Zimmer W E, Hourihane J M, Wang H Z, Schriber J R
Department of Radiology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
AJNR Am J Neuroradiol. 1998 Apr;19(4):601-8; discussion 609-10.
We examined the relationship between human leukocyte antigen (HLA) matching and the development of cyclosporine (CyA) neurotoxicity in patients undergoing allogeneic bone marrow transplantation, and determined the frequency and imaging characteristics of CyA neurotoxicity in these patients.
Records of 87 patients who underwent allogeneic bone marrow transplantation were reviewed. Eight patients who presented with visual disturbance and/or seizures and had MR imaging within 24 hours were identified. Transplant donor relatedness was examined, and patients' imaging studies were reviewed. Clinical parameters, including blood pressure, CyA, creatinine, and magnesium levels, and the presence of graft-versus-host disease were reviewed.
CyA neurotoxicity was seen more frequently in HLA-mismatched and unrelated donor transplants. The frequency of CyA neurotoxicity was 4% for patients with a 5/6 or 6/6 HLA match, 13% for matched unrelated donor transplants, and 50% for haplotypic 3/6 or 4/6 transplants. Patients with matched unrelated donor transplants and haplotypic transplants presented earlier in the posttransplant time course and had decreased survival time relative to patients with HLA-matched transplants. Imaging abnormalities most commonly affected the occipital lobes and the posterior cerebral hemispheres; both cortical and white matter involvement was identifiable as T1 hypointense and T2 hyperintense signal with associated gyral swelling and sulcal effacement on the initial MR studies. Hypodensity in the affected areas was noted on CT scans. Contrast enhancement was seen in HLA-mismatched and unrelated transplants only. Follow-up imaging showed interval decreases in subcortical edema; however, residual signal abnormality, primarily affecting the cortex, was present in all cases and seen best on proton density-weighted MR images.
The frequency of severe CyA neurotoxicity increases with increasing HLA disparity, suggesting that immune factors may play a role. CyA neurotoxicity appears to represent a spectrum of disease processes. Disruption of the blood-brain barrier as well as hypoxic or vasculitic cortical injury resulting in MR-detectable cortical signal abnormalities may occur in severe cases.
我们研究了接受异基因骨髓移植患者的人类白细胞抗原（HLA）匹配与环孢素（CyA）神经毒性发生之间的关系，并确定了这些患者中CyA神经毒性的发生率及影像学特征。
回顾了87例接受异基因骨髓移植患者的记录。确定了8例出现视觉障碍和/或癫痫发作且在24小时内进行了磁共振成像（MR）检查的患者。检查了移植供体的相关性，并对患者的影像学研究进行了回顾。回顾了临床参数，包括血压、CyA、肌酐和镁水平，以及移植物抗宿主病的存在情况。
CyA神经毒性在HLA不匹配和无关供体移植中更常见。HLA 5/6或6/6匹配的患者中CyA神经毒性的发生率为4%，匹配无关供体移植患者为13%，单倍型3/6或4/6移植患者为50%。与HLA匹配移植的患者相比，匹配无关供体移植和单倍型移植的患者在移植后的病程中出现得更早，生存时间缩短。影像学异常最常累及枕叶和大脑后半球；在最初的MR研究中，皮质和白质受累均表现为T1低信号和T2高信号，伴有脑回肿胀和脑沟消失。CT扫描显示受累区域密度减低。仅在HLA不匹配和无关供体移植中可见对比增强。随访影像学显示皮质下水肿逐渐减轻；然而，所有病例均存在主要影响皮质的残留信号异常，在质子密度加权MR图像上显示最佳。
严重CyA神经毒性的发生率随着HLA差异的增加而升高，提示免疫因素可能起作用。CyA神经毒性似乎代表了一系列疾病过程。在严重病例中可能发生血脑屏障破坏以及缺氧或血管炎性皮质损伤，导致MR可检测到的皮质信号异常。
