The equations of life and death

Abstract

As the therapeutic revolution in neurology advances, the number of pharmacologic and regenerative therapies grows ever larger. With this abundance, however, comes the challenge of properly identifying which therapies warrant the substantial investments required for full-scale human trials; sensitive assessment of treatment effects is therefore paramount. Disease progression, as the sum of injury due to the disease minus the countervailing effects of the patient's own compensatory systems, is a relevant but hard to measure outcome. While many biomarkers track primary disease activity, most proposed regenerative therapies (e.g., stem cells, growth factors, genetic re-engineering) act primarily through compensation and repair. Unfortunately, comparatively few assays provide a sound measure of compensation or repair, and even fewer assays provide simultaneous information about both disease activity and compensation. A motor unit number estimate (MUNE) can be calculated by taking a value representing all the motor units subserved by a nerve and dividing by a similar value representing the typical single motor unit in that nerve (usually, such values are size parameters). Just as the familiar maximal compound motor action potential (CMAP), obtained during the routine motor nerve conduction study, provides an electrophysiologic measure of all the …