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8 pages, 410 KiB

Open AccessArticle

Outcome of Patients with Multiple Intracranial Aneurysms after Subarachnoid Hemorrhage and Future Risk of Rupture of Unruptured Aneurysm

by Seppo Juvela

J. Clin. Med. 2021, 10(8), 1712; https://doi.org/10.3390/jcm10081712 - 15 Apr 2021

Cited by 5 | Viewed by 2452

Abstract

The purpose was to study the risk of rupture of unruptured intracranial aneurysms (UIAs) of patients with multiple intracranial aneurysms after subarachnoid hemorrhage (SAH), in a long-term follow-up study, from variables known at baseline. Future rupture risk was compared in relation to outcome [...] Read more.

The purpose was to study the risk of rupture of unruptured intracranial aneurysms (UIAs) of patients with multiple intracranial aneurysms after subarachnoid hemorrhage (SAH), in a long-term follow-up study, from variables known at baseline. Future rupture risk was compared in relation to outcome after SAH. The series consists of 131 patients with 166 UIAs and 2854 person-years of follow-up between diagnosis of UIA and its rupture, death or the last follow-up contact. These were diagnosed before 1979, when UIAs were not treated in our country. Those patients with a moderate or severe disability after SAH, according to the Glasgow Outcome Scale, had lower rupture rates of UIA than those with a good recovery or minimal disability (4/37 or 11%, annual UIA rupture rate of 0.5% (95% confidence interval (CI) 0.1–1.3%) during 769 follow-up years vs. 27/94 or 29%, 1.3% (95% CI 0.9–1.9%) during 2085 years). Those with a moderate or severe disability differed from others by their older age. Those with a moderate or severe disability tended to have a decreased cumulative rate of aneurysm rupture (log rank test, p = 0.066) and lower relative risk of UIA rupture (hazard ratio 0.39, 95% CI 0.14–1.11, p = 0.077). Multivariable hazard ratios showed at least similar results, suggesting that confounding factors did not have a significant effect on the results. The results of this study without treatment selection of UIAs suggest that patients with a moderate or severe disability after SAH have a relatively low risk of rupture of UIAs. Their lower treatment indication may also be supported by their known higher treatment risks. Full article

(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Care and Diagnosis)

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10 pages, 1585 KiB

Open AccessArticle

Decreased Superoxide Dismutase Concentrations (SOD) in Plasma and CSF and Increased Circulating Total Antioxidant Capacity (TAC) Are Associated with Unfavorable Neurological Outcome after Aneurysmal Subarachnoid Hemorrhage

by Harald Krenzlin, Dominik Wesp, Jan Schmitt, Christina Frenz, Elena Kurz, Julia Masomi-Bornwasser, Johannes Lotz, Florian Ringel, Thomas Kerz and Naureen Keric

J. Clin. Med. 2021, 10(6), 1188; https://doi.org/10.3390/jcm10061188 - 12 Mar 2021

Cited by 5 | Viewed by 2411

Abstract

Background: Subarachnoid hemorrhage (SAH) is a devastating disease with high morbidity and mortality. Hypoxia-induced changes and hemoglobin accumulation within the subarachnoid space are thought to lead to oxidative stress, early brain injury, and delayed vasospasm. This study aimed to evaluate the antioxidant status [...] Read more.

