Cortical excitability in amyotrophic lateral sclerosis: a clue to pathogenesis

Motor evoked potentials (MEPs) were recorded from selected non-wasted, non-denervated hand muscles in 40 patients with Amyotrophic Lateral Sclerosis (ALS) with both upper and lower motor neuron signs. In most the compound muscle action potential (CMAP) of the target muscle was normal. Compared to the control group, cortical threshold in ALS varied considerably and there was a significant (r2 = 0.702) inverse, exponential, correlation between cortical threshold and MEP/CMAP ratio. There was a linear correlation between threshold and disease duration (r2 = 0.66) so that early in the disease threshold was normal and later the motor cortex could not be stimulated. It is suggested that early in ALS normal threshold reflects glutamate-induced hyper-excitability of the corticomotoneuron. The findings lend support to the hypothesis that ALS is primarily a disease of the corticomotoneuron.