Neurophysiological evaluation of cortical function in the early diagnosis of ALS

The corticomotoneuronal system is selectively vulnerable in amyotrophic lateral sclerosis (ALS). In the past it has been difficult to evaluate the upper motor neuron component of this system. Recent studies using functional imaging and neurophysiological methods are now available as potential surrogate markers in the early diagnosis of ALS. We have used peristimulus time histograms (PSTHs) to evaluate the integrity of the motor cortex in ALS and in particular the cortical colonies that synapse with single anterior horn cells. The motor cortex in ALS becomes hyperexcitable early in the course of the disease and this may persist for some time. This is reflected in the PSTH by a desynchronized, complex response. Evidence indicates that this prime abnormality in ALS is supraspinal in origin and probably due to increased repetitive firing of the corticomotoneuron. The hyperexcitability is likely to be due to a combination of increased excitation at the level of the motor cortex and decreased inhibition due to dysfunction of the cortical inhibitory interneurones that modulate the output of the corticomotoneurone.