Nerve Conduction Studies as a Measure of Disease Progression: Objectivity or Illusion?

Clinical nerve conduction studies (NCS) are often used as a secondary outcome measure in therapeutic trials, but show a high degree of inter-trial variability even when technical factors known to affect the recorded responses are minimised. This raises the intriguing possibility that some of the observed variability may reflect true changes in nerve activity.

Our aim was determine how much variability these factors might produce, and how this might affect the results of commonly used neuropathy rating scales.

A standardised protocol was repeated over forty consecutive trials by the same operators in two healthy subjects. The protocol included recordings that shared either a stimulating or a recording electrode position, such that changes due to electrode position could be excluded, and hand temperature was closely controlled.

Despite controlling for inter-operator differences, electrode position, and hand temperature, the variability in sensory nerve action potential (SNAP) amplitude was extremely high (Range 23 μV, CoV = 10.7-18.8). This variability was greater than the change in amplitude needed to move a subject from point 0 to point 4 on the CMT neuropathy rating scale. Neither temperature or electrode position accounted for all of this variability, suggesting that additional as yet unidentified factors are responsible.

Even under closely controlled conditions and sophisticated laboratory methods, test-to-test variability can be significant. The factors responsible for this variability may be difficult to control, limiting the utility of single nerve recordings as a trial outcome measure.