Abstract P756: Bilirubin Oxidation and Cerebral Vasospasm in Subarachnoid Hemorrhage: A Feasibility Study

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Weston R Gordon ◽  
Shweta Goswami ◽  
Jane Yang ◽  
Bailey Yekzamen ◽  
Michael G Abraham ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Prospective Study ◽  
Cerebral Vasospasm ◽  
Biochemical Markers ◽  
Time Course ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
External Ventricular Drain ◽  
Endovascular Coiling ◽  
Bilirubin Metabolism ◽  
High Degree

Introduction: Cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage (aSAH) is associated with a high degree of morbidity and mortality. In an adequate oxidative environment, certain products of bilirubin metabolism have been hypothesized to be a cause of CV. To our knowledge no prospective CSF collection has been performed to establish a time course for their formation in the clinical context of CV. We aimed to design a pilot study assessing the feasibility of collecting and storing CSF for analysis of potential biochemical markers for CV, and to evaluate which variables can accurately and reliably be measured for a larger prospective study. Methods: Adult patients with aSAH and an external ventricular drain (EVD) were enrolled. Patients who had complications following treatment of aSAH or who developed any neurological deterioration unrelated to the aSAH were excluded. CSF was extracted from patients on the initial day of EVD placement and then daily for a total of 10 days and frozen until data analysis. Heme, Heme Oxygenase (HO-1) and Cu/Zn-Superoxide Dismutase (SOD) were measured using commercially available assay kits. Results: Patients 1, 2 and 3 had modified Fisher grades of 2, 3 and 4, respectively. Patients 1 and 3 underwent endovascular coiling and patient 2 had surgical clipping. There were no complications and no CV. Heme concentrations were 40.0 ± 8.5 μm, 55.6 ± 7.7 μm, and 64.7 ± 0.4 μm on day of bleed (day 0) for patients 1, 2, and 3, respectively, and decreased in patients 1 and 2 on day 1. SOD concentrations peaked on day 2 for patient 1 (140.2 ± 15.6 ng/mL), on day 0 for patient 2 (25.8 ± 14.9 ng/mL), and on day 1 for patient 3 (215.9 ± 24.4 ng/mL). HO-1 concentrations peaked for all three patients on day 2 (14.6 ± 0.4, 17.6 ± 12.0 and 23.6 ± 5.4 ng/mL, respectively). Conclusions: The study was successful in completing our objective of establishing a protocol for collection, storage, and measurement of three potential biochemical markers in CSF. A larger prospective study will be performed to establish the time course of bilirubin metabolism and oxidation in the CSF relative to the clinical condition of CV in patients after aSAH.

Aneurysmal Subarachnoid Hemorrhage and Vasospasm

2018 ◽  
Vol 29 (2) ◽  
pp. 163-174 ◽  
Author(s):  
Shannon K. Burns ◽  
Kacie J. Brewer ◽  
Courtney Jenkins ◽  
Sally Miller
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
External Ventricular Drain ◽  
Delayed Cerebral Ischemia ◽  
Endovascular Coiling ◽  
Ruptured Aneurysms ◽  
The Past ◽  
Endovascular Interventions ◽  
Poor Outcomes

Aneurysmal subarachnoid hemorrhage is potentially fatal and is associated with poor outcomes in many patients. Advances in neurosurgical and medical management of ruptured aneurysms have improved mortality rates in patients with aneurysmal subarachnoid hemorrhage. Surgical and endovascular interventions, such as external ventricular drain placement, aneurysm clipping, and endovascular coiling, have been developed over the past few decades. Patients with aneurysmal subarachnoid hemorrhage are also at risk for cerebral vasospasm and delayed cerebral ischemia. This article describes the diagnosis and treatment of aneurysmal subarachnoid hemorrhage, vasospasm, and cerebral ischemia. Concurrent medical considerations and ideas for future neuroinflammatory vasospasm research are also discussed.

scholarly journals Osteopontin in the Cerebrospinal Fluid of Patients with Severe Aneurysmal Subarachnoid Hemorrhage

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 695 ◽  
Author(s):  
Maria Giulia Abate ◽  
Lorenza Moretto ◽  
Ilaria Licari ◽  
Teresa Esposito ◽  
Lorenzo Capuano ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Time Course ◽  
Independent Predictor ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
External Ventricular Drain ◽  
Aneurysm Rupture ◽  
High Morbidity ◽  
Weak Correlation ◽  
Poor Outcome

Aneurysmal subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. In SAH patients, plasma osteopontin (OPN) has been shown to independently predict poor outcome. The aim of the study is to investigate, in a selected population with severe SAH, OPN time course in cerebrospinal fluid (CSF) and plasma during the first week after aneurism rupture, and OPN prognostic value. We included 44 patients with the following criteria: (1) age 18 and 80 years, (2) diagnosis of SAH from cerebral aneurysm rupture, (3) insertion of external ventricular drain. Plasma and CSF were sampled at day 1, 4, and 8. OPN levels, in CSF and plasma, displayed a weak correlation on day 1 and were higher, in CSF, in all time points. Only in poor prognosis patients, OPN levels in CSF significantly increased at day 4 and day 8. Plasma OPN at day 1 and 4 was predictor of poor outcome. In conclusion, plasma and CSF OPN displays a weak correlation, on day 1. The higher levels of OPN found in the CSF compared to plasma, suggest OPN production within the CNS after SAH. Furthermore, plasma OPN, at day 1 and 4, seems to be an independent predictor of poor outcome.

