Dileone Michele, Ranieri Federico, Florio Lucia, Capone Fioravante, Musumeci Gabriella, Leoni Chiara, Mordillo-Mateos Laura, Tartaglia Marco, Zampino Giuseppe, Di Lazzaro Vincenzo
Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain; Department of Neurosciences, San Bortolo Hospital, Vicenza, Italy; CINAC, HM Puerta del Sur, Hospitales de Madrid, 28938 Móstoles, Spain.
Institute of Neurology, Campus Biomedico University, Rome, Italy; Fondazione Alberto Sordi - Research Institute for Ageing, Rome, Italy.
Brain Stimul. 2016 Jan-Feb;9(1):33-8. doi: 10.1016/j.brs.2015.08.012. Epub 2015 Sep 2.
Costello syndrome (CS) is a rare congenital disorder due to a G12S amino acid substitution in HRAS protoncogene. Previous studies have shown that Paired Associative Stimulation (PAS), a repetitive brain stimulation protocol inducing motor cortex plasticity by coupling peripheral nerve stimulation with brain stimulation, leads to an extremely pronounced motor cortex excitability increase in CS patients. Intermittent Theta Burst Stimulation (iTBS) represents a protocol able to induce motor cortex plasticity by trains of stimuli at 50 Hz. In healthy subjects PAS and iTBS produce similar after-effects in motor cortex excitability. Experimental models showed that HRAS-dependent signalling pathways differently affect LTP induced by different patterns of repetitive synaptic stimulation.
We aimed to compare iTBS-induced after-effects on motor cortex excitability with those produced by PAS in CS patients and to observe whether HRAS mutation differentially affects two different forms of neuromodulation protocols.
We evaluated in vivo after-effects induced by PAS and iTBS applied over the right motor cortex in 4 CS patients and in 21 healthy age-matched controls.
Our findings confirmed HRAS-dependent extremely pronounced PAS-induced after-effects and showed for the first time that iTBS induces no change in MEP amplitude in CS patients whereas both protocols lead to an increase of about 50% in controls.
CS patients are characterized by an impairment of iTBS-related LTP-like phenomena besides enhanced PAS-induced after-effects, suggesting that HRAS-dependent signalling pathways have a differential influence on PAS- and iTBS-induced plasticity in humans.
科斯特洛综合征（CS）是一种罕见的先天性疾病，由HRAS原癌基因中的G12S氨基酸替换引起。先前的研究表明，配对联想刺激（PAS）是一种通过将外周神经刺激与脑刺激相结合来诱导运动皮层可塑性的重复性脑刺激方案，可导致CS患者的运动皮层兴奋性极度显著增加。间歇性θ波爆发刺激（iTBS）是一种能够通过50Hz的刺激序列诱导运动皮层可塑性的方案。在健康受试者中，PAS和iTBS在运动皮层兴奋性方面产生相似的后效应。实验模型表明，HRAS依赖的信号通路对不同模式的重复性突触刺激诱导的长时程增强（LTP）有不同影响。
我们旨在比较iTBS和PAS对CS患者运动皮层兴奋性的后效应，并观察HRAS突变是否对两种不同形式的神经调节方案有不同影响。
我们评估了4例CS患者和21例年龄匹配的健康对照者右侧运动皮层接受PAS和iTBS刺激后的体内后效应。
我们的研究结果证实了HRAS依赖的PAS诱导的极度显著后效应，并首次表明iTBS在CS患者中未引起运动诱发电位（MEP）幅度的变化，而在对照组中两种方案均导致MEP幅度增加约50%。
CS患者除了PAS诱导的后效应增强外，还存在iTBS相关的LTP样现象受损，这表明HRAS依赖的信号通路对人类PAS和iTBS诱导的可塑性有不同影响。
