The Pathogenesis of Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage

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.

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Targeting High Mobility Group Box 1 in Subarachnoid Hemorrhage: A Systematic Review

International Journal of Molecular Sciences ◽

10.3390/ijms21082709 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2709 ◽

Cited By ~ 1

Author(s):

Sajjad Muhammad ◽

Shafqat Rasul Chaudhry ◽

Ulf Dietrich Kahlert ◽

Martin Lehecka ◽

Miikka Korja ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Brain Damage ◽

Molecular Mechanisms ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

High Mobility ◽

High Mobility Group ◽

Endovascular Coiling ◽

Pharmacological Interventions

Aneurysmal subarachnoid hemorrhage (aSAH) is a complex and potentially deadly disease. Neurosurgical clipping or endovascular coiling can successfully obliterate ruptured aneurysms in almost every case. However, despite successful interventions, the clinical outcomes of aSAH patients are often poor. The reasons for poor outcomes are numerous, including cerebral vasospasm (CVS), post-hemorrhagic hydrocephalus, systemic infections and delayed cerebral ischemia. Although CVS with subsequent cerebral ischemia is one of the main contributors to brain damage after aSAH, little is known about the underlying molecular mechanisms of brain damage. This review emphasizes the importance of pharmacological interventions targeting high mobility group box 1 (HMGB1)-mediated brain damage after subarachnoid hemorrhage (SAH) and CVS. We searched Pubmed, Ovid medline and Scopus for “subarachnoid hemorrhage” in combination with “HMGB1”. Based on these criteria, a total of 31 articles were retrieved. After excluding duplicates and selecting the relevant references from the retrieved articles, eight publications were selected for the review of the pharmacological interventions targeting HMGB1 in SAH. Damaged central nervous system cells release damage-associated molecular pattern molecules (DAMPs) that are important for initiating, driving and sustaining the inflammatory response following an aSAH. The discussed evidence suggested that HMGB1, an important DAMP, contributes to brain damage during early brain injury and also to the development of CVS during the late phase. Different pharmacological interventions employing natural compounds with HMGB1-antagonizing activity, antibody targeting of HMGB1 or scavenging HMGB1 by soluble receptors for advanced glycation end products (sRAGE), have been shown to dampen the inflammation mediated brain damage and protect against CVS. The experimental data suggest that HMGB1 inhibition is a promising strategy to reduce aSAH-related brain damage and CVS. Clinical studies are needed to validate these findings that may lead to the development of potential treatment options that are much needed in aSAH.

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

Stroke ◽

10.1161/str.52.suppl_1.p756 ◽

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.

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Aneurysmal Subarachnoid Hemorrhage and Vasospasm

AACN Advanced Critical Care ◽

10.4037/aacnacc2018491 ◽

2018 ◽

Vol 29 (2) ◽

pp. 163-174 ◽

Cited By ~ 4

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.

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

Journal of Neurosurgery ◽

10.3171/2019.9.jns191366 ◽

2021 ◽

Vol 134 (1) ◽

pp. 95-101 ◽

Cited By ~ 2

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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Endoscopic third ventriculostomy may decrease shunt-dependency in patients with post-hemorrhagic hydrocephalus following aneurysmal subarachnoid hemorrhage

Interdisciplinary Neurosurgery ◽

10.1016/j.inat.2021.101300 ◽

2021 ◽

pp. 101300

Author(s):

Luca H. Debs ◽

Scott Y. Rahimi ◽

Martin J. Rutkowski ◽

Samuel D. Macomson

Keyword(s):

Subarachnoid Hemorrhage ◽

Endoscopic Third Ventriculostomy ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Third Ventriculostomy ◽

Shunt Dependency

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Prognostic Nomogram of Predictors for Shunt-Dependent Hydrocephalus in Patients with Aneurysmal Subarachnoid Hemorrhage Receiving External Ventricular Drain Insertion: A Single-Center Experience and Narrative Review

World Neurosurgery ◽

10.1016/j.wneu.2021.01.138 ◽

2021 ◽

Author(s):

Yao-Chung Yang ◽

Chun-Hao Yin ◽

Kuan-Ting Chen ◽

Pei-Chin Lin ◽

Ching-Chih Lee ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

External Ventricular Drain ◽

Narrative Review ◽

Single Center ◽

Single Center Experience

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Abstract 1122‐000094: EVD Weaning Criteria Decreases VPS/ETV Placement and Hospital Stay in Subarachnoid Hemorrhage Patients