Background: Subarachnoid hemorrhage (SAH) is a devastating disease with high morbidity and mortality. Hypoxia-induced changes and hemoglobin accumulation within the subarachnoid space are thought to lead to oxidative stress, early brain injury, and delayed vasospasm. This study aimed to evaluate the antioxidant status and its impact on neurological outcome in patients with aneurysmal SAH. Methods: In this prospective observational study, 29 patients with aneurysmal SAH were included (mean age 54.7 ± 12.4). Blood and cerebrospinal fluid (CSF) samples were collected on days (d) 1, 3, and 7. In addition, 29 patients without intracranial hemorrhage served as controls. The antioxidant system was analyzed by glutathione peroxidase (GSH-Px; U/L) and total and free glutathione-sulfhydryl (GSH; mg/L) in the plasma. Superoxide dismutase (SOD, U/mL) and total antioxidant capacity (TAC, µmol/L) were measured in the serum and CSF. Clinical data were compiled on admission (Hunt and Hess grade, Fisher grade, and GCS). Neurological and cognitive outcome (modified Rankin scale (mRS), Glasgow Outcome Scale Extended (GOSE) and Montreal Cognitive Assessment (MoCA)) was assessed after 6 weeks (6 w) and 6 months (6 m). Results: Plasma levels of SOD increased from day 1 to 7 after SAH (d1: 1.22 ± 0.36 U/L; d3: 1.25 ± 0.33 U/L, p = 0.99; d7: 1.52 ± 0.4 U/L, p = 0.019) and were significantly higher compared to controls (1.11 ± 0.27 U/L) at day 7 (p < 0.001). Concordantly, CSF levels of SOD increased from day 1 to 7 after SAH (d1: 1.22 ± 0.41 U/L; d3: 1.77 ± 0.73 U/L, p = 0.10; d7: 2.37 ± 1.29 U/L, p < 0.0001) without becoming significantly different compared to controls (1.74 ± 0.8 U/L, p = 0.09). Mean plasma TAC at day 1 (d1: 77.87 ± 49.72 µmol/L) was not statistically different compared to controls (46.74 ± 32.42 µmol/L, p = 0.25). TAC remained unchanged from day 1 to 7 (d3: 92.64 ± 68.58 µmol/L, p = 0.86; d7: 74.07 ± 54.95 µmol/L, p = 0.8) in plasma. TAC in CSF steeply declined from day 1 to 7 in patients with SAH becoming significantly different from controls at days 3 and 7 (d3: 177.3 ± 108.7 µmol/L, p = 0.0046; d7: 85.35 ± 103.9 µmol/L, p < 0.0001). Decreased SOD levels in plasma and CSF are associated with a worse neurological outcome 6 weeks (mRS: CSF p = 0.0001; plasma p = 0.027/GOSE: CSF p = 0.001; plasma p = 0.001) and 6 months (mRS: CSF p = 0.001; plasma p = 0.09/GOSE: CSF p = 0.001; plasma p = 0.001) after SAH. Increased plasma TAC correlated with a worse neurological outcome 6 weeks (mRS: p = 0.001/GOSE p = 0.001) and 6 months (mRS p = 0.001/GOSE p = 0.001) after SAH. Conclusion: In our study, a reduction in the antioxidative enzyme SOD and elevated TAC were associated with a poorer neurological outcome reflected by mRS and GOSE at 6 weeks and 6 months after SAH. A lower initial SOD CSF concentration was associated with the late deterioration of cognitive ability. These findings support the mounting evidence of the role of oxidative stress in early brain injury formation and unfavorable outcome after SAH. Full article

(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Care and Diagnosis)

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14 pages, 7125 KiB

Open AccessArticle

International Practice Variability in Treatment of Aneurysmal Subarachnoid Hemorrhage

by Jordi de Winkel, Mathieu van der Jagt, Hester F. Lingsma, Bob Roozenbeek, Eusebia Calvillo, Sherry H-Y. Chou, Peter H. Dziedzic, Nima Etminan, Judy Huang, Nerissa U. Ko, Robert Loch MacDonald, Renee L. Martin, Niteesh R. Potu, Chethan P. Venkatasubba Rao, Mervyn D. I. Vergouwen and Jose I. Suarez

J. Clin. Med. 2021, 10(4), 762; https://doi.org/10.3390/jcm10040762 - 14 Feb 2021

Cited by 27 | Viewed by 3727

Abstract

Prior research suggests substantial between-center differences in functional outcome following aneurysmal subarachnoid hemorrhage (aSAH). One hypothesis is that these differences are due to practice variability. To characterize practice variability, we sent a survey to 230 centers, of which 145 (63%) responded. Survey respondents [...] Read more.

