Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Nat Rev Immunol. 2022 Jul;22(7):444-458. doi: 10.1038/s41577-021-00643-7. Epub 2021 Nov 11.
Systemic inflammation elicited by sepsis can induce an acute cerebral dysfunction known as sepsis-associated encephalopathy (SAE). Recent evidence suggests that SAE is common but shows a dynamic trajectory over time. Half of all patients with sepsis develop SAE in the intensive care unit, and some survivors present with sustained cognitive impairments for several years after initial sepsis onset. It is not clear why some, but not all, patients develop SAE and also the factors that determine the persistence of SAE. Here, we first summarize the chronic pathology and the dynamic changes in cognitive functions seen after the onset of sepsis. We then outline the cerebral effects of sepsis, such as neuroinflammation, alterations in neuronal synapses and neurovascular changes. We discuss the key factors that might contribute to the development and persistence of SAE in older patients, including premorbid neurodegenerative pathology, side effects of sedatives, renal dysfunction and latent virus reactivation. Finally, we postulate that some of the mechanisms that underpin neuropathology in SAE may also be relevant to delirium and persisting cognitive impairments that are seen in patients with severe COVID-19.
脓毒症引起的全身炎症可引发急性脑功能障碍，即脓毒症相关性脑病（SAE）。最近的证据表明，SAE 很常见，但随时间呈动态变化。在重症监护病房中，一半的脓毒症患者会发生 SAE，一些幸存者在初始脓毒症发作后数年仍存在持续的认知障碍。目前尚不清楚为什么有些患者会发生 SAE，而不是所有患者，也不清楚是什么因素决定了 SAE 的持续存在。在这里，我们首先总结了脓毒症发作后出现的慢性病理学和认知功能的动态变化。然后，我们概述了脓毒症对大脑的影响，如神经炎症、神经元突触的改变和神经血管变化。我们讨论了可能导致老年患者发生和持续 SAE 的关键因素，包括潜在的神经退行性病理、镇静剂的副作用、肾功能障碍和潜伏病毒再激活。最后，我们推测，SAE 神经病理学的一些机制可能与严重 COVID-19 患者出现的谵妄和持续认知障碍也有关。