Stroke: Vascular and Interventional Neurology ◽

10.1161/svin.01.suppl_1.000094 ◽

2021 ◽

Vol 1 (S1) ◽

Author(s):

Sachin A Kothari ◽

Mevish S Siddiq ◽

Scott Rahimi ◽

Manan Shah ◽

Klepper A Garcia

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Vasospasm ◽

Neurocritical Care ◽

External Ventricular Drain ◽

Third Ventriculostomy ◽

Chi Square ◽

Normal Limits ◽

Chi Square Analysis ◽

Weaning Criteria

Introduction : The Neurocritical Care Society encourages an external ventricular drain (EVD) wean “as quickly as is clinically feasible” but guidelines on achieving it are limited (1). This study aims to improve quality of care by sharing a protocol to initiate EVD weaning. These criteria were developed over 7 years and showed a reduction in ventriculoperitoneal shunt/endoscopic third ventriculostomy (VPS/ETV) placement and length of stay (LOS) at our institute compared to national averages. Methods : 151 subarachnoid hemorrhage (SAH) patients from January 2016 to January 2019 were analyzed. 60 aneurysmal SAH (aSAH) and 18 non‐aneurysmal nontraumatic SAH (naSAH) patients required EVD placement. A gradual EVD weaning protocol was initiated if patients met the following criteria: the reason for EVD placement has resolved or is resolving, quantity of CSF output must be <250mL over 24 hours, quality of CSF must be nonbloody, ICP must be within normal limits, and the patient must be neurologically stable. It was acceptable to wean when the patient had mild cerebral vasospasm, but not moderate to severe cerebral vasospasm. EVD weaning was performed by increasing drain height by 5 millimeters of mercury every 24 hours if criteria were met. Charts were reviewed for LOS and rate of VPS/ETV. Gender, age, race, wean failure incidence, infection rates, and SIADH/CSW rates were obtained. Results : Average LOS for aSAH patients with EVD at our institute was 20.35 days. Incidence of VPS/ETV was 11%. Chi‐square analysis was performed, and aSAH patients were found to have higher rates of VPS/ETV placement (p<0.001) and EVD wean failures (p<0.001) than naSAH patients. Conclusions : Our criteria to initiate EVD weaning provided a reduction in VPS/ETV placement among aSAH patients compared to national averages and provides a standardized approach to EVD management. aSAH patients at our institute had a lower incidence of VPS/ETV placement of 11% compared to 21% nationally (2). aSAH patients at our institute also had a lower LOS at 20.35 days compared to 21.5 days nationally (3).

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Bilateral subdural hygromas after endovascular coiling for ruptured aneurysmal subarachnoid hemorrhage: an unusual and rare complication

Oxford Medical Case Reports ◽

10.1093/omcr/omab062 ◽

2021 ◽

Vol 2021 (8) ◽

Author(s):

Walid O Ahmed ◽

Shady N Mashhour ◽

Marwa E Abdelfattah

Keyword(s):

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Rare Complication ◽

Mass Effect ◽

Contralateral Side ◽

Endovascular Coiling ◽

Neurological Assessment ◽

Ruptured Intracranial Aneurysm ◽

Significant Mass Effect

ABSTRACT Subarachnoid hemorrhage (SAH) with subdural hygroma (SH) was rarely reported after endovascular coiling. A 60-year-old male presented with impaired consciousness and convulsions due to SAH from a ruptured aneurysm. It was managed by endovascular coiling 20 h after the onset of symptoms. Serial brain imaging for 2 weeks revealed progressive bilateral SHs, more on contralateral side of leaking aneurysm. Management of SH was discussed in a multidisciplinary setting to be conservative as there was neither significant mass effect nor hydrocephalus. The patient recovered neurologically except for mild dysarthria. The SH persisted for 2 months and then cleared gradually. We concluded that SH may arise and become symptomatic as an unusual sequela of post-coiling of a ruptured intracranial aneurysm, in which the SH can complicate the clinical course of SAH. However, the symptomatic SH may resolve spontaneously and completely without any intervention, but needs meticulous neurological assessment and follow-up.

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