can lead to deformity and decreased function."

Passive muscle stiffness is the resistance of muscle-tendinous unit to change length — the stiffness felt when executing range-of-motion activities. Too much stiffness may affect muscle contraction coordination and muscle activation, and it can also lead to limits in range of motion and contractures or bony deformity. "We know that muscle force is influenced by length of muscle," explains Dr. Brandenburg. "So if the muscle is shortened by stiffness, this stiffness limits the force that can be generated."

When comparing children who have CP with typically developing age-matched children, one study noted that it took three times more force to stretch the calf muscle in children with CP than in typically developing children. Using muscle biopsy, other researchers have observed that spastic muscles are stiffer and that the content of these muscles is different. The muscles of children with CP have an increase in collagen in the extracellular matrix, an increase in sarcomere length and fewer sarcomeres in series. All of these differences may affect the ease with which muscles can be stretched.

Therapeutic interventions for PROM are geared toward managing spasticity, with many focusing on the muscle or the neuromuscular junction. These include stretching, serial casting and botulinum neurotoxin (BoNT). "While some improvement of muscle PROM after BoNT treatment has been observed, several recent studies have shown that BoNT does not act directly on the muscle and affect muscle stiffness, and others have offered mixed reviews of BoNT's effects on muscle function," explains Dr. Brandenburg.

One of the problems that researchers encounter when attempting to evaluate the effectiveness of therapeutic interventions for muscle stiffness is the lack of precise measuring tools appropriate for use with children in the clinical setting. Clinical measurements of PROM and spasticity scales can provide some information, but they can yield imprecise and subjective information. Obtaining an accurate measurement of passive muscle stiffness noninvasively in the clinical setting would help providers monitor the effect and duration of effect of interventions such as BoNT, thereby guiding treatment.

Dr. Brandenburg and Mayo colleagues are currently studying the use of an ultrasound elastography technique called shear wave ultrasound elastography to quantify passive muscle stiffness in children with CP before and after BoNT injections. This technique uses a commercially available, Food and Drug Administration-approved ultrasound machine that is equipped with a probe that generates shear waves in tissue. Shear waves are generated by ultrasound push beams. These shear waves are tracked by pulse-echo ultrasound and measured using computer algorithms. This calculation provides a quantitative measure of stiffness that is based on how quickly the shear waves move through the tissue, the density of the tissue and the area of tissue measured.

The Mayo team is using this technique in an ongoing study of muscle stiffness patterns in the gastrocnemius muscles of typically developing children and children with CP undergoing treatment with BoNT. Using EMG to monitor muscle activity, researchers gently stretch the children's calf muscles, measuring the stiffness of the gastrocnemius muscle at varying positions. Although they are still recruiting subjects and collecting data, the preliminary findings from this research are pointing to the following conclusions:

  • Laxity and muscle stiffness is different in children with CP.
  • BoNT appears to have a minimal effect on muscle stiffness and in some cases may have a rebound effect.
  • Loss of treatment efficacy may be detected by the absence of significant change in muscle stiffness.
  • Muscle activation among research subjects must be controlled because it can influence measurements of passive muscle stiffness.

Dr. Brandenburg is hopeful that by providing target levels of normal passive muscle stiffness, this research may help identify effective spasticity management strategies and guide timing of use of these strategies for children with CP.

Points to remember

  • Passive muscle stiffness results in loss of passive range of motion in children with cerebral palsy. As children grow, this stiffness can lead to deformity and decreased function.
  • Therapeutic interventions for passive range of motion are geared toward managing spasticity, with many focusing on the muscle or the neuromuscular junction. These include stretching, serial casting and botulinum neurotoxin.
  • Mayo Clinic researchers are currently investigating the use of an ultrasound elastography technique called shear wave ultrasound elastography to quantify passive muscle stiffness in children with cerebral palsy before and after BoNT injections.