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Subarachnoid Hemorrhage: Clinical Advances and Challenges
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Subarachnoid Hemorrhage: Clinical Advances and Challenges

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: 20 May 2025 | Viewed by 10776

Special Issue Editors

Prof. Dr. Tihamér Molnár

E-Mail Website
Guest Editor
Department of Anaesthesiology and Intensive Care, Medical School, University of Pecs, 7624 Pecs, Hungary
Interests: intensive care; subarachnoid hemorrhage; delayed cerebral ischemia; traumatic brain injury
Special Issues, Collections and Topics in MDPI journals
Dr. Péter Csécsei

E-Mail Website
Guest Editor
Department of Neurosurgery, University of Pecs, 7624 Pécs, Hungary
Interests: ischemic stroke; subarachnoid hemorrhage; vasospasm; thrombectomy; post-COVID; long COVID
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Subarachnoid hemorrhage (SAH), primarily caused by ruptured intracranial aneurysms, is a serious condition that causes severe disability primarily in young, productive adults. For decades, it has been treated with surgical arterial clipping or, more commonly, endovascular treatment. Cerebral vasospasm (CVS) is the most common complication after subarachnoid hemorrhage (SAH), and it is also an important cause of death and disability in SAH. Active prevention and treatment of CVS is the key to improving the prognosis of SAH.

The purpose of this Special Issue is to provide an up-to-date overview of the clinical diagnosis, treatment, and management of subarachnoid hemorrhage. We seek original, high-quality research papers, as well as review articles, that address major research challenges and achievements on the topic.

Prof. Dr. Tihamér Molnár
Dr. Péter Csécsei
Guest Editors

Manuscript Submission Information

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Keywords

  • subarachnoid hemorrhage
  • epidural and subdural hematomas
  • intracerebral and intraventricular hemorrhage
  • hemorrhagic stroke
  • cerebral infarction
  • hypertension
  • early brain damage
  • delayed cerebral vasospasm
  • neurobehavioral aspects
  • ruptured intracranial aneurysm
  • neuroinflammation
  • epidemiological studies
  • neuroimaging
  • clinical guidelines
  • neurocritical care management
  • surgery
  • new drug therapies
  • diagnosis
  • treatment
  • management
  • risk factors
  • prognosis
  • clinical outcome

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Published Papers (6 papers)

