Department of Neurology, Hannover Medical School, Hannover, Germany.
Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany.
PLoS One. 2019 Sep 25;14(9):e0222934. doi: 10.1371/journal.pone.0222934. eCollection 2019.
To investigate cerebral microstructural alterations in patients treated with calcineurin inhibitors (CNI) after orthotopic liver transplantation (OLT) using quantitative magnetic resonance imaging (qMRI) and a cross-sectional study design.
Cerebral qMRI was performed in 85 patients in a median 10 years after OLT compared to 31 healthy controls. Patients were treated with different dosages of CNI or with a CNI-free immunosuppression (CNI-free: n = 19; CNI-low: n = 36; CNI-standard: n = 30). T2-, T2*- and T2'- relaxation times, as well as apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in brain gray and white matter by using the regions of interest method.
In comparison to controls, patients revealed significantly increased T2, T2*, T2', ADC and reduced FA, predominantly in the frontal white matter, indicating microstructural brain alterations represented by increased free water (increased T2), reduced neuronal metabolism (increased T2') and a lower degree of spatial organization of the nervous fibers (reduced FA). CNI-low and CNI-free patients showed more alterations than CNI-standard patients. Analysis of their history revealed impairment of kidney function while under standard CNI dose suggesting that these patients may be more vulnerable to toxic CNI side-effects.
Our findings suggest that the individual sensitivity to toxic side effects should be considered when choosing an appropriate immunosuppressive regimen in patients after liver transplantation.
采用定量磁共振成像（qMRI）和横断面研究设计，研究接受钙调神经磷酸酶抑制剂（CNI）治疗的原位肝移植（OLT）后患者的脑微观结构改变。
对 85 例 OLT 后中位数为 10 年的患者进行脑 qMRI 检查，并与 31 名健康对照进行比较。患者接受不同剂量的 CNI 或无 CNI 免疫抑制治疗（CNI 无：n=19；CNI 低：n=36；CNI 标准：n=30）。采用感兴趣区法测量脑灰质和白质的 T2、T2*、T2'弛豫时间以及表观扩散系数（ADC）和各向异性分数（FA）。
与对照组相比，患者的 T2、T2*、T2'、ADC 显著增加，FA 显著降低，主要位于额叶白质，表明存在以自由水增加（T2 增加）、神经元代谢减少（T2'增加）和神经纤维空间组织程度降低（FA 降低）为特征的脑微观结构改变。CNI 低和 CNI 无患者的改变比 CNI 标准患者更明显。对其病史的分析显示，在接受标准 CNI 剂量时肾功能受损，这表明这些患者可能更容易受到 CNI 毒性副作用的影响。
我们的研究结果表明，在选择肝移植后患者的适当免疫抑制方案时，应考虑个体对毒性副作用的敏感性。