Prior research suggests substantial between-center differences in functional outcome following aneurysmal subarachnoid hemorrhage (aSAH). One hypothesis is that these differences are due to practice variability. To characterize practice variability, we sent a survey to 230 centers, of which 145 (63%) responded. Survey respondents indicated that an estimated 65% of ruptured aneurysms were treated endovascularly. Sixty-five percent of aneurysms were treated within 24 h of symptom onset, 18% within 24–48 h, and eight percent within 48–72 h. Centers in the United States (US) and Europe (EU) treat aneurysms more often endovascularly (72% and 70% vs. 51%, respectively, US vs. other p < 0.001, and EU vs. other p < 0.01) and more often within 24 h (77% and 64% vs. 46%, respectively, US vs. other p < 0.001, EU vs. other p < 0.01) compared to other centers. Most centers aim for euvolemia (96%) by administrating intravenous fluids to 0 (53%) or +500 mL/day (41%) net fluid balance. Induced hypertension is more often used in US centers (100%) than in EU (87%, p < 0.05) and other centers (81%, p < 0.05), and endovascular therapies for cerebral vasospasm are used more often in US centers than in other centers (91% and 60%, respectively, p < 0.05). We observed significant practice variability in aSAH treatment worldwide. Future comparative effectiveness research studies are needed to investigate how practice variation leads to differences in functional outcome. Full article

(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Care and Diagnosis)

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10 pages, 893 KiB

Open AccessArticle

Edema Resolution and Clinical Assessment in Poor-Grade Subarachnoid Hemorrhage: Useful Indicators to Predict Delayed Cerebral Infarctions?

by Ramon Torné, Jhon Hoyos, Laura Llull, Ana Rodríguez-Hernández, Guido Muñoz, Ricard Mellado-Artigas, Daniel Santana, Leire Pedrosa, Alberto Di Somma, Luis San Roman, Sergio Amaro and Joaquim Enseñat

J. Clin. Med. 2021, 10(2), 321; https://doi.org/10.3390/jcm10020321 - 17 Jan 2021

Cited by 7 | Viewed by 2534

Abstract

Background: The level of consciousness and cerebral edema are among the indicators that best define the intensity of early brain injury following aneurysmal subarachnoid hemorrhage (aSAH). Although these indicators are usually altered in patients with a poor neurological status, their usefulness for selecting [...] Read more.

Background: The level of consciousness and cerebral edema are among the indicators that best define the intensity of early brain injury following aneurysmal subarachnoid hemorrhage (aSAH). Although these indicators are usually altered in patients with a poor neurological status, their usefulness for selecting patients at risk of cerebral infarction (CI) is not well established. Furthermore, little is known about the evolution of these indicators during the first week of post-ictal events. Our study focused on describing the association of the longitudinal course of these predictors with CI occurrence in patients with severe aSAH. Methods: Out of 265 aSAH patients admitted consecutively to the same institution, 80 patients with initial poor neurological status (WFNS 4–5) were retrospectively identified. After excluding 25 patients with early mortality, a total of 47 patients who underwent early CT (<3 days) and late CT (<7 days) acquisitions were included in the study. Early cerebral edema and delayed cerebral edema were calculated using the SEBES score, and the level of consciousness was recorded daily during the first week using the Glasgow Coma Scale (GCS). Results: There was a significant improvement in the SEBES (Early-SEBES median (IQR) = 3 (2–4) versus Delayed-SEBES = 2 (1–3); p = 0.001) and in GCS scores (B = 0.32; 95% CI 0.15–0.49; p = 0.001) during the first week. When comparing the ROC curves of Delayed-SEBES vs Early-SEBES as predictors of CI, no significant differences were found (Early-SEBES Area Under the Curve: 0.65; Delayed-SEBES: 0.62; p = 0.17). Additionally, no differences were observed in the relationship between the improvement in the GCS across the first week and the occurrence of CI (p = 0.536). Conclusions: Edema and consciousness level improvement did not seem to be associated with the occurrence of CI in a surviving cohort of patients with severe aSAH. Our results suggest that intensive monitoring should not be reduced in patients with a poor neurological status regardless of an improvement in cerebral edema and level of consciousness during the first week after bleeding. Full article

(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Care and Diagnosis)