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19 pages, 9371 KiB  
Article
Diagnostic and Therapeutic Approaches for Spinal Subarachnoid Hemorrhage Due to Spinal Aneurysms and Other Etiologies
by Biyan Nathanael Harapan, Robert Forbrig, Thomas Liebig, Christian Schichor and Jun Thorsteinsdottir
J. Clin. Med. 2025, 14(7), 2398; https://doi.org/10.3390/jcm14072398 - 31 Mar 2025
Viewed by 442
Abstract
Background: Spinal subarachnoid hemorrhage (sSAH) is a very rare disease. Detailed information about the natural course, pathogenesis, radiological manifestation, and therapeutic management is lacking. This study aimed to analyze patients diagnosed with sSAH, focusing on the origin, management strategies, and therapeutic approaches [...] Read more.
Background: Spinal subarachnoid hemorrhage (sSAH) is a very rare disease. Detailed information about the natural course, pathogenesis, radiological manifestation, and therapeutic management is lacking. This study aimed to analyze patients diagnosed with sSAH, focusing on the origin, management strategies, and therapeutic approaches to sSAH. Methods: The study included a cohort of patients admitted to the Department of Neurosurgery, LMU University Hospital, LMU Munich, between January 2021 and December 2024 with a confirmed diagnosis of spinal subarachnoid hemorrhage and, among other things, spinal aneurysms. Data on the included patients were recorded with emphasis on demographics, radiological examination (CT, MRI, and DSA), aneurysm-specific characteristics, and clinical outcome. Results: The study included six patients diagnosed with spinal subarachnoid hemorrhage via multimodal imaging. The etiology of sSAH was identified in all cases, encompassing spinal aneurysms in three patients, anticoagulation therapy in two cases, and bony microspurs in one case, with management strategies tailored as either conservative (monitoring and imaging) or surgical (aneurysm resection, arterial feeder coagulation, or evacuation of intraspinal bleeding). No major adverse events were observed, and all the patients demonstrated neurological improvement or exhibited only mild-to-moderate disability during follow-up. Conclusions: Spinal subarachnoid hemorrhage can be due to a ruptured spinal aneurysm, but in some cases, other underlying causes should be considered as the source of the hemorrhage. Given the scarcity of literature on this condition, it is crucial to identify the correct diagnosis and implement a patient-tailored therapeutic approach. Full article
(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Advances and Challenges)
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9 pages, 1334 KiB  
Communication
Altered Pattern of Serum N-Glycome in Subarachnoid Hemorrhage and Cerebral Vasospasm
by Máté Czabajszki, Attila Garami, Tihamér Molnár, Péter Csécsei, Béla Viskolcz, Csaba Oláh and Csaba Váradi
J. Clin. Med. 2025, 14(2), 465; https://doi.org/10.3390/jcm14020465 - 13 Jan 2025
Viewed by 1346
Abstract
Background: Subarachnoid hemorrhage is a serious condition caused by ruptured intracranial aneurysms, resulting in severe disability mainly in young adults. Cerebral vasospasm is one of the most common complication of subarachnoid hemorrhage; thus, active prevention is key to improve the prognosis. The [...] Read more.
Background: Subarachnoid hemorrhage is a serious condition caused by ruptured intracranial aneurysms, resulting in severe disability mainly in young adults. Cerebral vasospasm is one of the most common complication of subarachnoid hemorrhage; thus, active prevention is key to improve the prognosis. The glycosylation of proteins is a critical quality attribute which is reportedly altered in patients diagnosed with acute ischemic stroke. In this study, we examined the N-glycosylation profile of serum glycoproteins in patients with subarachnoid hemorrhage without vasospasm compared to patients with vasospasm. Methods: The serum N-glycans were released by PNGase F (Peptide: N-glycosidase F) digestion and subsequently labeled by procainamide via reductive amination. The samples were analyzed by hydrophilic-interaction liquid chromatography after solid-phase extraction-based sample purification. Results: Besides the glycosylation pattern, we also investigated the biomarkers following subarachnoid hemorrhage. Multiple statistical analyses were performed in order to find significant differences and identify potential prediction factors of cerebral vasospasm. Significant differences were identified such as higher sialylation on bi-, tri-, and tetra-antennary structures in patients with subarachnoid hemorrhage and cerebral vasospasm. Conclusions: Our results suggest that glycosylation analysis can improve the identification of patients with cerebral vasospasm in combination with laboratory parameters. Full article
(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Advances and Challenges)
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12 pages, 3859 KiB  
Article
Correlation of Inflammatory Parameters with the Development of Cerebral Vasospasm, Takotsubo Cardiomyopathy, and Functional Outcome after Spontaneous Subarachnoid Hemorrhage
by Dorottya Szántó, Péter Luterán, Nikolett Kóti, Péter Siró, Éva Simon, Zsuzsa Jakab, Judit Gál, János Kappelmayer, Béla Fülesdi and Csilla Molnár
J. Clin. Med. 2024, 13(7), 1955; https://doi.org/10.3390/jcm13071955 - 28 Mar 2024
Cited by 1 | Viewed by 1286
Abstract
