Spontaneous Aneurysmal Subarachnoid Hemorrhage and Related Cortisol and Immunologic Alterations: Impact on Patients' Health-related Quality of Life

Abstract

Objective To highlight the impact of aneurysmal subarachnoid hemorrhage (SAH) on surviving patients' health-related quality of life (HRQoL) with respect to cortisol and interleukin (IL)-6 alterations and also to identify possible clinical predictors for a better HRQoL. Methods Fifty surviving patients treated in our hospital for aneurysmal SAH in a 2-year period with sufficient HRQoL data were enrolled. A good clinical outcome was represented by the modified Rankin Scale (mRS) 0 to 2. The patient's HRQoL was assessed using the Short Form health survey questionnaire, the Beck Depression Inventory, and the Daily Fatigue Impact Scale at 6 and 12 months. The results were analyzed regarding possible correlation to 24-hour urinary free cortisol, serum, and cerebrospinal fluid IL-6 levels. Results A reduction of HRQoL in up to 35% of survivors was observed at 6 months and in a high proportion of patients (47.2%) with an assumable good outcome (mRS 0–2). Reduced HRQoL in survivors was found in terms of SF-36 (34.9%), depression (26.8%), and fatigue (14%) at 6 months and 18.4%, 39.4%, and 18.9% at 12 months, respectively. Improvement was recorded at 12 months, mainly in SF-36. Early elevated 24-hour urinary free cortisol and IL-6 levels showed a significant positive impact on HRQoL. Conclusions Early cortisol and IL-6 levels may predict patients' HRQoL after SAH. Twelve months after SAH, a considerable percentage of patients with a presumably good outcome (mRS 0–2) had a lower HRQoL compared with the general population. Implementing corresponding tests at discharge and 12-month follow-up is recommended.

Interleukin 6 in cerebrospinal fluid is a biomarker for delayed cerebral ischemia (DCI) related infarctions after aneurysmal subarachnoid hemorrhage

“…This explains why CSF IL-6 levels were higher in patients with an adverse outcome in our study, since the occurrence of secondary infarcts is a major negative outcome predictor 9 , 11 , 46 . Very similar findings have also been reported by other groups 5 , 28 , 31 , 32 , 34 . However, possible associations of IL-6 levels with the severity of the bleed and other outcome relevant parameters also warrant consideration.…”

“…The pathophysiology of DCI and secondary infarction remains unclear, but the inflammatory response elicited by a cerebral hemorrhage may play a significant pathogenetic role. This has prompted several groups to investigate IL-6 which is one of the more prominent proinflammatory cytokines as a biomarker for DCI 5 , 28 , 30 – 32 , 34 , 41 , 42 . The present study has two principal findings.…”

“…Indeed, IL-6 levels have been prominently discussed as potential biomarkers for ischemic stroke risk, outcome after stroke and even infarct size 43 – 45 . Most investigators have analyzed serum but a few also CSF IL-6 levels 28 , 30 , 32 , 34 , 41 , 42 . Importantly, these data underline the role of neuroinflammation in the pathophysiology of DCI.…”

“…IL-6 levels in CSF and serum [pg/ml] were obtained per routine (Electrochemiluminescence immunoassay; ELECSYS IL6, Roche Diagnostics GmbH, Mannheim, Germany) directly after a CSF drain was placed and daily thereafter until the drain was removed. VS is most often seen between days 4 and 14 following SAH, and several groups investigating a possible link between IL-6 levels and vasospasm have hence focused on day 4 to 14 IL-6 findings 5 , 28 , 29 , 34 , 39 . For the purposes of our analysis we have therefore studied day 0–3 and 4–14 CSF IL-6 peak values separately in addition to overall CSF and serum peaks (day 0–28).…”

“…Several investigators have therefore analyzed IL-6 levels in SAH patients, and some studies describe a correlation between elevated IL-6 levels and DCI 5 , 19 , 20 , 28 – 33 . IL-6 levels may correlate with the patients’ health related quality of life (HRQoL) 34 .…”