Serial CT Myelography in Syringomyelia Patients

脊髓空洞症指的是脊髓内形成的一种充满液体的囊肿，称为空洞。受影响的患者会出现进行性瘫痪。脊髓空洞症最常与Chiari I型畸形有关，在Chiari I型畸形中，小脑扁桃体通过枕大孔异位突出进入椎管。从椎管流出的蛛网膜下腔脑脊液(CSF)受到压缩，在收缩过程中，在部分封闭的脊髓蛛网膜下腔中产生高压波，并压缩传输到脊髓。脊髓空洞症发生和发展的未知机制的一个假说是，囊液积聚是因为在心脏衍生的压力周期中，脑脊液在脊髓细胞外间隙的运动不平衡。通过跟踪脑脊液运动的标记，这一假说可能是可检验的。计算机断层扫描(CT)造影剂异丙咪醇作为替代标记物被检测。对15例Chiari I期患者在Chiari畸形矫正手术前后进行了连续CT脊髓造影检查。手术包括颅颈减压术和硬脑膜成形术，以改善枕大孔区的脑脊液流量。对于脊髓造影术，通过腰椎穿刺点将碘帕咪醇注射到脑脊液中，并在名义上的注射后2、4、6、8、10、22以及少数情况下30和48小时进行C4-C7椎体水平的CT扫描。扫描图像分为蛛网膜下腔(SAS)、脊髓(SC)和脊髓空洞区。每个区域内的灰阶值被空间平均，并以Hounsfield单位记录。使用了三个扫描仪，每个扫描仪都进行了单独校准，以允许从Hounsfield单位转换为异丙咪醇浓度。与预期的增强脑脊液流量一样，手术后异丙咪醇在SAS中的半衰期较短。用经验的二房室药代动力学模型拟合异丙咪醇在SAS和Syrinx的浓度时间曲线，以定量描述这两个区域之间的Iopamidol交换动力学。碘帕咪醇流入和流出脊髓空洞的速率常数之间以及手术前后的平均速率常数之间没有统计学意义上的差异。建立了一个描述这种交换的机制数学模型，该模型假设这种交换是由于异丙咪醇在脊髓组织细胞外扩散而发生的。将测量的SAS、脊髓和脊髓空洞浓度分布与该数学模型预测的分布进行比较，以评估是否可以在不调用除细胞外扩散之外的其他交换机制的情况下解释观察结果。这一比较表明，扩散可能是主要的机制，前提是中间的脊髓是水肿性的，细胞外体积分数从正常组织的约0.2扩大到0.4的数量级。结果表明，需要一个扩散较小的标记物来评估脑脊液通过细胞外空间的对流是否可察觉。

Syringomyelia denotes a fluid-filled cyst, termed a syrinx, that forms in the spinal cord. Affected patients suffer from progressive paralysis. Syringomyelia is most frequently associated with Chiari I malformation in which cerebellar tonsils ectopically protrude through the foramen magnum into the spinal canal. Subarachnoid cerebrospinal fluid (CSF) outflow from the spinal canal is constricted such that, during systole, heightened pressure waves are generated in the partially enclosed spinal subarachnoid space and transmitted compressively to the spinal cord. One hypothesis for the unknown mechanism underlying the development and progression of syringomyelia is that the cyst fluid accumulates because of an imbalance of CSF movement through the spinal cord extracellular space during the cardiac-derived pressure cycles. This hypothesis might be testable by following a marker that tracks the movement of CSF. The computed tomography (CT) contrast agent, iopamidol was tested as a surrogate marker. Serial CT iopamidol myelography was performed in 15 Chiari I patients before and after corrective surgery for the Chiari malformation. The surgery consisted of craniocervical decompression and duraplasty to improve CSF flow at the foramen magnum. For the myelography, iopamidol was injected into the CSF through lumbar punctures and CT scans were obtained at the level of the C4-C7 vertebrae at nominal post-injection times of 2, 4, 6, 8, 10, 22 and, in a few cases, 30 and 48 hrs. The scan images were segmented into subarachnoid space (SAS), spinal cord (SC) and syrinx regions. The gray-scale values within each region were spatially averaged and recorded in Hounsfield units. Three scanners were used and each was individually calibrated to permit conversion from Hounsfield units to iopamidol concentrations. The half-life of iopamidol in the SAS was shorter after surgery as expected for enhanced CSF flow. The time profiles of iopamidol concentration in the SAS and syrinx were fit to simulations from an empirical two-compartment pharmacokinetic model to quantitatively characterize the kinetics of iopamidol exchange between these two regions. There were no statistically significant differences either between the rate constants for iopamidol influx to and efflux from the syrinx or between the preoperative and postoperative mean rate constants. A mechanistic mathematical model was developed to describe the exchange based on the assumption that it occurs as a result of iopamidol diffusion through the extracellular space of the intervening spinal cord tissue. The measured SAS, spinal cord and syrinx concentration profiles were compared to profiles predicted from this mathematical model to assess whether the observations could be explained without invoking other mechanisms for exchange besides extracellular diffusion. The comparison suggested that diffusion could be the predominant mechanism, provided that the intervening spinal cord is edematous with an extracellular volume fraction that is enlarged to the order of 0.4 from a value in normal tissue of about 0.2. The result suggests that a less diffusive marker would be needed for assessing whether CSF convection through the extracellular space is appreciable.