Thromboembolism and Delayed Cerebral Ischemia after Subarachnoid Hemorrhage: An Autopsy Study

Abstract OBJECTIVE: Recent findings have cast doubt on vasospasm as the sole cause of delayed cerebral ischemia after subarachnoid hemorrhage. METHODS: We reviewed the medical records of 29 patients who died after subarachnoid hemorrhage. Brain sections were taken from the insula, cingulate gyrus, and hippocampus. Adjacent sections were stained with hematoxylin-eosin and immunostained for thromboemboli. The density (burden) of the latter was calculated blindly and correlated with evidence for ischemia and with the amount of subarachnoid blood. RESULTS: There is a strong correlation between microclot burden and delayed cerebral ischemia. Patients with clinical or radiological evidence of delayed ischemia had mean microclot burdens of 10.0/cm2 (standard deviation [SD], ±6.6); those without had mean burdens of 2.8 (SD, ±2.6), a highly significant difference (P = 0.002). There is also significant association (P = 0.001) between microclot burden and histological evidence of ischemia, with the mean burdens being 10.9 in sections exhibiting severe ischemia and 4.1 in those in which ischemia was absent. Microclot burden is high in patients who died within 2 days of hemorrhage, decreasing on Days 3 and 4. In delayed ischemia, the numbers rise again late in the first week and remain high until after the second week. In contrast, the average clot burden is low in patients dying without developing delayed ischemia. The amount of blood on an individual slide influenced the microclot burden on that slide to a highly significant extent (P < 0.001). CONCLUSION: Thromboembolism after subarachnoid hemorrhage may contribute to delayed cerebral ischemia, which parallels that caused by vasospasm. The pathogenesis of thromboembolism is discussed.

Download Full-text

Cerebrospinal fluid macrophage migration inhibitory factor: a potential predictor of cerebral vasospasm and clinical outcome after aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/2019.6.jns19613 ◽

2020 ◽

Vol 133 (6) ◽

pp. 1786-1791 ◽

Cited By ~ 1

Author(s):

Kevin Kwan ◽

Orseola Arapi ◽

Katherine E. Wagner ◽

Julia Schneider ◽

Heustein L. Sy ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Cerebral Vasospasm ◽

Migration Inhibitory Factor ◽

Macrophage Migration Inhibitory Factor ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Inhibitory Factor ◽

Macrophage Migration ◽

Significant Difference

OBJECTIVEIn patients with aneurysmal subarachnoid hemorrhage (aSAH), poor outcomes have been shown to be correlated with subsequent cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). The identification of novel biomarkers may aid in the prediction of which patients are vulnerable to developing vasospasm, cerebral ischemia, and neurological deterioration.METHODSIn this prospective clinical study at North Shore University Hospital, patients with aSAH or normal pressure hydrocephalus (NPH) with external ventricular drains were enrolled. The concentration of macrophage migration inhibitory factor (MIF) in CSF was assessed for correlation with CV or DCI, the primary outcome measures.RESULTSTwenty-five patients were enrolled in the aSAH group and 9 were enrolled in the NPH group. There was a significant increase in aggregate CSF MIF concentration in patients with aSAH versus those with NPH (24.4 ± 19.2 vs 2.3 ± 1.1 ng/ml, p < 0.0002). Incidence of the day of peak MIF concentration significantly correlated with the onset of clinical vasospasm (rho = 0.778, p < 0.0010). MIF concentrations were significantly elevated in patients with versus those without evidence of DCI (18.7 ± 4.93 vs 8.86 ± 1.28 ng/ml, respectively, p < 0.0025). There was a significant difference in MIF concentrations between patients with infection versus those without infection (16.43 ± 4.21 vs 8.5 ± 1.22 ng/ml, respectively, p < 0.0119).CONCLUSIONSPreliminary evidence from this study suggests that CSF concentrations of MIF are correlated with CV and DCI. These results, however, could be confounded in the presence of clinical infection. A study with a larger patient sample size is necessary to corroborate these findings.

Download Full-text

Dynamic Change in Mean Platelet Volume and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Frontiers in Neurology ◽

10.3389/fneur.2020.571735 ◽

2020 ◽

Vol 11 ◽

Author(s):

Liuwei Chen ◽

Quanbin Zhang

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Mean Platelet Volume ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Dynamic Change ◽

