Safety and effectiveness of lumbar cerebrospinal fluid drainage to prevent delayed cerebral ischemia after fisher grade 3 subarachnoid hemorrhage with minimal intraventricular hemorrhage

BackgroundDelayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) has a multifactorial pathophysiology, with immune dysregulation being an important component. The neutrophil–lymphocyte ratio (NLR) is an established prognostic marker in patients with cancer, cardiac disease, and sepsis.ObjectiveTo determine whether there is a relationship between NLR and DCI in patients with aSAH.MethodsWe evaluated 1067 patients with aSAH between 2006 and 2015 enrolled in a single-center, prospective, observational cohort study. Admission white blood cell differentials (NLR) were analyzed using a cut-off point of ≥5.9. DCI from cerebral vasospasm was defined as the occurrence of focal neurological impairment, or a decrease in at least two points on the Glasgow Coma Scale, which was not apparent immediately after aneurysm occlusion, and could not be attributed to other causes. Cerebral infarct was defined as a new infarct on CT that was not visible on the admission or immediate postoperative scan, when the cause was thought to be vasospasm by the research team. Logistic regression models were generated.ResultsWe found that 768 (72%) patients had an admission NLR ≥5.9. In a multivariable model, elevated NLR was associated with poor admission Hunt-Hess grade (OR=1.6, 95% CI 1.2 to 2.6, p=0.005), Caucasian ethnicity (OR=2.6, 95% CI 1.9 to 3.7, p<0.001), anterior aneurysm location (OR=1.7, 95% CI 1.2 to 2.4, p=0.004), loss of consciousness at ictus (OR=1.4, 95% CI 1.0 to 2.0, p=0.055), and thick SAH (modified Fisher grade ≥3) (OR=1.8, 95% CI 1.3 to 2.4, p<0.001). Admission NLR predicted development of delayed cerebral ischemia (DCI) (OR=1.7; 95% CI 1.1 to 2.5, p=0.008) after controlling for known predictors such as age, poor admission clinical grade, thick SAH blood, and elevated admission mean arterial pressure.ConclusionsThis study provides further evidence of the association between inflammation and DCI. Admission NLR is a readily available and convenient biomarker that may be a clinically useful tool for prognostication when evaluating aSAH.

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Isolated Intraventricular Hemorrhage Associated with Cerebral Vasospasm and Delayed Cerebral Ischemia following Arteriovenous Malformation Rupture

Interventional Neurology ◽

10.1159/000490583 ◽

2018 ◽

Vol 7 (6) ◽

pp. 479-489 ◽

Cited By ~ 1

Author(s):

Krishna Amuluru ◽

Fawaz Al-Mufti ◽

Charles E. Romero ◽

Chirag D. Gandhi

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Arteriovenous Malformation ◽

Cerebral Angiography ◽

Intraventricular Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Statistical Significance ◽

Delayed Cerebral Ischemia ◽

Ruptured Avm ◽

Level Of Significance

Background: Although it is well characterized in aneurysmal subarachnoid hemorrhage, vasospasm is exceedingly rare following cerebral arteriovenous malformation (AVM) rupture. Subsequently, this complication is poorly characterized with regard to delayed cerebral ischemia (DCI). We review cases of ruptured AVM to assess the frequency and severity of vasospasm on cerebral angiography, and DCI. Summary: We reviewed our institutional database of acute intracranial hemorrhages between 2005 and 2014. We identified patients with cerebral AVM rupture and evidence of vasospasm, which was confirmed with digital subtraction angiography (DSA). Cerebral angiograms were evaluated by 2 blinded neurointerventionalists for vasospasm. Statistical analyses were conducted on the angiographic results and variables of interest to determine predictors and associations of vasospasm and DCI. Thirty-six patients with acute intracranial hemorrhage due to ruptured cerebral AVM subsequently underwent cerebral angiography. The interrater reliability for vasospasm was 0.81. The incidence of vasospasm was 13.9% and the incidence of subsequent DCI was 11.1%. A significant relationship existed between isolated intraventricular hemorrhage and vasospasm (p = 0.001) and subsequent DCI (p = 0.006). Radiographic vasospasm was associated with DCI in 80% of the patients (p < 0.0001). No statistical significance existed between subarachnoid hemorrhage and the development of vasospasm or DCI (p = 1.000 and p = 0.626, respectively). All differences were significant at a 99% level of significance. Key Message: In cases of ruptured AVM, isolated intraventricular hemorrhage appears to be an independent risk factor for vasospasm and DCI. Vasospasm must be considered during late neurological deterioration following AVM hemorrhage, especially in the setting of isolated intraventricular hemorrhage.

