Contributor: Dan Knauss

Researchers in Japan have published results from a study measuring how much motor nerve function has declined over time in people with CMT1A, comparing their nerve activity to that of unaffected individuals.

How the Study Worked

Nineteen people with CMT1A were tested using high-density surface electromyography (surface-EMG), a non-invasive technique that records electrical activity in muscles. The equipment was applied to participants’ thighs during isometric knee extensions (a seated exercise in which the lower leg is raised to a position parallel to the floor). The study focused on the largest portion of the quadriceps, the muscle group responsible for extending the knee.

Researchers recorded the firing rate of individual motor units (the basic contractile units of muscle: a motor neuron, its axon, and the muscle fibers it activates) at two points separated by one year. The same tests were carried out on a control group of people without CMT1A.

What the Results Showed

People with CMT1A showed lower instantaneous firing rates (IFRs) than the control group, and those rates declined further over the one-year period without any outwardly visible changes in muscle function. This consistent, measurable drop suggests that surface-EMG could serve as a practical tool for tracking CMT1A progression.

The study also allowed researchers to compare average firing rates between the two groups, providing a way to quantify how much CMT1A has affected motor nerve and muscle function relative to a healthy baseline.

Understanding Motor Units and CMT1A

Although CMT1A is primarily a demyelinating neuropathy (one that damages the myelin sheath protecting nerves), axonal damage also occurs alongside demyelination. A single motor unit’s firing rate is proportional to the force that unit needs to produce. Groups of motor units called a “motor pool” fire together to produce the strongest possible contraction. When CMT1A impairs firing rates, muscle contractions are weaker even when a large motor pool is activated.

Specific Findings on Force and Fatigue

The study found that CMT1A affects all levels of force generation. There was no decrease in maximum voluntary contraction (MVC), a standard measure of peak muscle strength in neuromuscular disease. However, average firing rates differed between groups:

  • During ramp-up contractions, the CMT1A group averaged 10.3 pulses per second (pps) versus 12.2 pps in the control group.
  • During sustained contractions, the CMT1A group averaged 8.0 pps versus 9.3 pps in the control group.
  • Within the CMT1A group, average firing rates during sustained contractions fell from 8.06 to 7.52 pps, indicating fatigue.

The researchers also noted a connection to an earlier surface-EMG study showing lower motor cortex activity in CMT1A patients when planning leg movements. That earlier study found higher-than-normal activity in the prefrontal cortex, which may be compensating for reduced motor cortex activation. The conscious effort required to move muscles could itself be both a cause and a result of the fatigue that people with CMT commonly experience.

Together, these studies provide objective measures and tools for assessing the severity and progression of CMT1A, which could prove valuable for future clinical trials.