Involvement of spinal recurrent inhibition in spasticity. Further insight into the regulation of Renshaw cell activity.

Abstract

Changes in the excitability of the soleus H-reflex are were studied after oral administration of L-acetylcarnitine, a cholinomimetic substance, in eight healthy control subjects and 23 spastic patients presenting with slowly progressive paraparesis (n = 10), a cord lesion (n = 9) and a cerebral lesion (n = 4). Changes in the amount of recurrent inhibition of soleus motor neurons at rest were also estimated in order to assess the level of activity of Renshaw cells before and after L-acetylcarnitine administration. Recurrent inhibition elicited by a conditioning reflex discharge (H1) was assessed by a subsequent test reflex (H'). Four patients lacked an H' reflex. In approximately 50% of the remaining patients, recurrent inhibition was normal, while in the other half there was evidence of reduced or absent inhibitory activity at rest. Pooling the data relative to the effect of L-acetylcarnitine on the H-reflex in relation to the strength of recurrent inhibition disclosed that the ratio of peak-to-peak amplitude values of the maximum H reflex to maximum M wave responses (Hmax:Mmax) was reduced in all the cases in which the recurrent inhibition at rest was normal, while such a reduction was never observed in the patients in whom recurrent inhibition was found to be decreased at rest. In the former cases, the size of the H' reflex evoked by the same conditioning H1 discharge was further depressed after L-acetylcarnitine, pointing to a potentiating effect of the drug on Renshaw cells; in the latter cases no such effect was seen. A significant decrease in the mean Hmax:Mmax ratio after L-acetylcarnitine intake was also seen in the healthy control subjects. Possible changes in the amount of presynaptic inhibition on Ia terminals on soleus motor neurons after L-acetylcarnitine were ruled out. It is proposed that the differential effect of the drug on the H-reflex excitability is directly related to the level of Renshaw cell activity, a reduction of which probably follows a lesion interrupting reticulo-spinal pathways with tonic facilitatory influences on Renshaw cells. These findings support the hypothesis that Renshaw cell excitability is set via cortico-reticulo-spinal systems.