Blood Anne J, Kuster John K, Waugh Jeff L, Levenstein Jacob M, Multhaupt-Buell Trisha J, Sudarsky Lewis R, Breiter Hans C, Sharma Nutan
Mood and Motor Control Laboratory, Massachusetts General Hospital (MGH), Charlestown, MA, United States.
Laboratory of Neuroimaging and Genetics, Massachusetts General Hospital, Charlestown, MA, United States.
Front Neurol. 2019 Apr 4;10:265. doi: 10.3389/fneur.2019.00265. eCollection 2019.
In a previous report showing white matter microstructural hemispheric asymmetries medial to the pallidum in focal dystonias, we showed preliminary evidence that this abnormality was reduced 4 weeks after botulinum toxin (BTX) injections. In the current study we report the completed treatment study in a full-size cohort of CD patients ( = 14). In addition to showing a shift toward normalization of the hemispheric asymmetry, we evaluated clinical relevance of these findings by relating white matter changes to degree of symptom improvement. We also evaluated whether the magnitude of the white matter asymmetry before treatment was related to severity, laterality, duration of dystonia, and/or number of previous BTX injections. Our results confirm the findings of our preliminary report: we observed significant fractional anisotropy (FA) changes medial to the pallidum 4 weeks after BTX in CD participants that were not observed in controls scanned at the same interval. There was a significant relationship between magnitude of hemispheric asymmetry and dystonia symptom improvement, as measured by percent reduction in dystonia scale scores. There was also a trend toward a relationship between magnitude of pre-injection white matter asymmetry and symptom severity, but not symptom laterality, disorder duration, or number of previous BTX injections. analyses suggested the FA changes at least partially reflected changes in pathophysiology, but a dissociation between patient perception of benefit from injections and FA changes suggested the changes did not reflect changes to the primary "driver" of the dystonia. In contrast, there were no changes or group differences in DTI diffusivity measures, suggesting the hemispheric asymmetry in CD does not reflect irreversible white matter tissue loss. These findings support the hypothesis that central nervous system white matter changes are involved in the mechanism by which BTX exerts clinical benefit.
在之前一份显示局灶性肌张力障碍患者苍白球内侧白质微观结构半球不对称性的报告中，我们展示了初步证据，即肉毒毒素（BTX）注射4周后这种异常有所减轻。在当前研究中，我们报告了对一组完整规模的痉挛性斜颈（CD）患者（n = 14）的完整治疗研究。除了显示半球不对称性向正常化转变外，我们通过将白质变化与症状改善程度相关联，评估了这些发现的临床相关性。我们还评估了治疗前白质不对称性的程度是否与肌张力障碍的严重程度、偏侧性、持续时间和/或既往BTX注射次数有关。我们的结果证实了初步报告的发现：我们观察到CD参与者在BTX注射4周后苍白球内侧的分数各向异性（FA）有显著变化，而在相同时间间隔扫描的对照组中未观察到这种变化。半球不对称性的程度与肌张力障碍症状改善之间存在显著关系，肌张力障碍症状改善程度通过肌张力障碍量表评分的降低百分比来衡量。注射前白质不对称性的程度与症状严重程度之间也存在一种趋势关系，但与症状偏侧性、疾病持续时间或既往BTX注射次数无关。分析表明，FA变化至少部分反映了病理生理学的变化，但患者对注射益处的感知与FA变化之间的分离表明，这些变化并未反映肌张力障碍主要“驱动因素”的变化。相比之下，DTI扩散测量没有变化或组间差异，这表明CD中的半球不对称性并不反映不可逆的白质组织损失。这些发现支持了中枢神经系统白质变化参与BTX发挥临床益处机制的假说。
