Department of Diagnostic Radiology, Division of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea.
Brain. 2011 Apr;134(Pt 4):1199-210. doi: 10.1093/brain/awr021. Epub 2011 Mar 7.
Periventricular leucomalacia has long been investigated as a leading cause of motor and cognitive dysfunction in patients with spastic diplegic cerebral palsy. However, patients with periventricular leucomalacia on conventional magnetic resonance imaging do not always have motor dysfunction and preterm children without neurological abnormalities may have periventricular leucomalacia. In addition, it is uncertain whether descending motor tract or overlying cortical injury is related to motor impairment. To investigate the relationship between motor pathway injury and motor impairment, we conducted voxelwise correlation analysis using tract-based spatial statistics of white matter diffusion anisotropy and voxel-based-morphometry of grey matter injury in patients with periventricular leucomalacia and spastic diplegia (n = 43, mean 12.86 ± 4.79 years, median 12 years). We also evaluated motor cortical and thalamocortical connectivity at resting state in 11 patients using functional magnetic resonance imaging. The functional connectivity results of patients with spastic diplegic cerebral palsy were compared with those of age-matched normal controls. Since γ-aminobutyric acid(A) receptors play an important role in the remodelling process, we measured neuronal γ-aminobutyric acid(A) receptor binding potential with dynamic positron emission tomography scans (n = 27) and compared the binding potential map of the patient group with controls (n = 20). In the current study, white matter volume reduction did not show significant correlation with motor dysfunction. Although fractional anisotropy within most of the major white matter tracts were significantly lower than that of age-matched healthy controls (P < 0.05, family wise error corrected), fractional anisotropy mainly within the bilateral corticospinal tracts and posterior body and isthmus of the corpus callosum showed more significant correlation with motor dysfunction (P < 0.03) than thalamocortical pathways (P < 0.05, family-wise error corrected). Cortical volume of the pre- and post-central gyri and the paracentral lobule tended to be negatively correlated with motor function. The motor cortical connectivity was diminished mainly within the bilateral somatosensory cortex, paracentral lobule, cingulate motor area and visual cortex in the patient group. Thalamovisual connectivity was not diminished despite severe optic radiation injury. γ-Aminobutyric acid(A) receptor binding potential was focally increased within the lower extremity homunculus, cingulate cortex, visual cortex and cerebellum in the patient group (P < 0.05, false discovery rate corrected). In conclusion, descending motor tract injury along with overlying cortical volume reduction and reduced functional connectivity appears to be a leading pathophysiological mechanism of motor dysfunction in patients with periventricular leucomalacia. Increased regional γ-aminobutyric acid(A) receptor binding potential appears to result from a compensatory plasticity response after prenatal brain injury.
脑白质软化症一直被认为是痉挛性双瘫脑瘫患者运动和认知功能障碍的主要原因。然而，常规磁共振成像上有脑白质软化症的患者并不总是有运动功能障碍，没有神经异常的早产儿也可能有脑白质软化症。此外，尚不确定下行运动束或皮质损伤与运动障碍有关。为了研究运动通路损伤与运动障碍的关系，我们使用弥散张量成像的束内空间统计学和脑灰质损伤的体素形态计量学对脑白质软化症合并痉挛性双瘫患者（n=43，平均 12.86±4.79 岁，中位数 12 岁）进行了体素相关分析。我们还使用功能磁共振成像对 11 例痉挛性双瘫患者进行了静息状态下运动皮质和丘脑皮质连接的评估。将痉挛性双瘫脑瘫患者的功能连接结果与年龄匹配的正常对照组进行比较。由于γ-氨基丁酸（A）受体在重塑过程中起着重要作用，我们使用动态正电子发射断层扫描（n=27）测量了神经元γ-氨基丁酸（A）受体结合势，并将患者组的结合势图与对照组（n=20）进行了比较。在本研究中，脑白质体积减少与运动功能障碍无显著相关性。尽管大多数主要白质束的各向异性分数明显低于年龄匹配的健康对照组（P<0.05，经家族错误校正），但双侧皮质脊髓束和胼胝体体部和后连合的各向异性分数与运动功能障碍的相关性（P<0.03）明显大于丘脑皮质通路（P<0.05，经家族错误校正）。中央前回和中央后回以及旁中央小叶的皮质体积与运动功能呈负相关。患者组的运动皮质连接主要在双侧感觉皮质、旁中央小叶、扣带回运动区和视觉皮质内减弱。尽管视辐射严重损伤，但丘脑-视觉连接并未减弱。γ-氨基丁酸（A）受体结合势在患者组的下肢同身像、扣带回皮质、视觉皮质和小脑内呈局灶性升高（P<0.05，经假发现率校正）。总之，下行运动束损伤以及皮质下体积减少和功能连接减少似乎是脑白质软化症患者运动功能障碍的主要病理生理机制。产前脑损伤后的代偿性可塑性反应导致局部γ-氨基丁酸（A）受体结合势增加。
