ABSTRACT
BACKGROUND: Carotid siphon calcification (CSC) serves as a marker of atherosclerosis and therefore may influence the outcome after subarachnoid hemorrhage (aSAH). We aimed to analyze the impact of CSC on neurological outcomes, ischemia, and vasospasm. METHODS: A total of 716 patients with aSAH were treated between December 2004 and June 2016 in our central European tertiary neurovascular care center in Essen, Germany. CSC was recorded using the Woodcock scale (grades 0-3) on a computed tomography scan. Study end points included an unfavorable outcome at 6 months post-aSAH (modified Rankin Scale score ≥4), vasospasm, and early cerebral ischemia (72 hours) and delayed cerebral ischemia (delayed cerebral ischemia; >72 hours) in the follow-up computed tomography scans. The associations were adjusted for patients' baseline characteristics and secondary complications. Finally, within a subgroup analysis, patients with and without daily aspirin intake after endovascular aneurysm occlusion were compared. RESULTS: Increasing grades of CSC were associated with lower rates of vasospasm in the anterior circulation. Severe CSC (grade 3) was independently related to the risk of an unfavorable outcome (adjusted odds ratio [aOR], 4.06 [95% CI, 1.98-8.33]; P<0.001) and early cerebral ischemia (aOR, 1.58 [95% CI, 1.03-2.43]; P=0.035) but not delayed cerebral ischemia (aOR, 1.08 [95% CI, 0.67-1.73]; P=0.763). In the aspirin subgroup analysis, the negative effect of severe CSC on functional outcome remained significant only in aSAH cases without aspirin (aOR, 5.47 [95% CI, 2.38-12.54]; P<0.001). In contrast, there was no association between severe CSC and unfavorable outcomes among individuals with daily aspirin intake (aOR, 0.84 [95% CI, 0.59-4.21]; P=0.603). CONCLUSIONS: Our data suggest CSC as a cerebrovascular risk factor resulting in higher rates of early cerebral ischemia and unfavorable outcomes after aSAH. However, by increasing arterial stiffness, CSC might lower the probability of vasospasm, which could explain the missing link between CSC and delayed cerebral ischemia. Additionally, aspirin intake seems to potentially mitigate the negative impact of CSC on aSAH outcome. Further investigations are needed to confirm the observations from the present study.
ABSTRACT
OBJECTIVE: Elevation of Troponin I (TnI) in spontaneous subarachnoid hemorrhage (SAH) patients is a well-known phenomenon and associated with cardiopulmonary complications and poor outcome. The present study was conducted to investigate the association of the TnI value on admission, and the occurrence of cerebral vasospam in SAH patients. PATIENTS AND METHODS: A total of 142 patients with SAH, who were admitted to the neurosurgical intensive care unit (ICU) between December 2014 and January 2021 were evaluated. Blood samples were drawn on admission to determine TnI value. Each patient's demographic, radiological and medical data on admission, the modified Ranking Scale score at discharge as well as continuous measurements of transcranial Doppler sonography were analyzed. A maximum mean flow velocity (MMFV) > 120â cm/sec was defined as any vasospasm. These were stratified into severe vasospasms, which were defined as at least two measurements of MMFVs > 200â cm/sec or an increase of MMFV > 50â cm/sec/24â h over two consecutive days or a new neurological deterioration and mild vasospasm defined as MMFVs > 120â cm/sec in absence of severe vasospasm criteria. The total study population was dichotomized into patients with an initially elevated TnI (>0.05â µg/L) and without elevated TnI (≤0.05â µg/L). RESULTS: A total of 52 patients (36.6%) had an elevated TnI level upon admission, which was significantly associated with lower GCS score (p < 0.001), higher WFNS score (p < 0.001) and higher Fisher grade (p = 0.01) on admission. In this context a higher rate of ischemic brain lesions (p = 0.02), a higher modified Rankin Scale score (p > 0.001) and increased mortality (p = 0.02) at discharge were observed in this group. In addition, TnI was identified as an independent predictor for the occurrence of any vasospasm and severe vasospasm. CONCLUSION: An initially elevated TnI level is an independent predictor for the occurrence of any and severe vasospasm in patients with SAH.
