Sepsis-Associated Encephalopathy: From Delirium to Dementia?

Abstract

Sepsis is a major cause of death in intensive care units worldwide. The acute phase of sepsis is often accompanied by sepsis-associated encephalopathy, which is highly associated with increased mortality. Moreover, in the chronic phase, more than 50% of surviving patients suffer from severe and long-term cognitive deficits compromising their daily quality of life and placing an immense burden on primary caregivers. Due to a growing number of sepsis survivors, these long-lasting deficits are increasingly relevant. Despite the high incidence and clinical relevance, the pathomechanisms of acute and chronic stages in sepsis-associated encephalopathy are only incompletely understood, and no specific therapeutic options are yet available. Here, we review the emergence of sepsis-associated encephalopathy from initial clinical presentation to long-term cognitive impairment in sepsis survivors and summarize pathomechanisms potentially contributing to the development of sepsis-associated encephalopathy.

Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms

“…Notably, blood plasma levels of pro-inflammatory cytokines (e.g., Neuropsychiatric sequelae of COVID-19 6 interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, IL-8, IL-10, IL-2R) were significantly higher among fatal COVID-19 cases, indicative of hypercytokinemia, or "cytokine storm syndrome," which was also reported in SARS-CoV-1 (Huang et al, 2005), and may underlie encephalopathy. Beyond the acute effects of cytokine storm, a recent meta-analysis of delirium among intensive care patients of mixed conditions reported evidence of persistent neurocognitive deficits up to 18 months post-discharge (Salluh et al, 2015), including mild cognitive impairment (Chung et al, 2020). Given other emerging evidence of hypercytokinemia in hospitalized COVID-19 patients , the burden of long-term post-SARS-CoV-2 delirium may be significant, particularly for elderly patients who are more susceptible to post-infectious neurocognitive complications.…”

Psychiatric face of COVID-19

“…Indeed, a study of neuropsychiatric consequences of SARS-COV-1 performed at 30-50 months after the infection demonstrated an occurrence of 40% of posttraumatic stress disorder (PTSD), 36.4% of depression, 15.6% of obsessive convulsive disorder, and an equal incidence for anxiety disorders 78 . Furthermore, a metaanalysis among SARS-COV-1 patients of mixed conditions showed neurocognitive deficits up to 18 months post-discharge 79 , including mild cognitive impairment 80 .…”

Neuroinvasion of SARS‐CoV‐2 may play a role in the breakdown of the respiratory center of the brain

“…Elevated pro‐inflammatory cytokine titer in affected patients' blood plasma had been suggested to be significantly responsible for the aggravation of COVID‐19 symptoms and its associated morbidities 66 . “Hypercytokinemia” or “cytokine storm” can also lead to CNS inflammation with the occurrence of fever, CNS pleocytosis, encephalitis, delirium, and cognitive impairment, which are common in some intensive/critical care unit patients of COVID‐19 67 …”

“…66 "Hypercytokinemia" or "cytokine storm" can also lead to CNS inflammation with the occurrence of fever, CNS pleocytosis, encephalitis, delirium, and cognitive impairment, which are common in some intensive/critical care unit patients of COVID-19. 67…”