Background: The present work aimed to determine whether a relationship exists between inflammatory parameters and the development of vasospasm (VS) and Takotsubo cardiomyopathy (TTC), as well as clinical outcome, in patients suffering from spontaneous subarachnoid hemorrhage (SAH). Methods: In this study, the [...] Read more.
Background: The present work aimed to determine whether a relationship exists between inflammatory parameters and the development of vasospasm (VS) and Takotsubo cardiomyopathy (TTC), as well as clinical outcome, in patients suffering from spontaneous subarachnoid hemorrhage (SAH). Methods: In this study, the authors processed the prospectively collected laboratory and clinical data of spontaneous SAH patients admitted to the neurointensive care unit between March 2015 and October 2023. The highest values of neutrophils (NEUpeak), monocytes (MONOpeak), neutrophil-to-lymphocyte ratio (NLRpeak), and CRP (CRPpeak) during the initial 7 days were correlated with the occurrence of VS and TTC, and with the outcome measures at day 30 after onset. Results: Data were collected from 175 SAH patients. Based on ROC analysis, for the development of VS, MONOpeak was the most accurate indicator (AUC: 0.619, optimal cut-off: 1.45 G/L). TTC with severe left ventricular dysfunction (ejection fraction < 40%) was indicated most sensitively by NEUpeak (ROC: 0.763, optimal cut-off: 12.34 G/L). Both for GOS and Barthel Index at day 30, CRPpeak was the best predictor for the outcome (GOS: ROC: 0.846, optimal cut-off: 78.33 mg/L and Barthel Index: ROC: 0.819, optimal cut-off: 78.33 mg/L). Conclusions: Laboratory parameters referring to inflammation during the initial 7 days after SAH correlate with the development of VS and TTC, and thus may predict functional outcome. Full article
(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Advances and Challenges)
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11 pages, 228 KiB  
Article
External Ventricular Drain Placement, Critical Care Utilization, Complications, and Clinical Outcomes after Spontaneous Subarachnoid Hemorrhage: A Single-Center Retrospective Cohort Study
by Abhijit Vijay Lele, Christine T. Fong, Andrew M. Walters and Michael J. Souter
J. Clin. Med. 2024, 13(4), 1032; https://doi.org/10.3390/jcm13041032 - 11 Feb 2024
Cited by 2 | Viewed by 2137
Abstract
Background: To examine the association between external ventricular drain (EVD) placement, critical care utilization, complications, and clinical outcomes in hospitalized adults with spontaneous subarachnoid hemorrhage (SAH). Methods: A single-center retrospective study included SAH patients 18 years and older, admitted between 1 January 2014 [...] Read more.
Background: To examine the association between external ventricular drain (EVD) placement, critical care utilization, complications, and clinical outcomes in hospitalized adults with spontaneous subarachnoid hemorrhage (SAH). Methods: A single-center retrospective study included SAH patients 18 years and older, admitted between 1 January 2014 and 31 December 2022. The exposure variable was EVD. The primary outcomes of interest were (1) early mortality (<72 h), (2) overall mortality, (3) improvement in modified-World Federation of Neurological Surgeons (m-WFNSs) grade between admission and discharge, and (4) discharge to home at the end of the hospital stay. We adjusted for admission m-WFNS grade, age, sex, race/ethnicity, intraventricular hemorrhage, aneurysmal cause of SAH, mechanical ventilation, critical care utilization, and complications within a multivariable analysis. We reported adjusted odds ratios (aORs) and 95% confidence intervals (CI). Results: The study sample included 1346 patients: 18% (n = 243) were between the ages of 18 and 44 years, 48% (n = 645) were between the age of 45–64 years, and 34% (n = 458) were 65 years and older, with other statistics of females (56%, n = 756), m-WFNS I–III (57%, n = 762), m-WFNS IV–V (43%, n = 584), 51% mechanically ventilated, 76% White (n = 680), and 86% English-speaking (n = 1158). Early mortality occurred in 11% (n = 142). Overall mortality was 21% (n = 278), 53% (n = 707) were discharged to their home, and 25% (n = 331) improved their m-WFNS between admission and discharge. Altogether, 54% (n = 731) received EVD placement. After adjusting for covariates, the results of the multivariable analysis demonstrated that EVD placement was associated with reduced early mortality (aOR 0.21 [0.14, 0.33]), an improvement in m-WFNS grade (aOR 2.06 [1.42, 2.99]) but not associated with overall mortality (aOR 0.69 [0.47, 1.00]) or being discharged home at the end of the hospital stay (aOR 1.00 [0.74, 1.36]). EVD was associated with a higher rate of ventilator-associated pneumonia (aOR 2.32 [1.03, 5.23]), delirium (aOR 1.56 [1.05, 2.32]), and a longer ICU (aOR 1.33 [1.29;1.36]) and hospital length of stay (aOR 1.09 [1.07;1.10]). Critical care utilization was also higher in patients with EVD compared to those without. Conclusions: The study suggests that EVD placement in hospitalized adults with spontaneous subarachnoid hemorrhage (SAH) is associated with reduced early mortality and improved neurological recovery, albeit with higher critical care utilization and complications. These findings emphasize the potential clinical benefits of EVD placement in managing SAH. However, further research and prospective studies may be necessary to validate these results and provide a more comprehensive understanding of the factors influencing clinical outcomes in SAH. Full article
(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Advances and Challenges)
16 pages, 855 KiB  
Article
