Thick and diffuse cisternal clot independently predicts vasospasm-related morbidity and poor outcome after aneurysmal subarachnoid hemorrhage

Abstract

<jats:sec><jats:title>OBJECTIVE</jats:title><jats:p>Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant morbidity and mortality. The presence of thick, diffuse subarachnoid blood may portend a worse clinical course and outcome, independently of other known prognostic factors such as age, aneurysm size, and initial clinical grade.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>In this post hoc analysis, patients with aSAH undergoing surgical clipping (n = 383) or endovascular coiling (n = 189) were pooled from the placebo arms of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS)–2 and CONSCIOUS-3 randomized, double-blind, placebo-controlled phase 3 studies, respectively. Patients without and with thick, diffuse SAH (≥ 4 mm thick and involving ≥ 3 basal cisterns) on admission CT scans were compared. Clot size was centrally adjudicated. All-cause mortality and vasospasm-related morbidity at 6 weeks and Glasgow Outcome Scale–Extended (GOSE) scores at 12 weeks after aSAH were assessed. The effect of the thick and diffuse cisternal aSAH on vasospasm-related morbidity and mortality, and on poor clinical outcome at 12 weeks, was evaluated using logistic regression models.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>Overall, 294 patients (51.4%) had thick and diffuse aSAH. Compared to patients with less hemorrhage burden, these patients were older (median age 55 vs 50 years) and more often had World Federation of Neurosurgical Societies (WFNS) grade III–V SAH at admission (24.1% vs 16.5%). At 6 weeks, all-cause mortality and vasospasm-related morbidity occurred in 36.1% (95% CI 30.6%–41.8%) of patients with thick, diffuse SAH and in 14.7% (95% CI 10.8%–19.5%) of those without thick, diffuse SAH. Individual event rates were 7.5% versus 2.5% for all-cause death, 19.4% versus 6.8% for new cerebral infarct, 28.2% versus 9.4% for delayed ischemic neurological deficit, and 24.8% versus 10.8% for rescue therapy due to cerebral vasospasm, respectively. Poor clinical outcome (GOSE score ≥ 4) was observed in 32.7% (95% CI 27.3%–38.3%) and 16.2% (95% CI 12.1%–21.1%) of patients with and without thick, diffuse SAH, respectively.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>In a large, centrally adjudicated population of patients with aSAH, WFNS grade at admission and thick, diffuse SAH independently predicted vasospasm-related morbidity and poor 12-week clinical outcome. Patients with thick, diffuse cisternal SAH may be an important cohort to target in future clinical trials of treatment for vasospasm.</jats:p></jats:sec>

A Quantitative Subarachnoid Hemorrhage Grading System, Including Supratentorial and Infratentorial Cisterns, With Multiplanar Computed Tomography Reformations

“…Some studies have categorized SAH with a thickness of >4 mm as "thick SAH clots." Observation of "thick SAH clots" in three or more cisterns was used to distinguish diffuse SAH and successfully predict the risk of vasospasm-induced morbidity and outcomes [2,18]. Unlike the majority of qualitative SAH scales, the design of our scale is well suited to the additional measurement of the short-axis thicknesses of SAH and clots in as many cisterns as desired, with multiplanar CT reformations [5][6][7]9].…”

Inhibition of caspase-1-mediated inflammasome activation reduced blood coagulation in cerebrospinal fluid after subarachnoid haemorrhage

“…1 Evidence suggests that the thick and diffuse blood distribution in cerebrospinal fluid (CSF) is the main risk factor of severe clinical course and poor outcome in SAH patients. 2,3 Blood components with secondary products (such as coagulation and degradation products) trigger a series of pathophysiological changes in both the acute and chronic stages after SAH. 4 Surgical interventions, such as lumbar drainage (LD) and external ventricular drainage (EVD), are widely used in the current clinical setting to facilitate bloody CSF clearance in SAH patients.…”

“…The CSF circulation is severely disturbed in both acute and late phases after SAH, which directly leads to increased intracerebral pressure (ICP), decreased cerebral blood perfusion, brain oedema formation, and hydrocephalus. 7À10 The blood coagulation response to SAH in the subarachnoid space is considered the leading cause of CSF flow abnormalities, 2,3,8,9,11 which directly blocks the ventricular system and arachnoid granules with the resultant CSF retention and acute hydrocephalus. 12,13 The coagulation cascade leads to fibrin clotting and deposition in the subarachnoid space and perivascular space, which further blocks the CSFinterstitial fluid (ISF) exchange and induces cerebral vasospasm and the neuroinflammatory response.…”

Potential role of serum hypoxia-inducible factor 1alpha as a biomarker of delayed cerebral ischemia and poor clinical outcome after human aneurysmal subarachnoid hemorrhage: A prospective, longitudinal, multicenter, and observational study

“…Hunt–Hess scale and modified Fisher scale are often used to assess illness severity and predict clinical outcomes of aSAH ( 3 ). Extended Glasgow outcome scale (GOSE) is conventionally regarded as a prognostic parameter in some brain injury diseases, including aSAH ( 4 ). Delayed cerebral ischemia (DCI) is a usually observed adverse event after aSAH, which is associated with an increased risk of a poor outcome for patients with aSAH ( 5 ).…”