Diverse abnormalities of corticomotoneuronal projections in individual patients with amyotrophic lateral sclerosis

Abstract

Using peristimulus time histograms (PSTHs), abnormalities of composite excitatory postsynaptic potentials (EPSPs) induced by transcranial magnetic stimulation were studied in multiple motor units from individuals with amyotrophic lateral sclerosis (ALS) and normal subjects. We studied 97 motor units in the extensor digitorum communis muscle of 22 patients with sporadic ALS and 47 motor units of 10 healthy control subjects. Four or five motor units were studied in each patient and normal subject. For each unit, macro motor unit potentials (Macro-MUPs) were simultaneously recorded from a surface electrode after spike-triggered averaging. The composite EPSPs in ALS showed a generally bi-directional deviation from the normal curve, with small EPSPs at one end, and larger amplitude EPSPs with a prolonged rise time at the other end. The variability of EPSPs from adjacent motor units in the same individual was significantly larger in ALS than in controls. In normal subjects there is a significant negative correlation between the amplitude of composite EPSPs and the Macro-MUPs. In ALS, the trend is reversed (positive) suggesting that the abnormalities of composite EPSPs are supraspinal in origin. A combination of partial attrition of the corticomotoneuronal core and hyper-excitability of surviving corticomotoneurons projecting to a given spinal motoneuron pool best explains the diversity of the composite EPSP in individuals with ALS.