Background

Progressive cognitive decline following multimodal neurooncological treatment is a common observation in patients suffering from malignant glioma. Alterations of the default-mode network (DMN) represent a possible source of impaired neurocognitive functioning and were analyzed in these patients.

Methods

Eighty patients (median age, 51 years) with glioma (WHO grade IV glioblastoma, n = 57; WHO grade III anaplastic astrocytoma, n = 13; WHO grade III anaplastic oligodendroglioma, n = 10) and ECOG performance score 0–1 underwent resting-state functional MRI (rs-fMRI) and neuropsychological testing at a median interval of 13 months (range, 1–114 months) after initiation of therapy. For evaluation of structural and metabolic changes after treatment, anatomical MRI and amino acid PET using O-(2-[¹⁸F]fluoroethyl)-L-tyrosine (FET) were simultaneously acquired to rs-fMRI on a hybrid MR/PET scanner. A cohort of 80 healthy subjects matched for gender, age, and educational status served as controls.

Results

The connectivity pattern within the DMN (12 nodes) of the glioma patients differed significantly from that of the healthy subjects but did not depend on age, tumor grade, time since treatment initiation, presence of residual/recurrent tumor, number of chemotherapy cycles received, or anticonvulsive medication. Small changes in the connectivity pattern were observed in patients who had more than one series of radiotherapy. In contrast, structural tissue changes located at or near the tumor site (including resection cavities, white matter lesions, edema, and tumor tissue) had a strong negative impact on the functional connectivity of the adjacent DMN nodes, resulting in a marked dependence of the connectivity pattern on tumor location. In the majority of neurocognitive domains, glioma patients performed significantly worse than healthy subjects. Correlation analysis revealed that reduced connectivity in the left temporal and parietal DMN nodes was associated with low performance in language processing and verbal working memory. Furthermore, connectivity of the left parietal DMN node also correlated with processing speed, executive function, and verbal as well as visual working memory. Overall DMN connectivity loss and cognitive decline were less pronounced in patients with higher education.

Conclusion

Personalized treatment strategies for malignant glioma patients should consider the left parietal and temporal DMN nodes as vulnerable regions concerning neurocognitive outcome.

中文翻译：

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多模式治疗后默认模式静息态网络对恶性胶质瘤患者认知功能的作用。

背景

多模式神经肿瘤治疗后进行性认知能力下降是恶性神经胶质瘤患者的常见现象。默认模式网络（DMN）的改变代表了神经认知功能受损的可能根源，并在这些患者中进行了分析。

方法

80 名神经胶质瘤患者（中位年龄 51 岁）（WHO IV 级胶质母细胞瘤，n = 57；WHO III 级间变性星形细胞瘤，n = 13；WHO III 级间变性少突胶质细胞瘤，n = 10）且 ECOG 表现评分为 0-1，接受了静息治疗开始后，中位间隔 13 个月（范围 1-114 个月）进行状态功能 MRI (rs-fMRI) 和神经心理学测试。^{为了评估治疗后的结构和代谢变化，使用 O-(2-[ 18} F]氟乙基)-L-酪氨酸 (FET)的解剖 MRI 和氨基酸 PET在混合 MR/PET 扫描仪上同时采集到 rs-fMRI。由 80 名性别、年龄和教育状况相匹配的健康受试者组成的队列作为对照。

结果

神经胶质瘤患者的 DMN（12 个节点）内的连接模式与健康受试者显着不同，但不依赖于年龄、肿瘤分级、治疗开始后的时间、残留/复发肿瘤的存在、接受的化疗周期数、或抗惊厥药物。在接受过一系列以上放疗的患者中观察到连接模式的微小变化。相反，位于或靠近肿瘤部位的结构组织变化（包括切除空洞、白质病变、水肿和肿瘤组织）对邻近DMN节点的功能连接产生强烈的负面影响，导致对DMN节点的显着依赖性。肿瘤位置的连接模式。在大多数神经认知领域，神经胶质瘤患者的表现明显差于健康受试者。相关分析显示，左颞叶和顶叶 DMN 节点的连通性降低与语言处理和言语工作记忆的低表现有关。此外，左顶叶 DMN 节点的连接性还与处理速度、执行功能、言语和视觉工作记忆相关。受过高等教育的患者总体 DMN 连接性丧失和认知能力下降不太明显。

结论

恶性胶质瘤患者的个性化治疗策略应将左侧顶叶和颞侧 DMN 节点视为神经认知结果的脆弱区域。