Department of Neuroradiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Neurology and Clinical Neuroscience, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Brain. 2022 Sep 14;145(9):3203-3213. doi: 10.1093/brain/awac045.
While neuropathological examinations in patients who died from COVID-19 revealed inflammatory changes in cerebral white matter, cerebral MRI frequently fails to detect abnormalities even in the presence of neurological symptoms. Application of multi-compartment diffusion microstructure imaging (DMI), that detects even small volume shifts between the compartments (intra-axonal, extra-axonal and free water/CSF) of a white matter model, is a promising approach to overcome this discrepancy. In this monocentric prospective study, a cohort of 20 COVID-19 inpatients (57.3 ± 17.1 years) with neurological symptoms (e.g. delirium, cranial nerve palsies) and cognitive impairments measured by the Montreal Cognitive Assessment (MoCA test; 22.4 ± 4.9; 70% below the cut-off value <26/30 points) underwent DMI in the subacute stage of the disease (29.3 ± 14.8 days after positive PCR). A comparison of whole-brain white matter DMI parameters with a matched healthy control group (n = 35) revealed a volume shift from the intra- and extra-axonal space into the free water fraction (V-CSF). This widespread COVID-related V-CSF increase affected the entire supratentorial white matter with maxima in frontal and parietal regions. Streamline-wise comparisons between COVID-19 patients and controls further revealed a network of most affected white matter fibres connecting widespread cortical regions in all cerebral lobes. The magnitude of these white matter changes (V-CSF) was associated with cognitive impairment measured by the MoCA test (r = -0.64, P = 0.006) but not with olfactory performance (r = 0.29, P = 0.12). Furthermore, a non-significant trend for an association between V-CSF and interleukin-6 emerged (r = 0.48, P = 0.068), a prominent marker of the COVID-19 related inflammatory response. In 14/20 patients who also received cerebral 18F-FDG PET, V-CSF increase was associated with the expression of the previously defined COVID-19-related metabolic spatial covariance pattern (r = 0.57; P = 0.039). In addition, the frontoparietal-dominant pattern of neocortical glucose hypometabolism matched well to the frontal and parietal focus of V-CSF increase. In summary, DMI in subacute COVID-19 patients revealed widespread volume shifts compatible with vasogenic oedema, affecting various supratentorial white matter tracts. These changes were associated with cognitive impairment and COVID-19 related changes in 18F-FDG PET imaging.
在死于 COVID-19 的患者的神经病理学检查中发现了大脑白质的炎症变化，但即使存在神经症状，脑 MRI 也经常未能检测到异常。应用多室扩散微观结构成像 (DMI)，可以检测到白质模型各室（轴内、轴外和自由水/CSF）之间的微小容积变化，是克服这一差异的有前途的方法。在这项单中心前瞻性研究中，一组 20 名 COVID-19 住院患者（57.3 ± 17.1 岁）出现神经系统症状（例如谵妄、颅神经麻痹）和认知障碍，通过蒙特利尔认知评估（MoCA 测试）进行测量（22.4 ± 4.9；低于 26/30 分的临界值<70%），在疾病的亚急性期（PCR 阳性后 29.3 ± 14.8 天）进行 DMI。将整个大脑白质 DMI 参数与匹配的健康对照组（n=35）进行比较，发现从轴内和轴外空间到自由水部分（V-CSF）的容积转移。这种与 COVID 相关的广泛 V-CSF 增加影响了整个大脑皮质的上矢状突白质，额区和顶区达到最大值。COVID-19 患者与对照组之间的流线比较进一步显示出连接所有大脑叶皮质广泛区域的受影响最严重的白质纤维网络。这些白质变化（V-CSF）的程度与 MoCA 测试测量的认知障碍相关（r=-0.64，P=0.006），但与嗅觉表现无关（r=0.29，P=0.12）。此外，V-CSF 与白细胞介素-6 之间存在关联的趋势，但无统计学意义（r=0.48，P=0.068），白细胞介素-6 是 COVID-19 相关炎症反应的一个突出标志物。在 20 名接受大脑 18F-FDG PET 检查的患者中，14 名患者 V-CSF 增加与先前定义的 COVID-19 相关代谢空间协变模式的表达相关（r=0.57；P=0.039）。此外，新皮质葡萄糖代谢低下的额顶优势模式与 V-CSF 增加的额区和顶区焦点非常吻合。总之，亚急性 COVID-19 患者的 DMI 显示出与血管源性水肿一致的广泛容积转移，影响各种大脑皮质上矢状突白质束。这些变化与认知障碍和 COVID-19 相关的 18F-FDG PET 成像变化有关。