ABSTRACT
Preterm neonates are at risk for neurodevelopmental impairment, especially those with intraventricular hemorrhage (IVH). Cerebral vasospasm (VSP) is a common complication after subarachnoid hemorrhage (SAH) in adult population, but it is unknown if preterm neonates with IVH may develop it. We prospectively enrolled premature newborns < 32 weeks with IVH and without IVH. All patients received serial transcranial sonography through the temporal window of the middle cerebral artery, anterior cerebral artery, posterior cerebral artery, and the internal carotid artery with transcranial Doppler sonography days 2, 4, and 10 of life. Cerebral blood velocities (CBFVs) were measured including median velocity flow (MV), peak systolic velocity (PSV), and maximum end-diastolic velocity (EDV). Resistance index and pulsatility index were calculated. VSP was defined as an increase of 50% in the baseline velocity per day and/or a Lindegaard ratio higher than 3. Fifty subjects were enrolled. None of the patients with IVH showed elevation of MV or a Lindegaard ratio > 3. There were no differences between IVH and without IVH groups regarding resistance index and pulsatility index. Conclusion: Preterm infants with IVH do not present a pattern of VSP analyzed by Doppler transcranial ultrasound in this pilot study. What is Known: ⢠In adult population with subarachnoid hemorrhage the most treatable cause of cerebral ischemia is due cerebral vasospasm but is unknown if premature newborn may have vasospasm due the extravasation of blood in the context of intraventricular hemorrhage What is New: â¢In this pilot study we did not find in premature newborn with intraventricular hemorrhage signs of vasoespam measured by transcranial color doppler ultrasound.
Subject(s)
Infant, Premature , Ultrasonography, Doppler, Transcranial , Vasospasm, Intracranial , Humans , Pilot Projects , Infant, Newborn , Ultrasonography, Doppler, Transcranial/methods , Vasospasm, Intracranial/diagnostic imaging , Vasospasm, Intracranial/etiology , Vasospasm, Intracranial/physiopathology , Female , Male , Prospective Studies , Infant, Premature, Diseases/diagnostic imaging , Infant, Premature, Diseases/physiopathology , Cerebrovascular Circulation/physiology , Blood Flow Velocity/physiology , Cerebral Intraventricular Hemorrhage/diagnostic imaging , Cerebral Intraventricular Hemorrhage/etiologyABSTRACT
PURPOSE: Transcranial doppler based diagnostic criteria for cerebral vasospasm are not well established in the pediatric population because there is no published normative data to support the diagnosis. Studies have relied on expert consensus, but the definitions have not been validated in children diagnosed with angiographic evidence of vasospasm. Obtaining normative data is a prerequisite to defining pediatric cerebral vasospasm and the Lindegaard Ratio (LR). In this study, we obtained normative data and calculation of the normal LR from healthy children aged 10-16 years. METHODS: TCD and carotid ultrasonography was used to measure steady state velocities of both the middle cerebral artery (VMCA) and the extracranial internal cerebral artery (VEICA) in healthy children aged 10-16 years. Demographic information, hemodynamic characteristics and the calculated LR (VMCA/VEICA) was determined for each subject using descriptive statistics. RESULTS: Of the 26 healthy children, 13 were male and 13 were female. VMCA ranged between 53 and 93 cm/sec. LR ranged between 1 and 2.2 for the cohort. VMCA for both males and females were within 2 standard deviations (SD) of the normal mean flow velocity. As the VMCA velocities approached 2 SD above the mean, LR did not exceed 2.2. CONCLUSION: Our results help define a threshold for LR which can be used to establish radiographic criteria for cerebral vasospasm in children. Our data suggests that using VMCA criteria alone would overestimate cerebral vasospasm and raises question of whether an LR threshold other than 3 is more appropriate for the cut off between hyperemia versus vasospasm in children.
Subject(s)
Ultrasonography, Doppler, Transcranial , Humans , Child , Female , Male , Adolescent , Ultrasonography, Doppler, Transcranial/methods , Reference Values , Middle Cerebral Artery/diagnostic imaging , Blood Flow Velocity/physiology , Vasospasm, Intracranial/diagnostic imaging , Cerebrovascular Circulation/physiologyABSTRACT
This letter commends the article by Luzzi et al. on alternative neuroprotection strategies for aneurysmal subarachnoid hemorrhage (SAH). It highlights the pharmacological advantages of nicardipine, cilostazol, and clazosentan over nimodipine in managing cerebral vasospasm and delayed cerebral ischemia. Emphasizing the need for personalized medicine, it advocates for integrating genetic screening and advanced monitoring techniques to tailor treatments to individual patient profiles. This approach could significantly improve clinical outcomes by optimizing drug efficacy and minimizing adverse effects.
