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A computer model of the process of denervation and complete reinnervation of skeletal muscle has been developed for the purpose of exploring underlying mechanisms and for use in the development of new clinical and research tools for evaluating neuromuscular disease. Progressive motor neuron death and reinnervation in this model reproduces the fiber-type grouping, increased fiber density, and minimal increase of motor unit size seen in human chronic denervating diseases. Studies using the model suggest that (1) preferential involvement of motor units of one type could account for the abnormal fiber-type proportions observed in some diseases, (2) reinnervation by axons innervating adjacent fibers is compatible with single fiber multielectrode study results in that it does not produce a large increase in motor unit area, and (3) such reinnervation is sufficient to account for the increases in motor unit density that have been observed. The model has also been used in the development and testing of the Codispersion Index, a measure of the codistribution of two fiber types, which is useful in detecting fiber-type grouping.

There is a need for a practical and statistically manageable quantitative index of fiber type co-dispersion in skeletal muscle to allow investigation of the distribution of motor units in normal muscle and their rearrangement in pathological states. A new measure for this purpose, the Co-Dispersion Index (CDI), is introduced. This measure is based on contingency table analysis of nearest-neighbor relationships between muscle fibers. The CDI has a continuous range of values from -1 to +1, in which larger negative values indicate a greater tendency toward regular intermixing of fibers of different types, and larger positive values a greater segregation of fiber types. CDI evaluation overcomes the limitations of previously published quantitative methods for co-dispersion measurement and is well correlated with subjective human estimates of fiber type grouping.