Delayed Cerebral Ischemia ◽

Area Under The Curve ◽

Platelet Volume ◽

The Mean ◽

Change In Mean

Background: The mean platelet volume (MPV) has been shown to predict short-term outcomes in patients who have experienced aneurysmal subarachnoid hemorrhage (aSAH). The purpose of this study was to explore the temporal variation of MPV in patients with aSAH and its relationship to the development of delayed cerebral ischemia (DCI).Methods: Data from 197 consecutive aSAH patients who were treated at our institution between January 2017 and December 2019 were collected and analyzed. Blood samples to assess MPV were obtained at 1–3, 3–5, 5–7, and 7–9 d after the initial hemorrhage. Univariate and multivariate analyses were performed to investigate whether MPV was an independent predictor of DCI and the receiver operating characteristic (ROC) curve and area under the curve (AUC) were determined.Results: The MPV values in patients with DCI were significantly higher compared to those without DCI at 1–3, 3–5, 5–7, and 7–9 d after hemorrhage (P < 0.001). The trend for MPV in patients with DCI was increased at first and then decreased. The transition from increases to decreases occurred at 3–5 d after hemorrhage. The optimal cutoff value for MPV to accurately predict DCI was 10.35 fL at 3–5 d after aSAH in our cohort. Furthermore, the MPV observed at 3–5 d was an independent risk factor for DCI [odds ratio (OR) = 4.508, 95% confidence interval (CI): 2.665–7.626, P < 0.001].Conclusions: MPV is a dynamic variable that occurs during aSAH, and a high MPV at 3–5 days after hemorrhage is associated with the development of DCI.

Download Full-text

Invasive neuromonitoring with an extended definition of delayed cerebral ischemia is associated with improved outcome after poor-grade subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/2020.3.jns20375 ◽

2020 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Michael Veldeman ◽

Walid Albanna ◽

Miriam Weiss ◽

Catharina Conzen ◽

Tobias Philip Schmidt ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Care Center ◽

Cohort Analysis ◽

Tertiary Care ◽

Delayed Cerebral Ischemia ◽

Cerebral Microdialysis ◽

Poor Grade ◽

Significant Difference ◽

Definition Of

OBJECTIVEThe current definition of delayed cerebral ischemia (DCI) is based on clinical characteristics precluding its use in patients with poor-grade subarachnoid hemorrhage (SAH). Additional concepts to evaluate the unconscious patient are required. Invasive neuromonitoring (INM) may allow timely detection of metabolic and oxygenation crises before irreversible damage has occurred.METHODSThe authors present a cohort analysis of all consecutive SAH patients referred to a single tertiary care center between 2010 and 2018. The cohort (n = 190) was split into two groups: one before (n = 96) and one after (n = 94) the introduction of INM in 2014. A total of 55 poor-grade SAH patients were prospectively monitored using parenchymal oxygen saturation measurement and cerebral microdialysis. The primary outcome was the Glasgow Outcome Scale–Extended (GOSE) score after 12 months.RESULTSWith neuromonitoring, the first DCI event was detected earlier (mean 2.2 days, p = 0.002). The overall rate of DCI-related infarctions decreased significantly (from 44.8% to 22.3%; p = 0.001) after the introduction of invasive monitoring. After 12 months, a higher rate of favorable outcome was observed in the post-INM group, compared to the pre-INM group (53.8% vs 39.8%), with a significant difference in the GOSE score distribution (OR 4.86, 95% CI −1.17 to −0.07, p = 0.028).CONCLUSIONSIn this cohort analysis of poor-grade SAH patients, the introduction of INM and the extension of the classic DCI definition toward a functional dimension resulted in an earlier detection and treatment of DCI events. This led to an overall decrease in DCI-related infarctions and an improvement in outcome.

Download Full-text

Early Aneurysm Surgery and Prophylactic Hypervolemic Hypertensive Therapy for the Treatment of Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽

10.1227/00006123-198812000-00002 ◽

1988 ◽

Vol 23 (6) ◽

pp. 699-704 ◽

Cited By ~ 143

Author(s):

Robert A. Solomon ◽

Matthew E. Fink ◽

Laura Lennihan

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Volume Expansion ◽

Delayed Cerebral Ischemia ◽

Recent Experience ◽

Full Time ◽

Aneurysm Surgery ◽

Early Aneurysm Surgery ◽

Significant Difference ◽

Hypertensive Therapy

Abstract The prevailing sentiment of North American neurosurgeons is that there is no significant difference in overall morbidity between patients who are treated with early aneurysm surgery and those who are treated with delayed aneurysm surgery. This concept is based primarily on the high incidence of ischemic events after early intervention. Recent experience, however, indicates that prophylactic hypervolemic hypertensive therapy may be beneficial in reducing delayed ischemia after early aneurysm surgery. During the preceding 21 months, we have performed 125 operations for intracranial aneurysms. Fifty-six patients in this group presented less than 7 days after subarachnoid hemorrhage (SAH) (47 within 3 days) and were treated by a prospective protocol of urgent aneurysm surgery performed within 24 hours after presentation. In all cases, the aneurysm was clipped with the use of mannitol and spinal drainage for brain relaxation. All patients were then treated with prophylactic volume expansion therapy and induced hypertension with a central venous pressure or a Swan-Ganz catheter until the 14th day after SAH. Preoperatively, 17 patients were Hunt and Hess Grade I, 9 were Grade II, 28 were Grade III, and 2 were Grade IV. In this group of 56 patients at risk for delayed ischemia from vasospasm, 5 patients had significant intraoperative complications. Ten patients (18%) had delayed cerebral ischemia, totally reversible in 6 cases, with small infarcts in 3 cases, and with 1 death (2% mortality from delayed ischemia), there were 5 cases of shunted hydrocephalus, and 3 deaths from other complications. Overall, 41 patients (73%) returned to their premorbid occupations without neurological deficit. Four patients (7%) are independent with no neurological deficits, but have not returned to full-time employment. Four patients (7%) are independent, but have permanent deficits. Three patients (5%) are dependent on others for care, and 4 patients (7%) died. These data imply that delayed cerebral ischemia after SAH can be effectively minimized with prophylactic volume expansion therapy. Similar results have been reported for patients treated with calcium channel blocking agents. Given these techniques, perhaps the assumption that early operative intervention holds no advantage over delayed surgical treatment of an aneurysm rupture should be readdressed in a scientifically controlled fashion.