Subject(s)
Brain Ischemia , Neuroprotective Agents , Nimodipine , Subarachnoid Hemorrhage , Vasospasm, Intracranial , Humans , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/drug therapy , Vasospasm, Intracranial/drug therapy , Vasospasm, Intracranial/prevention & control , Vasospasm, Intracranial/etiology , Nimodipine/therapeutic use , Brain Ischemia/drug therapy , Brain Ischemia/prevention & control , Neuroprotective Agents/therapeutic use , Nicardipine/therapeutic use , Neuroprotection/drug effects , Cilostazol/therapeutic use , Dioxanes/therapeutic use , Vasodilator Agents/therapeutic use , Pyridines/therapeutic use , Pyrimidines , Sulfonamides , TetrazolesABSTRACT
Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Considering the significance of this matter and a lack of effective prophylaxis against DCI, we aim to summarize the current state of knowledge regarding their associations with DNA methylation and identify the gaps for a future trial. PubMed MEDLINE, Scopus, and Web of Science were searched by two authors in three waves for relevant DNA methylation association studies in DCI after aSAH. PRISMA checklist was followed for a systematic structure. STROBE statement was used to assess the quality and risk of bias within studies. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 70 records, 7 peer-reviewed articles met the eligibility criteria. Five studies used a candidate gene approach, three were epigenome-wide association studies (EWAS), one utilized bioinformatics of the previous EWAS, with two studies using more than one approach. Methylation status of four cytosine-guanine dinucleotides (CpGs) related to four distinct genes (ITPR3, HAMP, INSR, CDHR5) have been found significantly or suggestively associated with DCI after aSAH. Analysis of epigenetic clocks yielded significant association of lower age acceleration with radiological CVS but not with DCI. Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis. As none of the CpGs overlapped across the studies, meta-analysis was not applicable. The identified methylation sites might potentially serve as a biomarker for early diagnosis of DCI after aSAH in future. However, a lack of overlapping results prompts the need for large-scale multicenter studies. Challenges and prospects are discussed.
Subject(s)
Brain Ischemia , Subarachnoid Hemorrhage , Vasospasm, Intracranial , Humans , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/genetics , DNA Methylation , Cerebral Infarction/complications , Brain Ischemia/genetics , Brain Ischemia/complications , Biomarkers , Vasospasm, Intracranial/genetics , Vasospasm, Intracranial/complications , Cadherin Related ProteinsABSTRACT
The clinical management of aneurysmal subarachnoid hemorrhage (SAH)-associated vasospasm remains a challenge in neurosurgical practice, with its prevention and treatment having a major impact on neurological outcome. While considered a mainstay, nimodipine is burdened by some non-negligible limitations that make it still a suboptimal candidate of pharmacotherapy for SAH. This narrative review aims to provide an update on the pharmacodynamics, pharmacokinetics, overall evidence, and strength of recommendation of nimodipine alternative drugs for aneurysmal SAH-associated vasospasm and delayed cerebral ischemia. A PRISMA literature search was performed in the PubMed/Medline, Web of Science, ClinicalTrials.gov, and PubChem databases using a combination of the MeSH terms "medical therapy," "management," "cerebral vasospasm," "subarachnoid hemorrhage," and "delayed cerebral ischemia." Collected articles were reviewed for typology and relevance prior to final inclusion. A total of 346 articles were initially collected. The identification, screening, eligibility, and inclusion process resulted in the selection of 59 studies. Nicardipine and cilostazol, which have longer half-lives than nimodipine, had robust evidence of efficacy and safety. Eicosapentaenoic acid, dapsone and clazosentan showed a good balance between effectiveness and favorable pharmacokinetics. Combinations between different drug classes have been studied to a very limited extent. Nicardipine, cilostazol, Rho-kinase inhibitors, and clazosentan proved their better pharmacokinetic profiles compared with nimodipine without prejudice with effective and safe neuroprotective role. However, the number of trials conducted is significantly lower than for nimodipine. Aneurysmal SAH-associated vasospasm remains an area of ongoing preclinical and clinical research where the search for new drugs or associations is critical.