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Increased Mitochondrial Dysfunction Associated with Autophagy and Mitophagy in Cerebrospinal Fluid Cells Following Subarachnoid Hemorrhage in Patients with Delayed Cerebral Ischemia

10.21203/rs.3.rs-394833/v1 ◽

2021 ◽

Author(s):

Dong Hyuk Youn ◽

Youngmi Kim ◽

Bong Jun Kim ◽

Myeong Seon Jeong ◽

Jooeun Lee ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Mitochondrial Dysfunction ◽

Delayed Cerebral Ischemia ◽

Underlying Mechanism ◽

Autophagic Flux ◽

Immunogold Staining ◽

Csf Cells ◽

Insight Into

Abstract Decreased mitochondrial membrane potential in cerebrospinal fluid (CSF) was observed in patients with subarachnoid hemorrhage (SAH) accompanied with delayed cerebral ischemia (DCI); however, the underlying mechanism remains unclear. We evaluated the mitochondrial dysfunction associated with autophagy and mitophagy in CSF cells for possible insight into DCI pathogenesis. CSF samples were collected from 56 SAH patients (DCI, n=21; and non-DCI, n=35). We analyzed CSF cells using autophagy and mitophagy markers (DAPK1, BNIP3L, BAX, PINK1, ULK1, and NDP52) via qRT-PCR and western blotting of proteins (BECN1, LC3, and p62). Confocal microscopy and immunogold staining were performed to demonstrate the differentially expression of markers within dysfunctional mitochondria. Significant induction of autophagic flux with accumulation of autophagic vacuoles, increased expression of BECN1, LC3-II, and p62 degradation were observed during DCI. DCI patients showed a significantly increased mRNA expression (2-ΔCt) than non-DCI patients: DAPK1, 0.279 (0.220–0.297) in DCI vs. 0.043 (0.021–0.086) in non-DCI; BNIP3L, 0.134 (0.060–0.202) in DCI vs. 0.045 (0.020–0.101) in non-DCI; and PINK1, 0.064 (0.044–0.810) in DCI vs. 0.045 (0.012–0.063) in non-DCI. Other markers including BAX, ULK1, and NDP52 did not differ significantly. The vWF-positive CSF cells showed a colocalization with antibodies for DAPK1, BNIP3L/NIX, PINK1, and BECN1 with dysfunctional mitochondria. Increased dysfunctional mitochondria associated with autophagy and mitophagy are closely associated with DCI pathogenesis.

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Does intrathecal nicardipine for cerebral vasospasm following subarachnoid hemorrhage correlate with reduced delayed cerebral ischemia? A retrospective propensity score–based analysis

Journal of Neurosurgery ◽

10.3171/2020.12.jns203673 ◽

2021 ◽

pp. 1-10

Author(s):

Ofer Sadan ◽

Hannah Waddel ◽

Reneé Moore ◽

Chen Feng ◽

Yajun Mei ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Propensity Score ◽

Functional Outcome ◽

Cerebral Vasospasm ◽

Delayed Cerebral Ischemia ◽

University Hospital ◽

World Federation ◽

Ventriculoperitoneal Shunting ◽

Fisher Grade

OBJECTIVE Cerebral vasospasm and delayed cerebral ischemia (DCI) contribute to poor outcome following subarachnoid hemorrhage (SAH). With the paucity of effective treatments, the authors describe their experience with intrathecal (IT) nicardipine for this indication. METHODS Patients admitted to the Emory University Hospital neuroscience ICU between 2012 and 2017 with nontraumatic SAH, either aneurysmal or idiopathic, were included in the analysis. Using a propensity-score model, this patient cohort was compared to patients in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository who did not receive IT nicardipine. The primary outcome was DCI. Secondary outcomes were long-term functional outcome and adverse events. RESULTS The analysis included 1351 patients, 422 of whom were diagnosed with cerebral vasospasm and treated with IT nicardipine. When compared with patients with no vasospasm (n = 859), the treated group was significantly younger (mean age 51.1 ± 12.4 years vs 56.7 ± 14.1 years, p < 0.001), had a higher World Federation of Neurosurgical Societies score and modified Fisher grade, and were more likely to undergo clipping of the ruptured aneurysm as compared to endovascular treatment (30.3% vs 11.3%, p < 0.001). Treatment with IT nicardipine decreased the daily mean transcranial Doppler velocities in 77.3% of the treated patients. When compared to patients not receiving IT nicardipine, treatment was not associated with an increased rate of bacterial ventriculitis (3.1% vs 2.7%, p > 0.1), yet higher rates of ventriculoperitoneal shunting were noted (19.9% vs 8.8%, p < 0.01). In a propensity score comparison to the SAHIT database, the odds ratio (OR) to develop DCI with IT nicardipine treatment was 0.61 (95% confidence interval [CI] 0.44–0.84), and the OR to have a favorable functional outcome (modified Rankin Scale score ≤ 2) was 2.17 (95% CI 1.61–2.91). CONCLUSIONS IT nicardipine was associated with improved outcome and reduced DCI compared with propensity-matched controls. There was an increased need for permanent CSF diversion but no other safety issues. These data should be considered when selecting medications and treatments to study in future randomized controlled clinical trials for SAH.