Download Full-text

Blood free Radicals Concentration Determined by Electron Paramagnetic Resonance Spectroscopy and Delayed Cerebral Ischemia Occurrence in Patients with Aneurysmal Subarachnoid Hemorrhage

Cell Biochemistry and Biophysics ◽

10.1007/s12013-017-0820-7 ◽

2017 ◽

Vol 75 (3-4) ◽

pp. 351-358 ◽

Cited By ~ 2

Author(s):

Grzywna Ewelina ◽

Stachura Krzysztof ◽

Moskala Marek ◽

Kruczala Krzysztof

Keyword(s):

Electron Paramagnetic Resonance ◽

Free Radicals ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Paramagnetic Resonance ◽

Significant Difference ◽

Electron Paramagnetic

Abstract Pathophysiology of delayed cerebral ischemia and cerebral vasospasm following aneurysmal subarachnoid hemorrhage is still poorly recognized, however free radicals are postulated as one of the crucial players. This study was designed to scrutinize whether the concentration of free radicals in the peripheral venous blood is related to the occurrence of delayed cerebral ischemia associated with cerebral vasospasm. Twenty-four aneurysmal subarachnoid hemorrhage patients and seven patients with unruptured intracranial aneurysm (control group) have been studied. Free radicals in patients’ blood have been detected by the electron paramagnetic resonance (CMH.HCl spin probe, 150 K, ELEXSYS E500 spectrometer) on admission and at least 72 h from disease onset. Delayed cerebral ischemia monitoring was performed by daily neurological follow-up and transcranial color coded Doppler. Delayed cerebral ischemia observed in six aneurysmal subarachnoid hemorrhage patients was accompanied by cerebral vasospasm in all six cases. No statistically significant difference in average free radicals concentration between controls and study subgroups was noticed on admission (p = .3; Kruskal–Wallis test). After 72 h free radicals concentration in delayed cerebral ischemia patients (3.19 ± 1.52 mmol/l) differed significantly from the concentration in aneurysmal subarachnoid hemorrhage patients without delayed cerebral ischemia (0.65 ± 0.37 mmol/l) (p = .012; Mann–Whitney test). These findings are consistent with our assumptions and seem to confirm the role of free radicals in delayed cerebral ischemia development. Preliminary results presented above are promising and we need perform further investigation to establish whether blood free radicals concentration may serve as the biomarker of delayed cerebral ischemia associated with cerebral vasospasm.

Download Full-text

Low intracranial pressure variability is associated with delayed cerebral ischemia and unfavorable outcome in aneurysmal subarachnoid hemorrhage

Journal of Clinical Monitoring and Computing ◽

10.1007/s10877-021-00688-y ◽

2021 ◽

Author(s):

Teodor Svedung Wettervik ◽

Timothy Howells ◽

Anders Hånell ◽

Elisabeth Ronne-Engström ◽

Anders Lewén ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Intracranial Pressure ◽

Early Phase ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Unfavorable Outcome ◽

Favorable Outcome ◽

Cerebral Vessel ◽

The Mean

Abstract Purpose High intracranial pressure variability (ICPV) is associated with favorable outcome in traumatic brain injury, by mechanisms likely involving better cerebral blood flow regulation. However, less is known about ICPV in aneurysmal subarachnoid hemorrhage (aSAH). In this study, we investigated the explanatory variables for ICPV in aSAH and its association with delayed cerebral ischemia (DCI) and clinical outcome. Methods In this retrospective study, 242 aSAH patients, treated at the neurointensive care, Uppsala, Sweden, 2008–2018, with ICP monitoring the first ten days post-ictus were included. ICPV was evaluated on three time scales: (1) ICPV-1 m—ICP slow wave amplitude of wavelengths between 55 and 15 s, (2) ICPV-30 m—the deviation from the mean ICP averaged over 30 min, and (3) ICPV-4 h—the deviation from the mean ICP averaged over 4 h. The ICPV measures were analyzed in the early phase (day 1–3), in the early vasospasm phase (day 4–6.5), and the late vasospasm phase (day 6.5–10). Results High ICPV was associated with younger age, reduced intracranial pressure/volume reserve (high RAP), and high blood pressure variability in multiple linear regression analyses for all ICPV measures. DCI was associated with reduced ICPV in both vasospasm phases. High ICPV-1 m in the post-ictal early phase and the early vasospasm phase predicted favorable outcome in multiple logistic regressions, whereas ICPV-30 m and ICPV-4 h in the late vasospasm phase had a similar association. Conclusions Higher ICPV may reflect more optimal cerebral vessel activity, as reduced values are associated with an increased risk of DCI and unfavorable outcome after aSAH.

Download Full-text