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13 pages, 1049 KiB

Open AccessArticle

Brain-Specific Biomarkers as Mortality Predictors after Aneurysmal Subarachnoid Haemorrhage

by Jaroslaw Kedziora, Malgorzata Burzynska, Waldemar Gozdzik, Andrzej Kübler, Agnieszka Uryga, Magdalena Kasprowicz and Barbara Adamik

J. Clin. Med. 2020, 9(12), 4117; https://doi.org/10.3390/jcm9124117 - 20 Dec 2020

Cited by 6 | Viewed by 2267

Abstract

Aneurysmal subarachnoid haemorrhage (aSAH) is a serious condition with a high mortality and high permanent disability rate for those who survive the initial haemorrhage. The purpose of this study was to investigate markers specific to the central nervous system as potential in-hospital mortality [...] Read more.

Aneurysmal subarachnoid haemorrhage (aSAH) is a serious condition with a high mortality and high permanent disability rate for those who survive the initial haemorrhage. The purpose of this study was to investigate markers specific to the central nervous system as potential in-hospital mortality predictors after aSAH. In patients with an external ventricular drain, enolase, S100B, and GFAP levels were measured in the blood and cerebrospinal fluid (CSF) on days 1, 2, and 3 after aSAH. Compared to survivors, non-survivors showed a significantly higher peak of S100B and enolase levels in the blood (S100B: 5.7 vs. 1.5 ng/mL, p = 0.031; enolase: 6.1 vs. 1.4 ng/mL, p = 0.011) and the CSF (S100B: 18.3 vs. 0.9 ng/mL, p = 0.042; enolase: 109.2 vs. 6.1 ng/mL, p = 0.015). Enolase showed the highest level of predictability at 1.8 ng/mL in the blood (AUC of 0.873) and 80.0 ng/mL in the CSF (AUC of 0.889). The predictive ability of S100B was also very good with a threshold of 5.7 ng/mL in the blood (AUC 0.825) and 4.5 ng/mL in the CSF (AUC 0.810). In conclusion, enolase and S100B, but not GFAP, might be suitable as biomarkers for the early prediction of in-hospital mortality after aSAH. Full article

(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Care and Diagnosis)

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10 pages, 579 KiB

Open AccessArticle

Scoring of Growth of Unruptured Intracranial Aneurysms

by Seppo Juvela

J. Clin. Med. 2020, 9(10), 3339; https://doi.org/10.3390/jcm9103339 - 18 Oct 2020

Cited by 10 | Viewed by 3310

Abstract

The purpose was to obtain a reliable scoring for growth of unruptured intracranial aneurysms (UIAs) in a long-term follow-up study from variables known at baseline and to compare it with the ELAPSS (Earlier subarachnoid hemorrhage, Location of the aneurysm, Age > 60 years, [...] Read more.

The purpose was to obtain a reliable scoring for growth of unruptured intracranial aneurysms (UIAs) in a long-term follow-up study from variables known at baseline and to compare it with the ELAPSS (Earlier subarachnoid hemorrhage, Location of the aneurysm, Age > 60 years, Population, Size of the aneurysm, and Shape of the aneurysm) score obtained from an individual-based meta-analysis. The series consists of 87 patients with 111 UIAs and 1669 person-years of follow-up between aneurysm size measurements (median follow-up time per patient 21.7, range 1.2 to 51.0 years). These were initially diagnosed between 1956 and 1978, when UIAs were not treated in our country. ELAPSS scores at baseline did not differ between those with and those without aneurysm growth. The area under the curve (AUC) for the receiver operating curve (ROC) of the ELAPSS score for predicting long-term growth was fail (0.474, 95% CI 0.345–0.603), and the optimal cut-off point was obtained at ≥7 vs. <7 points for sensitivity (0.829) and specificity (0.217). In the present series UIA growth was best predicted by female sex (4 points), smoking at baseline (3 points), and age <40 years (2 points). The AUC for the ROC of the new scoring was fair (0.662, 95% CI 0.546–0.779), which was significantly better than that of ELAPSS score (p < 0.05). The optimal cut-off point was obtained at ≥4 vs. <4 points for sensitivity (0.971) and specificity (0.304). A new simple scoring consisting of only female sex, cigarette smoking and age <40 years predicted growth of an intracranial aneurysm in long-term follow-up, significantly better than the ELAPSS score. Full article