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Cerebrospinal Fluid 20-HETE Is Associated With Delayed Cerebral Ischemia and Poor Outcomes After Aneurysmal Subarachnoid Hemorrhage

Stroke ◽

10.1161/strokeaha.110.605816 ◽

2011 ◽

Vol 42 (7) ◽

pp. 1872-1877 ◽

Cited By ~ 34

Author(s):

Elizabeth A. Crago ◽

Bhavani P. Thampatty ◽

Paula R. Sherwood ◽

Chie-Wen J. Kuo ◽

Catherine Bender ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Poor Outcomes

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Interleukin 6 in cerebrospinal fluid is a biomarker for delayed cerebral ischemia (DCI) related infarctions after aneurysmal subarachnoid hemorrhage

Scientific Reports ◽

10.1038/s41598-020-79586-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sami Ridwan ◽

Alexander Grote ◽

Matthias Simon

Keyword(s):

Cerebrospinal Fluid ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Interleukin 6 ◽

Time Course ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Interindividual Variations ◽

Potential Biomarker ◽

Diagnostic Usefulness

AbstractInterleukin 6 (IL-6) is a prominent proinflammatory cytokine and has been discussed as a potential biomarker for delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage. In the present study we have analyzed the time course of serum and cerebrospinal fluid (CSF) IL-6 levels in 82 patients with severe aneurysmal subarachnoid hemorrhage (SAH) requiring external ventricular drains in correlation to angiographic vasospasm, delayed cerebral ischemia, secondary infarctions and other clinical parameters. We observed much higher daily mean IL-6 levels (but also large interindividual variations) in the CSF than the serum of the patients with a peak between days 4 and 14 including a maximum on day 5 after SAH. Individual CSF peak levels correlated significantly with DCI (mean day 4–14 peak, DCI: 26,291 ± 24,159 pg/ml vs. no DCI: 16,184 ± 13,163 pg/ml; P = 0.023). Importantly, CSF IL-6 levels differed significantly between cases with DCI and infarctions and patients with DCI and no infarction (mean day 4–14 peak, DCI with infarction: 37,209 ± 26,951 pg/ml vs. DCI, no infarction: 15,123 ± 11,239 pg/ml; P = 0.003), while findings in the latter patient group were similar to cases with no vasospasm (mean day 4–14 peak, DCI, no infarction: 15,123 ± 11,239 vs. no DCI: 15,840 ± 12,979; P = 0.873). Together, these data support a potential role for elevated CSF IL-6 levels as a biomarker for DCI with infarction rather than for DCI in general. This fits well with a growing body of evidence linking neuroinflammation to ischemia and infarction, but (together with the large interindividual variations observed) limits the diagnostic usefulness of CSF IL-6 levels in SAH patients.

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Mitochondrial dysfunction associated with autophagy and mitophagy in cerebrospinal fluid cells of patients with delayed cerebral ischemia following subarachnoid hemorrhage

Scientific Reports ◽

10.1038/s41598-021-96092-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Dong Hyuk Youn ◽

Youngmi Kim ◽

Bong Jun Kim ◽

Myeong Seon Jeong ◽

Jooeun Lee ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Mitochondrial Dysfunction ◽

Delayed Cerebral Ischemia ◽

Multivariable Logistic Regression Analysis ◽

Autophagic Flux ◽

Immunogold Staining ◽

Csf Cells ◽

Insight Into

AbstractDecreased mitochondrial membrane potential in cerebrospinal fluid (CSF) was observed in patients with subarachnoid hemorrhage (SAH) accompanied by delayed cerebral ischemia (DCI). However, whether abnormal mechanisms of mitochondria are associated with the development of DCI has not been reported yet. Under cerebral ischemia, mitochondria can transfer into the extracellular space. Mitochondrial dysfunction can aggravate neurologic complications. The objective of this study was to evaluate whether mitochondrial dysfunction might be associated with autophagy and mitophagy in CSF cells to provide possible insight into DCI pathogenesis. CSF samples were collected from 56 SAH patients (DCI, n = 21; and non-DCI, n = 35). We analyzed CSF cells using autophagy and mitophagy markers (DAPK1, BNIP3L, BAX, PINK1, ULK1, and NDP52) via qRT-PCR and western blotting of proteins (BECN1, LC3, and p62). Confocal microscopy and immunogold staining were performed to demonstrate the differentially expression of markers within dysfunctional mitochondria. Significant induction of autophagic flux with accumulation of autophagic vacuoles, increased expression of BECN1, LC3-II, and p62 degradation were observed during DCI. Compared to non-DCI patients, DCI patients showed significantly increased mRNA expression levels (2−ΔCt) of DAPK1, BNIP3L, and PINK1, but not BAX, ULK1, or NDP52. Multivariable logistic regression analysis revealed that Hunt and Hess grade ≥ IV (p = 0.023), DAPK1 (p = 0.003), and BNIP3L (p = 0.039) were related to DCI. Increased mitochondrial dysfunction associated with autophagy and mitophagy could play an important role in DCI pathogenesis.

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