Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease with an incidence rate of approximately 10 per 100,000 patient years in the general population. It has an associated mortality rate of about 35% in N. America with less than one third afflicted making a full recovery. Sadly despite the recent medical advances, the long-term prognosis has not improved significantly. Historically, the vasospasm was the culprit to explain these deficits. However, despite reduction of the incidence of vasospasm, the outcome was not changed. Thus, it is becoming clear that early events after the SAH are crucial on the death of neurons that will lead to the altered functional status of these patients. However, the exact nature of this early injury and the nature of the immune activation are ill defined.
Methods: In order to decipher the immune phenotype of sub-arachnoid haemorrhage patients, we collected blood and CSF (when available) at admission, and days 1, 2, 5, and 10. After leukocyte isolation, using multicolor flow cytometry, the leukocyte phenotype was determined. 40 soluble molecules were measured in sera and CSF with a multiplex platform.
Results: Using our novel translational clinical immunomonitoring platform, we highlighted an immunological signature present in the blood and in the cerebral spinal fluid of 14 patients with aSAH. We observed an early presence of inflammatory monocytes associated with a late activation of lymphocytes. Furthermore, analyses of plasma and cerebral spinal fluid, we saw temporal distinctions in the profiles of monocytic trophic factors (early) compared to vascular and lymphocytic factors (late).
Conclusions: Our platform will help us to decipher the interactions between the leukocyte activation and vascular inflammation in relationship to morbidity and neuronal cell death. This project highlighted novel immunological targets that could be manipulated pharmacologically to improve the clinical outcomes of this patient population in need.
Patient Care: We will highlight an immunological signature associated with worst outcome that will open the way to new immunomodulatory treatments aimed at reducing neuronal cell death in this patient population.
Learning Objectives: By the conclusion of this session, participants should be able to:
1) Describe the importance of early brain injury in the outcome of SAH patients
2) Discuss the immune activation following SAH.
3) Identify potential immunological targets for these patients.