Autonomic nervous system shift – infections-intracerebral hemorrhage
A report in the journal Stroke indicates that a sympathetic nervous system over-activity and predominance is associated with higher rate of infection following acute intracerebral hemorrhage (ICH).
Stroke is a major cause of morbidity and the third leading cause of death in the Western world. Infections occur commonly following stroke and adversely influence outcome. Pulmonary and urinary infections are the most frequent medical complications after stroke and the leading cause of death.
The neuroendocrine and immune mechanisms leading to high occurrence of infections after stroke remain poorly understood. Emerging research suggests that infections early after stroke could be the manifestation of a stroke-induced immunodepression syndrome, which is now recognized as an independent factor associated with increased susceptibility.
Th2-related cytokines such as IL-10 exert potent immunosuppressive effects, and previous research has shown that the ‘sympathetic storm’-induced IL-10 release due to acute accidental or iatrogenic brain trauma may cause “brain-mediated” immunodepression and subsequent infections (Woiciechowsky et al., 1998). More recent studies indicate a strong association between high catecholamine levels and poststroke infections in patients with acute ischemic stroke.
In the Stroke study, Marek Sykora and colleagues from the Department of Neurology, University of Heidelberg, Heidelberg, Germany, investigated the role of autonomic shift in increased susceptibility to infection after acute intracerebral hemorrhage (ICH).
The authors report that an autonomic shift toward SNS predominance is independently linked to higher occurrence of infection after ICH.
This, and previous studies indicate that the sympathetic activation may play a central role in the immunodepression associated with central nervous system injury. The authors discuss that the occurrence of bacterial infections after stroke can be prevented by administration of beta-blockers, in animal studies, while in humans, in a recent retrospective study, stroke patients with beta-blocker treatment less often had stroke-related pneumonia.
Thus, according to the authors, the modulation of autonomic nervous system function, alone or in combination with prophylactic antibiotic treatment, may represent an attractive therapeutic option in preventing infective complications after stroke.
SOURCE: Stroke 2011, 42:1218. Epub 2011 Mar 10. Read more:
A 2012 reviewdiscuss some major mechanism and factors that may help in predicting post-stroke infections. As per the authors of this review, stroke or traumatic brain injury, disturbs the normally well-balanced interplay between the nervous and the immune system by compromising sympathetic and parasympathetic neural connections with lymphoid organs. They highlight the importance of a 2007 study by Chamorro et al. demonstrated that the development of infections early after acute ischaemic stroke is associated with enhanced activation of the sympathetic adrenomedullar pathway as indicated by significantly increased plasma catecholamine levels on day 1 after stroke in patients who subsequently (days 2–7) developed infections.
In summary, according to the authors, changes in immune and stress markers that occur very early after stroke onset, explain the high susceptibility of stroke patients to bacterial infections, and are able to predict infectious complications occurring within 2 weeks after stroke. Yet, so far, only two blood-based biomarkers have been identified as independent predictors of outcome and mortality after stroke: the stress marker copeptin and midregional pro-atrial natriuretic peptide.
The authors concluded that blood-based immune and stress markers might identify patients at high risk of post-stroke infections as well as patients with unfavourable outcomes.
A 2013 studyreports that (1) only large ischemic and hemorrhagic strokes lead to increased plasma levels of some catecholamine metabolites and cortisol. (2) Extensive lesions are associated with pronounced lymphocytopenia, increased cytokine secretion and a strong acute phase reaction. (3) Signs of bacterial infection including positive culture results or elevated hsPCT increase after cerebrovascular events. (4) Catecholamine and steroid levels were neither independent predictors of lymphocytopenia nor of bacterial infection.
Thus, this study challenges the concept of stress hormone mediated immunodepression after ischemic and hemorrhagic stroke. Stroke severity and lymphocyte number may serve as valuable predictors for early stratification of patients for antibiotic treatment.
A 2019 study prospectively analyzed patients with acute ischemic stroke. ANS was measured using the cross-correlational baroreflex sensitivity (BRS) at admission. The occurrence and cause of in-hospital infections was assessed based on the clinical and laboratory examination. The study found patients with infections had significantly lower BRS.
Of note, previous data have demonstrated that BRS is attenuated whenever sympathetic nervous system activity is enhanced. The authors of this study concluded that decreased BRS was independently associated with infections after ischemic stroke. Autonomic shift may play an important role in increased susceptibility to infections after stroke.
Another 2019 study reports that the high-BRS group had lower rates of complications and stroke recurrence compared to the low-BRS group. The authors of this study found that in contrast to no incidence of acute ischemic stroke (AIS) in patients with high BRS, 10% of the patients with low BRS developed pneumonia and UTI during hospitalization. These data are comparable to the reports in the literature and indicate BRS as an independent predictor for complications of pneumonia and UTI during hospitalization.