scholarly journals The Pathogenesis of Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage

2021 ◽  
Vol 22 (9) ◽  
pp. 5050
Author(s):  
Lu-Ting Kuo ◽  
Abel Po-Hao Huang
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
External Ventricular Drain ◽  
Endovascular Coiling ◽  
Third Ventriculostomy ◽  
Chronic Hydrocephalus ◽  
Cellular Mechanisms ◽  
Surgical Interventions

Hydrocephalus is a common complication of aneurysmal subarachnoid hemorrhage (aSAH) and reportedly contributes to poor neurological outcomes. In this review, we summarize the molecular and cellular mechanisms involved in the pathogenesis of hydrocephalus following aSAH and summarize its treatment strategies. Various mechanisms have been implicated for the development of chronic hydrocephalus following aSAH, including alterations in cerebral spinal fluid (CSF) dynamics, obstruction of the arachnoid granulations by blood products, and adhesions within the ventricular system. Regarding molecular mechanisms that cause chronic hydrocephalus following aSAH, we carried out an extensive review of animal studies and clinical trials about the transforming growth factor-β/SMAD signaling pathway, upregulation of tenascin-C, inflammation-dependent hypersecretion of CSF, systemic inflammatory response syndrome, and immune dysregulation. To identify the ideal treatment strategy, we discuss the predictive factors of shunt-dependent hydrocephalus between surgical clipping and endovascular coiling groups. The efficacy and safety of other surgical interventions including the endoscopic removal of an intraventricular hemorrhage, placement of an external ventricular drain, the use of intraventricular or cisternal fibrinolysis, and an endoscopic third ventriculostomy on shunt dependency following aSAH were also assessed. However, the optimal treatment is still controversial, and it necessitates further investigations. A better understanding of the pathogenesis of acute and chronic hydrocephalus following aSAH would facilitate the development of treatments and improve the outcome.

Nimodipine pharmacokinetics after intraventricular injection of sustained-release nimodipine for subarachnoid hemorrhage

2021 ◽  
Vol 134 (1) ◽  
pp. 95-101 ◽  
Author(s):  
R. Loch Macdonald ◽  
Daniel Hänggi ◽  
Poul Strange ◽  
Hans Jakob Steiger ◽  
J Mocco ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Sustained Release ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
External Ventricular Drain ◽  
Plasma Concentrations ◽  
Intraventricular Injection ◽  
World Federation ◽  
Maximum Plasma ◽  
Clinical Trial Registration ◽  
Sustained Release Formulation

OBJECTIVEThe objective of this study was to measure the concentration of nimodipine in CSF and plasma after intraventricular injection of a sustained-release formulation of nimodipine (EG-1962) in patients with aneurysmal subarachnoid hemorrhage (SAH).METHODSPatients with SAH repaired by clip placement or coil embolization were randomized to EG-1962 or oral nimodipine. Patients were classified as grade 2–4 on the World Federation of Neurosurgical Societies grading scale for SAH and had an external ventricular drain inserted as part of their standard of care. Cohorts of 12 patients received 100–1200 mg of EG-1962 as a single intraventricular injection (9 per cohort) or they remained on oral nimodipine (3 per cohort). Plasma and CSF were collected from each patient for measurement of nimodipine concentrations and calculation of maximum plasma and CSF concentration, area under the concentration-time curve from day 0 to 14, and steady-state concentration.RESULTSFifty-four patients in North America were randomized to EG-1962 and 18 to oral nimodipine. Plasma concentrations increased with escalating doses of EG-1962, remained stable for 14 to 21 days, and were detectable at day 30. Plasma concentrations in the oral nimodipine group were more variable than for EG-1962 and were approximately equal to those occurring at the EG-1962 800-mg dose. CSF concentrations of nimodipine in the EG-1962 groups were 2–3 orders of magnitude higher than in the oral nimodipine group, in which nimodipine was only detected at low concentrations in 10% (21/213) of samples. In the EG-1962 groups, CSF nimodipine concentrations were 1000 times higher than plasma concentrations.CONCLUSIONSPlasma concentrations of nimodipine similar to those achieved with oral nimodipine and lasting for 21 days could be achieved after a single intraventricular injection of EG-1962. The CSF concentrations from EG-1962, however, were at least 2 orders of magnitude higher than those with oral nimodipine. These results supported a phase 3 study that demonstrated a favorable safety profile for EG-1962 but yielded inconclusive efficacy results due to notable differences in clinical outcome based on baseline disease severity.Clinical trial registration no.: NCT01893190 (ClinicalTrials.gov).

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