Limbic encephalitis (LE) is an autoimmune syndrome often associated with temporal lobe epilepsy. Recent research suggests that particular structural changes in LE depend on the type of the associated antibody and occur in both mesiotemporal gray matter and white matter regions. However, it remains questionable to what degree conventional diffusion tensor imaging (DTI)-methods reflect alterations in white matter microstructure, since these methods do not account for crossing fibers. To address this methodological shortcoming, we applied fixel-based analysis as a novel technique modeling distinct fiber populations. For our study, 19 patients with LE associated with autoantibodies against glutamic acid decarboxylase 65 (GAD-LE, mean age = 35.9 years, 11 females), 4 patients with LE associated with autoantibodies against leucine-rich glioma-inactivated 1 (LGI1-LE, mean age = 63.3 years, 2 females), 5 patients with LE associated with contactin-associated protein-like 2 (CASPR2, mean age = 57.4, 0 females), 20 age- and gender-matched control patients with hippocampal sclerosis (19 GAD-LE control patients: mean age = 35.1 years, 11 females; 4 LGI1-LE control patients: mean age = 52.6 years, 2 females; 5 CASPR2-LE control patients: mean age = 42.7 years, 0 females; 10 patients are included in more than one group) and 33 age- and gender-matched healthy control subjects (19 GAD-LE healthy controls: mean age = 34.6 years, 11 females; 8 LGI1-LE healthy controls: mean age = 57.0 years, 4 females, 10 CASPR2-LE healthy controls: mean age = 57.2 years, 0 females; 4 subjects are included in more than one group) underwent structural imaging and DTI at 3 T and neuropsychological testing. Patient images were oriented according to lateralization in EEG resulting in an affected and unaffected hemisphere. Fixel-based metrics fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC = FD · FC) were calculated to retrieve information about white matter integrity both on the micro- and the macroscale. As compared to healthy controls, patients with GAD-LE showed significantly (family-wise error-corrected, p < 0.05) lower FDC in the superior longitudinal fascicle bilaterally and in the isthmus of the corpus callosum. In CASPR2-LE, lower FDC in the superior longitudinal fascicle was only present in the affected hemisphere. In LGI1-LE, we did not find any white matter alteration of the superior longitudinal fascicle. In an explorative tract-based correlation analysis within the GAD-LE group, only a correlation between the left/right ratio of FC values of the superior longitudinal fascicle and verbal memory performance (R = 0.64, Holm-Bonferroni corrected p < 0.048) remained significant after correcting for multiple comparisons. Our results underscore the concept of LE as a disease comprising a broad and heterogeneous group of entities and contribute novel aspects to the pathomechanistic understanding of this disease that may strengthen the role of MRI in the diagnosis of LE.

边缘性脑炎（LE）是一种自身免疫综合征，通常与颞叶癫痫相关。最近的研究表明，LE的特定结构变化取决于相关抗体的类型，并且发生在近颞部灰质和白质区域。但是，传统的扩散张量成像（DTI）方法在多大程度上反映了白质微观结构的变化仍是值得怀疑的，因为这些方法无法解决交叉纤维的问题。为了解决这种方法上的不足，我们将基于Fixel的分析作为一种对不同纤维种群进行建模的新技术。在我们的研究中，有19位LE患者伴有针对谷氨酸脱羧酶65的自身抗体（GAD-LE，平均年龄= 35.9岁，11位女性），多于一组的4名受试者在3 T接受了结构成像和DTI以及神经心理学测试。根据脑电图的偏侧化定向患者图像，受影响和未受影响的半球。计算基于Fixel的指标纤维密度（FD），纤维横截面（FC）以及纤维密度和横截面（FDC = FD·FC），以在微观和宏观尺度上检索有关白质完整性的信息。与健康对照组相比，GAD-LE患者 双侧上纵束和call体峡部的FDC显着降低（按家庭校正），p <0.05。在CASPR2-LE中，上纵束中较低的FDC仅存在于患处半球。在LGI1-LE中，我们没有发现上纵向束的任何白质改变。在GAD-LE组内基于探索性关系的分析中，仅上纵向束的FC值的左右比率与言语记忆能力之间存在相关性（R  = 0.64，Holm-Bonferroni校正后的p  <0.048）更正多个比较后的有效值。我们的结果强调了LE作为一种疾病的概念，该疾病包括广泛而异质的实体，并为该疾病的病理机制理解提供了新的方面，可能会增强MRI在LE诊断中的作用。