Serial CT Myelography in Syringomyelia Patients

脊髓空洞症是指在脊髓内形成的充满液体的囊肿，称为脊髓空洞。受影响的患者会出现进行性瘫痪。脊髓空洞最常与Chiari I型畸形相关，其中小脑扁桃体通过枕骨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）被压缩，因此在收缩期，在部分封闭的脊髓蛛网膜下腔中产生增高的压力波，并压迫性地传递到脊髓。一种关于脊髓空洞发生和发展的未知机制的假设是，在心源性压力循环中，脑脊液通过脊髓细胞外空间运动的不平衡导致囊肿液积累。这个假设可以通过追踪脑脊液运动的标记来验证。计算机断层扫描（CT）造影剂，iopamidol测试作为替代标志物。对15例Chiari I型患者进行了Chiari畸形矫正手术前后的连续CT iopamidol脊髓造影检查。手术包括颅颈减压和硬脑膜成形术，以改善枕骨大孔处的脑脊液流动。对于脊髓造影，通过腰椎穿刺将iopamidol注射到脑脊液中，并在注射后2、4、6、8、10、22以及少数病例30和48小时的名义时间在C4-C7椎体水平上进行CT扫描。扫描图像被分割为蛛网膜下腔区（SAS）、脊髓区（SC）和喉区。每个区域内的灰度值被空间平均并以Hounsfield单位记录。使用了三个扫描仪，每个扫描仪都单独校准，以允许从霍斯菲尔德单位转换为iopamidol浓度。手术后，由于脑脊液血流增强，异帕美在SAS中的半衰期缩短。利用经验双室药代动力学模型模拟了SAS和syrinx中iopamidol浓度的时间分布，定量表征了这两个区域之间的iopamidol交换动力学。无论是注射管内流和流出的速率常数，还是术前和术后平均速率常数，均无统计学上的显著差异。我们建立了一个机制数学模型来描述这种交换，该模型基于一种假设，即这种交换是由于iopamidol通过中间脊髓组织的细胞外空间扩散而发生的。将测量到的SAS、脊髓和注射器浓度曲线与该数学模型预测的曲线进行比较，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。比较表明，扩散可能是主要机制，前提是中间脊髓水肿，细胞外体积分数从正常组织的约0.2增加到0.4左右。结果表明，需要一种弥漫性较小的标记物来评估脑脊液通过细胞外空间的对流是否明显。

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.