痉挛性斜颈肉毒毒素治疗前后脑功能磁共振成像研究

The functional magnetic resonance imaging study of cervical dystonia and its modulation with botulinum toxin

目的应用脑功能磁共振成像（functiona lmagnetic resonance imaging，fMRI）技术，观察痉挛性斜颈（torticollis，idiopathiccervicaldystonia，CD）患者行对指动作时的脑激活模式及肉毒毒素局部肌内注射前后的变化，探讨CD可能的发病机制和肉毒毒素治疗后的中枢水平改变。方法采用fMRI组块设计，分别获得CD患者11例于接受肉毒毒素局部注射前、后4周以及性别年龄匹配的健康志愿者11名执行复杂对指动作任务时的有效脑功能激活图。比较患者治疗前、后与健康对照组的激活差异；以多伦多西方CD等级量表（TWSTRS）评价并比较患者治疗前后症状严重度。分析肉毒毒素治疗所致脑激活水平变化与临床症状评分改变的相关性。结果CD患者行头扭转同侧对指动作时，同侧壳核、同侧前额叶皮质、对侧初级体皮质等处激活较健康对照明显减低，而同侧楔前叶、同侧梭状回处激活增高。经肉毒毒素治疗后4周CD患者脑内激活水平较健康对照仅对侧楔前叶处减低，其余脑区差异无统计学意义。经肉毒毒素治疗CD患者TWSTRS评分减低，由治疗前（20．02±5．52）分降至治疗后（4．11±4．34）分，其差异有统计学意义（t=11．71，P=0．000）。肉毒毒素治疗前后脑激活水平变化在下列脑区与TWSTRS评分改变呈正相关：头扭转方向同侧初级体感皮质、前运动皮质、辅助运动皮质、岛叶、梭状回、海马及海马旁回，对侧颞中回、海马及海马旁回等。结论CD患者存在皮质及皮质下的广泛脑内激活模式异常，可能与感觉运动整合功能紊乱有关，且受累肢体于临床症状出现前可能已处于“预痉挛”状态。肉毒毒素局部注射后CD患者脑内激活模式趋于正常，其机制可能为大脑皮质的功能重塑。

Objective To observe the cerebral activation pattern in patients with cervical dystonia （CD） during finger movements and the changes caused by botulinum toxin injection by functional MRI. The possible etiological mechanism of CD and effect of peripheral botulinum toxin treatment on the level of central nerves system are investigated. Methods A designed functional MRI block with complex finger movements was applied and 11 patients with CD as well as 11 age and gender matched controls were scanned. Compare the activation pattern of CD pre/post treatment groups versus health controls. Evaluate and compare the symtom severity with Toronto Western Spasmodic Tortieollis Rating Scale （TWSTRS）. Make a correlation analysis between activation pattern alteration and TWSTRS change in CD pre/post treatment groups. Results An reduced extent of activation in patients with CD was demonstrated compared to healthy controls in ipsilateral putamen, prefrontal cortex and contralateral somatosensory cortex to the direction of the head deviation, while an elevated extent of activation in ipsilateral preeuneus and fusiform with statistic significance. At the time point of 4 weeks after botulinum toxin treatment patients showed no evident difference with healthy controls except for the decreased activation in contralateral precuneus to the direction of the head deviation. TWSTRS of patients with CD decreased from （20.02 ±5.52） to （4.11± 4.34） with statistic significance （t = 11. 71, P = 0. 000 ） after botulinum toxin treatment. There was a positive correlation between cerebral activation pattern change in some cerebral areas （ipsilateral primarysomatosensory cortex, premotor cortex, supplementary motor cortex, insula, fusiform, hippocampus with parahippocampa as well as contralateral middle temporal cortex and hippocampus with parahippocampa to the direction of the head deviation ） and TWSTRS score decrease. Conclusions There are widespread abnormalities in cortical and subcortical activation pattern in patients with CD, which might due to dysfunction of sensory-motor integration. We speculate a basic pre-dystonic state is present in affected body parts prior to clinical symptoms appear. Botulinum toxin fulfills its subsequent central effect by reorganizing and normalizing the cerebral cortex in patients with CD.