Clinical StudyCerebral inflammatory response and predictors of admission clinical grade after aneurysmal subarachnoid hemorrhage
Introduction
Aneurysmal subarachnoid hemorrhage (aSAH) affects nearly 30 000 individuals each year in the United States.[1], [2] Although early surgical and neuroendovascular interventions, as well as aggressive postoperative management strategies, have improved outcomes, mortality in the acute phase following aneurysm rupture is significant: 12% of aSAH patients die within the first 24 hours and 25% within the first 48 hours.3 Early brain injury (EBI) is a recently coined term that describes the immediate injury to the brain after aneurysm rupture and the response to hemorrhage within the subarachnoid space.[4], [5], [6], [7], [8], [9] A number of critical, interrelated pathways have been implicated in EBI, including apoptotic mechanisms and ischemic pathways, which lead to neuronal cell death, cerebral edema, and a global cerebral inflammatory process.[6], [7], [10] This early inflammatory response may underlie the host of metabolic, hormonal, neuronal, and vascular derangements that occur following SAH, including cerebral vasospasm, myocardial stunning, acute lung injury, cerebral salt wasting, perturbed glucose metabolism and alterations in thermal regulation.[6], [7], [10] Treatment strategies that target these complications in isolation, such as those used in recent trials for the treatment and prevention of vasospasm, have failed to yield improvements in morbidity and mortality,[11], [12], [13] perhaps because they fail to address inflammation as the putative underlying etiology.
Poor admission clinical grade (Hunt–Hess) is one of the most important determinants of outcome after aSAH.14 We hypothesized that poor admission clinical grade may reflect the extent of ultra-early brain injury and the cerebral inflammatory response initiated at the time of aneurysm rupture. Therefore, we sought to identify factors known to contribute to cerebral inflammation, and markers of early cerebral dysfunction, in one of the largest clinical series of patients with aSAH presented to date, in an effort to test the hypothesis that early brain injury and inflammation are associated with poor admission clinical grade in this patient population.
Section snippets
Patient population
As part of the Columbia University Subarachnoid Hemorrhage Outcomes Project, 850 consecutive patients with SAH admitted to the Neurological Intensive Care Unit of Columbia University Medical Center between 15 September 1997 and 14 July 2008 were prospectively enrolled.[15], [16] The study was approved by the Columbia University Institutional Review Board. The diagnosis of SAH was established on the basis of computed tomography (CT) scans obtained at admission or xanthochromia of the
Results
Between 15 September 1997 and 14 July 2008, 850 patients were admitted to the Neurological Intensive Care Unit of Columbia University Medical Center with a diagnosis of aSAH. The median age of these patients was 54 years, with a 25th percentile of 44 years and a 75th percentile of 64 years. Fifty-one percent were Caucasian, and 67% were female. Twenty-five percent of these patients (n = 213) were admitted with Hunt–Hess grade 4–5 (Table 1).
Patients with a poor admission clinical grade (poor-grade
Discussion
Despite recent advances in the treatment of patients after SAH, morbidity and mortality rates have failed to improve significantly.7 Vasospasm is one of the most significant causes of morbidity and mortality after SAH, yet recent trials aimed at improving cerebral blood flow or mitigating vasospasm following aSAH have had limited success in improving overall outcome.[11], [12], [13] These failures may be explained in part by a perspective that incorporates cerebral vasospasm as but one sequela
References (28)
- et al.
Multimodality monitoring in neurocritical care
Crit Care Med
(2007) - et al.
New insights into the causes and therapy of cerebral vasospasm following subarachnoid hemorrhage
Drug Discov Today
(2008) - et al.
Cerebral vasospasm following aneurysmal subarachnoid hemorrhage
Stroke
(1985) - et al.
The risk of subarachnoid and intracerebral hemorrhages in blacks as compared with whites
N Engl J Med
(1992) - et al.
Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage
Stroke
(1994) - et al.
p53 may play an orchestrating role in apoptotic cell death after experimental subarachnoid hemorrhage
Neurosurgery
(2007) - et al.
Vasospasm and p53-induced apoptosis in an experimental model of subarachnoid hemorrhage
Stroke
(2006) - et al.
Mechanisms of early brain injury after subarachnoid hemorrhage
J Cereb Blood Flow Metab
(2006) - et al.
Subarachnoid hemorrhage: is it time for a new direction?
Stroke
(2009) - et al.
Limited role of inducible nitric oxide synthase in blood-brain barrier function after experimental subarachnoid hemorrhage
J Neurotrauma
(2006)
Inhibition of c-Jun N-terminal kinase pathway attenuates cerebral vasospasm after experimental subarachnoid hemorrhage through the suppression of apoptosis
Acta Neurochir Suppl
Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation
Neurosurgery
Calcium antagonists for aneurysmal subarachnoid haemorrhage
Cochrane Database Syst Rev
Calcium antagonists for aneurysmal subarachnoid hemorrhage
Stroke
Cited by (30)
Temperature management in acute brain injury: A systematic review of clinical evidence
2020, Clinical Neurology and NeurosurgeryThe diagnostic value of complete blood count parameters in patients with subarachnoid hemorrhage
2017, Turkish Journal of Emergency MedicineThe prognostic value of plasma thrombospondin-1 concentrations after aneurysmal subarachnoid hemorrhage
2015, Clinica Chimica ActaCitation Excerpt :Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of cerebrovascular accident that carries high morbidity and mortality rates [1,2]. The World Federation of Neurological Surgeons (WFNS) grade and Fisher grade are known to be associated highly with poor outcomes after aSAH [3–5]. However, a readily measurable marker predicting poor outcomes early may help in early intervention and may improve the outcome after aSAH.
The prognostic value of plasma soluble CD40 ligand levels following aneurysmal subarachnoid hemorrhage
2015, Thrombosis ResearchCitation Excerpt :Pathological findings has revealed that inflammatory cells were detectable in brain tissues after SAH and peripheral blood and cerebrospinal fluid concentrations of several proinflammatory cytokines such as interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha, are elevated and related to the clinical severity of aSAH. Accumulating evidence has demonstrated the crucial role of inflammatory process in the pathophysiological mechanism of aSAH [3,4]. The role of sCD40L in aSAH remains unclear but it is possible that its proinflamatory effects [13,40] could contribute to the pathophysiology of aSAH.
Autonomic dysfunction syndromes after acute brain injury
2015, Handbook of Clinical NeurologyCitation Excerpt :Other data demonstrate worsened functional outcomes for patients with treatment-refractory fever within the first 10 days following SAH, with increased mortality, severe functional disability, and more severe cognitive impairment. Even in the lowest grade, mildest SAH patients, a single fever during the first 10 days postinjury is associated with overall worsened patient outcomes (Hanafy et al., 2010). At present, available data do not clearly show that aggressive temperature control results in improved outcomes (Broessner et al., 2010).