Subject(s)
Brain Ischemia , Neuroprotective Agents , Nimodipine , Subarachnoid Hemorrhage , Vasospasm, Intracranial , Humans , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/drug therapy , Vasospasm, Intracranial/drug therapy , Vasospasm, Intracranial/etiology , Nimodipine/therapeutic use , Brain Ischemia/drug therapy , Neuroprotective Agents/therapeutic use , Neuroprotection/drug effects , Cilostazol/therapeutic use , Nicardipine/therapeutic use , Dioxanes/therapeutic use , Vasodilator Agents/therapeutic use , Pyrimidines/therapeutic use , Pyridines , Sulfonamides , TetrazolesABSTRACT
Nimodipine dose reduction is recommended in case of high vasopressor demand after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to assess potential adverse effects of nimodipine reduction during the high-risk period for delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) between days 5 and 10 after hemorrhage. Demographic and clinical data as well as daily nimodipine dose of aSAH patients admitted between 2010 and 2019 were retrospectively analyzed. Univariable and multivariable regression analyses were performed to identify factors associated with DCI, angiographic CVS, DCI-related infarction, and unfavorable outcome. A total of 205 patients were included. Nimodipine dose reduction occurred in 108 (53%) patients ('nimodipine reduction group'), while 97 patients (47%) received the full dose ('no nimodipine reduction group'), Patients in the 'nimodipine reduction group' had significant worse WFNS and Fisher grades and developed significantly more often DCI and angiographic CVS. DCI-related infarction and unfavorable outcome were also significantly increased in the 'nimodipine reduction group.' 'Reduced nimodipine dose' was the only independent predictor for the occurrence of DCI and angiographic CVS in multivariable regression analysis. 'Poor WFNS grade' and 'reduced nimodipine dose' were identified as independent risk factors for DCI-related infarction while 'older age,' 'poor WFNS grade,' and 'reduced nimodipine dose' were associated with unfavorable outcome at 3 months after discharge. Nimodipine dose reduction during the high-risk period of DCI and CVS between days 5 and 10 after hemorrhage might abrogate the positive prognostic effects of nimodipine and should be critically evaluated.
Subject(s)
Subarachnoid Hemorrhage , Vasospasm, Intracranial , Humans , Nimodipine/therapeutic use , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/drug therapy , Subarachnoid Hemorrhage/surgery , Drug Tapering , Retrospective Studies , Cerebral Infarction/drug therapy , Cerebral Infarction/etiology , Vasospasm, Intracranial/drug therapy , Vasospasm, Intracranial/etiologyABSTRACT
This critique discusses neuroprotective strategies for aneurysmal subarachnoid hemorrhage (SAH), excluding Nimodipine, emphasizing alternatives like verapamil, albumin, and cilostazol. While these options show potential, their efficacy lacks robust confirmation from randomized controlled trials (RCTs), relying mainly on observational studies and small trials. The letter underscores the need for comprehensive safety assessments and long-term outcome studies to enhance practical application. Highlighting ongoing trials and emerging therapies like clazosentan and TAK-044, it advocates for future research directions focused on large-scale RCTs and combination therapies, such as cilostazol and Nimodipine, which have demonstrated synergistic benefits in reducing delayed cerebral ischemia (DCI) and improving patient outcomes.
Subject(s)
Brain Ischemia , Neuroprotective Agents , Nimodipine , Subarachnoid Hemorrhage , Vasospasm, Intracranial , Humans , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/drug therapy , Vasospasm, Intracranial/drug therapy , Vasospasm, Intracranial/prevention & control , Vasospasm, Intracranial/etiology , Nimodipine/therapeutic use , Neuroprotective Agents/therapeutic use , Brain Ischemia/drug therapy , Brain Ischemia/prevention & control , Neuroprotection/drug effects , Cilostazol/therapeutic useABSTRACT
PURPOSE: Intrathecal vasoactive drugs have been proposed in patients with aneurysmal subarachnoid hemorrhage (aSAH) to manage cerebral vasospasm (CV). We analyzed the efficacy of intracisternal nicardipine compared to intraventricular administration to a control group (CG) to determine its impact on delayed cerebral ischemia (DCI) and functional outcomes. Secondary outcomes included the need for intra-arterial angioplasties and the safety profile. METHODS: We performed a retrospective analysis of prospectively collected data of all adult patients admitted for a high modified Fisher grade aSAH between January 2015 and April 2022. All patients with significant radiological CV were included. Three groups of patients were defined based on the CV management: cisternal nicardipine (CN), ventricular nicardipine (VN), and no intrathecal nicardipine (control group). RESULTS: Seventy patients met the inclusion criteria. Eleven patients received intracisternal nicardipine, 18 intraventricular nicardipine, and 41 belonged to the control group. No cases of DCI were observed in the CN group (p = 0.02). Patients with intracisternal nicardipine had a reduced number of intra-arterial angioplasties when compared to the control group (p = 0.03). The safety profile analysis showed no difference in complications across the three groups. Intrathecal (ventricular or cisternal) nicardipine therapy improved functional outcomes at 6 months (p = 0.04) when compared to the control group. CONCLUSION: Administration of intrathecal nicardipine for moderate to severe CV reduces the rate of DCI and improved long-term functional outcomes in patients with high modified Fisher grade aSAH. This study also showed a relative benefit of cisternal over intraventricular nicardipine, thereby reducing the number of angioplasties performed in the post-treatment phase. However, these preliminary results should be confirmed with future prospective studies.