(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Care and Diagnosis)

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8 pages, 873 KiB

Open AccessArticle

Monitoring of Delayed Cerebral Ischemia in Patients with Subarachnoid Hemorrhage via Near-Infrared Spectroscopy

by Jeong Jin Park, Chulho Kim and Jin Pyeong Jeon

J. Clin. Med. 2020, 9(5), 1595; https://doi.org/10.3390/jcm9051595 - 24 May 2020

Cited by 18 | Viewed by 3020

Abstract

We investigated the role of near infrared spectroscopy (NIRS) in identifying delayed cerebral ischemia (DCI) in patients with subarachnoid hemorrhage (SAH). We measured the cerebral regional oxygen saturation (rSO2) continuously for 14 days. The differences in rSO2 according to DCI were analyzed. We [...] Read more.

We investigated the role of near infrared spectroscopy (NIRS) in identifying delayed cerebral ischemia (DCI) in patients with subarachnoid hemorrhage (SAH). We measured the cerebral regional oxygen saturation (rSO2) continuously for 14 days. The differences in rSO2 according to DCI were analyzed. We also compared the diagnostic accuracy of NIRS and transcranial Doppler ultrasonography (TCD) for DCI detection using the area under receiver operator characteristic (ROC) curve. Fifty-two patients treated with coil embolization were enrolled, including 18 with DCI (34.6%) and 34 without DCI (65.4%). Significant differences in rSO2 levels were observed from days 7 to 9. The rSO2 level was 60.95 (58.10–62.30) at day 7 in the DCI vs. 63.90 (62.50–67.10) in the non-DCI patients. By day 8, it was 59.50 (56.90–64.50) in the DCI vs. 63.30 (59.70–68.70) in the non-DCI cases. By day 9, it was 61.85 (59.40–65.20) in the DCI vs. 66.00 (62.70–68.30) in the non-DCI. A decline of >12.7% in SO2 rate yielded a sensitivity of 94.44% (95% CI: 72.7–99.9%) and a specificity of 70.59% (95% CI: 52.5–84.9%) for identifying DCI. Changes in NIRS tended to yield better diagnostic accuracy than TCD, but were not statistically significant. NIRS is a feasible method for real-time detection of DCI. Full article

(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Care and Diagnosis)

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Review

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16 pages, 255 KiB

Open AccessReview

Lessons from the CONSCIOUS-1 Study

by Alexander J. Schupper, Matthew E. Eagles, Sean N. Neifert, J Mocco and R. Loch Macdonald

J. Clin. Med. 2020, 9(9), 2970; https://doi.org/10.3390/jcm9092970 - 14 Sep 2020

Cited by 12 | Viewed by 2913

Abstract

After years of research on treatment of aneurysmal subarachnoid hemorrhage (aSAH), including randomized clinical trials, few treatments have been shown to be efficacious. Nevertheless, reductions in morbidity and mortality have occurred over the last decades. Reasons for the improved outcomes remain unclear. One [...] Read more.

After years of research on treatment of aneurysmal subarachnoid hemorrhage (aSAH), including randomized clinical trials, few treatments have been shown to be efficacious. Nevertheless, reductions in morbidity and mortality have occurred over the last decades. Reasons for the improved outcomes remain unclear. One randomized clinical trial that has been examined in detail with these questions in mind is Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1). This was a phase-2 trial testing the effect of clazosentan on angiographic vasospasm (aVSP) in patients with aSAH. Clazosentan decreased moderate to severe aVSP. There was no statistically significant effect on the extended Glasgow outcome score (GOS), although the study was not powered for this endpoint. Data from the approximately 400 patients in the study were detailed, rigorously collected and documented and were generously made available to one investigator. Post-hoc analyses were conducted which have expanded our knowledge of the management of aSAH. We review those analyses here. Full article

(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Care and Diagnosis)

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