CLR (C-Reactive Protein to Lymphocyte Ratio) Served as a Promising Predictive Biomarker for Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage (aSAH): A Retrospective Cohort Study
by Ke Li, Dilaware Khan, Igor Fischer, Daniel Hänggi, Jan F. Cornelius and Sajjad Muhammad
J. Clin. Med. 2024, 13(4), 940; https://doi.org/10.3390/jcm13040940 - 6 Feb 2024
Cited by 3 | Viewed by 2010
Abstract
Background: Subarachnoid hemorrhage is a devastating disease. Even after state-of-the-art treatment patients suffer from complications, including cerebral vasospasm (CVS), delayed cerebral ischemia (DCI), and chronic hydrocephalus (CH) following aneurysmal subarachnoid hemorrhage (aSAH). The aim of our study is to identify the predictive [...] Read more.
Background: Subarachnoid hemorrhage is a devastating disease. Even after state-of-the-art treatment patients suffer from complications, including cerebral vasospasm (CVS), delayed cerebral ischemia (DCI), and chronic hydrocephalus (CH) following aneurysmal subarachnoid hemorrhage (aSAH). The aim of our study is to identify the predictive value of the C-reactive protein to lymphocyte ratio (CLR) for neurological functional outcome and complications after aSAH. Methods: We retrospectively analyzed a total of 166 aSAH patients who met the inclusion criteria enrolled in our study. Multivariate logistic regression analyses were performed to evaluate the independent risk factors. The predictive value of different models was compared by calculating the areas under the receiver operating characteristic (ROC) curve. Results: On-admission levels of CLR in patients with poor outcomes (6 months mRS 3–6), CVS, DCI, and CH were significantly higher than those in patients with good outcomes (6 months mRS 0–2), non-CVS, non-DCI, and non-CH. Multivariate logistic regression analysis revealed that admission CLR was independently associated with CVS (OR [95% CI] 2.116 [1.507–2.971]; p < 0.001), and DCI (OR [95% CI] 1.594 [1.220–2.084]; p = 0.001). In ROC analysis, the area under the curve (AUC) of CLR for poor outcomes (6 months mRS 3–6), CVS, DCI, and CH prediction were (AUC [95% CI] 0.639 [0.555–0.724]; p = 0.002), (AUC [95% CI] 0.834 [0.767–0.901]; p < 0.001), (AUC [95% CI] 0.679 [0.581–0.777]; p < 0.001), and (AUC [95% CI] 0.628 [0.543–0.713]; p = 0.005) revealing that admission CLR had a favorable predictive value for CVS after aSAH. The sensitivity and specificity of admission CLR for CVS prediction were 77.1% and 75.4%. On-admission CLR of 0.757 mg × 10−6 was identified as the best cutoff threshold to discriminate between CVS and non-CVS (CVS: CLR < 0.757 mg × 10−6 11/100 [11.0%] vs. CLR ≥ 0.757 mg × 10−6 37/66 [56.1%]; p < 0.001). Conclusions: High levels of on-admission CLR serve as an independent risk factor for CVS and DCI after aSAH. Admission CLR is an easy-to-quantify laboratory parameter that efficiently predicts the CVS after aSAH, which can provide some guidance for clinicians to evaluate for possible progression and treatment strategies in patients with aSAH. Full article
(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Advances and Challenges)
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12 pages, 1924 KiB  
Systematic Review
A Long-Term Comparative Analysis of Endovascular Coiling and Clipping for Ruptured Cerebral Aneurysms: An Individual Patient-Level Meta-Analysis Assessing Rerupture Rates
by Johannes Wach, Martin Vychopen, Agi Güresir, Alexandru Guranda, Ulf Nestler and Erdem Güresir
J. Clin. Med. 2024, 13(6), 1778; https://doi.org/10.3390/jcm13061778 - 20 Mar 2024
Cited by 5 | Viewed by 2513
Abstract
Background: Although the initial functional outcome findings of the International Subarachnoid Aneurysm Trial (ISAT) study favored coiling at one year after aneurysmal subarachnoid hemorrhage (aSAH), concerns arose regarding limited long-term rerupture data. This meta-analysis is the first to analyze longitudinal individual patient data [...] Read more.
Background: Although the initial functional outcome findings of the International Subarachnoid Aneurysm Trial (ISAT) study favored coiling at one year after aneurysmal subarachnoid hemorrhage (aSAH), concerns arose regarding limited long-term rerupture data. This meta-analysis is the first to analyze longitudinal individual patient data (IPD) of target aneurysm rerupture in terms of treatment modality. Methods: The present meta-analysis included studies that compared clipping with coiling of ruptured aneurysms regarding long-term rerupture. Rerupture rates’ individual patient data (IPD) were extracted from published Kaplan–Meier curves utilizing the R package IPDfromKM in R Version 4.3.1. Results: A total of 3153 patients from two studies were included. The clipping arm included 1755 patients, whereas the coiling arm included 1398 patients. Median reconstructed follow-up was 6.1 years (IQR = 0.5–11.7). The rerupture rates in the clipping arm and the coiling arm were 0.5% and 1.5%, respectively (p = 0.002). Kaplan–Meier chart analysis of the 3153 patients revealed a shortened time to rerupture in the coiling arm (log-rank test: p = 0.01). The hazard ratio (HR) for coiling compared with clipping regarding rerupture was 3.62 (95% CI:1.21–10.86, p = 0.02). Conclusion: Target aneurysm rerupture was rare beyond the initial year. Pooled long-term IPD from the 3153 patients revealed that reruptures of target aneurysms are more common after coiling and might be considered in the pretherapeutic decision-making process for aSAH. Full article
(This article belongs to the Special Issue Subarachnoid Hemorrhage: Clinical Advances and Challenges)
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