Impaired efficacy of spinal presynaptic mechanisms in spastic stroke patients

Abstract

Pathophysiological mechanisms underlying spasticity have been the subject of many studies. These studies performed in various kinds of spastic patients have revealed abnormalities in many spinal pathways controlling motoneurone discharge. Unfortunately, the pathophysiological mechanisms responsible for the development of spasticity remains nevertheless largely unknown since most of the previous studies failed to reveal a link between the characteristics of spasticity (severity, time course) and that of the dysfunction of a given perturbed spinal pathway. In the present series of experiments, we focused on the study of presynaptic mechanisms acting at the synapse fibre Ia-motoneurone since monosynaptic reflexes are enhanced in spasticity. Two presynaptic mechanisms have been described in both animals and humans: presynaptic Ia inhibition and post-activation depression. By increasing the number of subjects in comparison with previous studies (87 patients and 42 healthy controls) we have been able to show that these two mechanisms are unequally impaired in stroke patients depending on (i) the duration of the disease (acute, defined as less than 3 months after the causal lesion, or chronic, defined as more than 9 months after the causal lesion), (ii) the side considered (affected or unaffected) and (iii) the severity of spasticity. In this respect, only post-activation depression amount was found to be highly correlated with the severity of spasticity. Although not a definitive proof, this correlation between severity of spasticity and changes in a given spinal pathway lead us to conclude that the impairment of post-activation depression is likely one of the mechanisms underlying spasticity. On the contrary, changes in presynaptic Ia inhibition appear to be a simple epiphenomenon, i.e. a basic correlate of the brain lesions. It is argued that plastic changes develop from the disuse due to motor command impairment in both pathways.

Post-activation depression of the lower extremities in stroke patients with spasticity and spastic equinovarus deformity

“…Previous studies have revealed a significant positive correlation between reduced post-activation depression and spasticity severity 6,7 . Our results provide additional evidence for this relationship.…”

“…H-reflex depression is striking at short breaks (1-2 s between two successive stimulations). In contrast, the depression is not obvious when the stimulation intervals are 8 s or longer 7 . Decreased synaptic neurotransmitter release may be responsible for the depression, which is most obvious in resting individuals and is weak or absent when the tested muscle is voluntarily activated 8,10 .…”

“…abnormality correlates with the degree of spasticity 7 and is not observed on the nonparetic side. Although it was reported that other pathways can be changed to different extents in patients with CNS lesions, contradictory results are published in the literature.…”

“…This is called the 1/10s ratio, and a greater value indicates less postactivation depression. Special attention was paid to ensure that the tested muscle was at complete rest because post-activation depression is reduced when the muscle is voluntarily contracted 7 . Post-activation depression was determined bilaterally.…”

Immediate effects of TENS and cryotherapy in the reflex excitability and voluntary activity in hemiparetic subjects: a randomized crossover trial

“…These alterations may be caused by a loss of supraspinal control. In these conditions, treatment that aims to modulate the excessive impulses or the system of inter neurons becomes useful 34 . Activating large diameter afferent nerve fibers through TENS may modulate interneuron activities in several spinal segments, which then activate inhibition mechanisms of the presynaptic nerve 17 .…”