Lamy Jean-Charles, Wargon Isabelle, Mazevet Dominique, Ghanim Zaïd, Pradat-Diehl Pascale, Katz Rose
Inserm, U731, F-75013, Paris, France.
Brain. 2009 Mar;132(Pt 3):734-48. doi: 10.1093/brain/awn310. Epub 2008 Nov 26.
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.
痉挛的病理生理机制一直是众多研究的主题。在各类痉挛患者中进行的这些研究揭示了许多控制运动神经元放电的脊髓通路存在异常。遗憾的是，导致痉挛发展的病理生理机制在很大程度上仍然未知，因为之前的大多数研究未能揭示痉挛特征（严重程度、时间进程）与特定受扰脊髓通路功能障碍特征之间的联系。在本系列实验中，我们聚焦于研究作用于Ia纤维-运动神经元突触的突触前机制，因为在痉挛状态下单突触反射会增强。在动物和人类中都描述了两种突触前机制：突触前Ia抑制和激活后抑制。通过与之前的研究相比增加受试者数量（87例患者和42名健康对照），我们得以表明，在中风患者中，这两种机制受损程度不同，具体取决于（i）疾病持续时间（急性，定义为致病损伤后少于3个月，或慢性，定义为致病损伤后多于9个月），（ii）所考虑的侧别（患侧或未患侧）以及（iii）痉挛的严重程度。在这方面，仅发现激活后抑制量与痉挛严重程度高度相关。尽管并非确凿证据，但痉挛严重程度与特定脊髓通路变化之间的这种相关性使我们得出结论，激活后抑制受损可能是痉挛的潜在机制之一。相反，突触前Ia抑制的变化似乎只是一种附带现象，即脑损伤的一种基本关联。有人认为，这两种通路中由于运动指令受损导致的废用会引发可塑性变化。