Subject(s)
Brain Ischemia , Subarachnoid Hemorrhage , Vasospasm, Intracranial , Adult , Humans , Nicardipine , Subarachnoid Hemorrhage/complications , Retrospective Studies , Prospective Studies , Brain Ischemia/drug therapy , Cerebral Infarction , Vasospasm, Intracranial/etiologyABSTRACT
Cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH) remains one of the leading causes of high mortality and poor outcomes. Understanding the risk factors associated with CV is pivotal to improving patients' outcomes. We conducted an extensive search for analytical observational studies that analyzed the correlation between various variables and the likelihood of CV development among adult patients with SAH (age ≥ 18 years). Five scholar databases were used, namely, PubMed, EBSCO, Web of Science, Science Direct, and Google Scholar. Relevant studies published between January 1st, 2016, and August 9th, 2023, were included. The Newcastle-Ottawa Scale was adopted to assess the risk of bias among included observational studies. A total of 33 studies met the inclusion criteria. Of the 24,958 patients with SAH who were identified, 6,761 patients had a subsequent CV (27.1%). Several statistically significant risk factors were reported across the literature. Younger age, female sex, smoking, alcohol intake, modified Fisher grade 3-4, higher Hunt and Hess grading, and the presence of multiple comorbidities (diabetes, hypertension, congestive heart failure, and history of stroke) were among the well-established risk factors for CV. Additionally, leukocytosis was consistently reported to be a significant predictor in multiple studies, providing compelling evidence for its association with CV. Even though single studies reported an association between CV and certain variables, further research is necessary to investigate the implications of these findings. These include arterial tortuosity, hypokalemia, potassium to glucose gradient, hypoalbuminemia, anemia, von Willebrand factor and vascular endothelial growth factor, use of desflurane, and hemodynamic stability. Overall, this systemic review provides a comprehensive summary of the current data that evaluates the potential risk factors for the development of CV after SAH. However, because of data heterogeneity, certain factors require further validation in their correlation with CV development. Larger-scale observational and clinical trials are mandatory to extensively investigate the significant predictors of CV to lay the scientific foundation for improving outcomes in susceptible patients with SAH.
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OBJECTIVES: Vasospasm is a complication of aneurysmal subarachnoid hemorrhage (aSAH) that can change the trajectory of recovery and is associated with morbidity and mortality. Earlier detection of vasospasm could improve patient outcomes. Our objective is to evaluate the accuracy of smartphone-based quantitative pupillometry in the detection of radiographic vasospasm and delayed cerebral ischemia (DCI) after aSAH. MATERIALS AND METHODS: We prospectively collected pupillary light reflex (PLR) parameters from patients with aSAH admitted to a neurocritical care unit at a single hospital twice daily using quantitative smartphone pupillometry recordings. PLR parameters included: Maximum pupil diameter, minimum pupil diameter, percent change in pupil diameter, latency in beginning of pupil constriction to light, mean constriction velocity, maximum constriction velocity, and mean dilation velocity. Two-tailed t-tests for independent samples were performed to determine changes in average concurrent PLR parameter values between the following comparisons: (1) patients with and without radiographic vasospasm (defined by angiography with the need for endovascular intervention) and (2) patients with and without DCI. RESULTS: 49 subjects with aSAH underwent 323 total PLR recordings. For PLR recordings taken with (n=35) and without (n=241) radiographic vasospasm, significant differences were observed in MIN (35.0 ± 7.5 pixels with vasospasm versus 31.6 ± 6.2 pixels without; p=0.002). For PLR recordings taken with (n=43) and without (n=241) DCI, significant differences were observed in MAX (48.9 ± 14.3 pixels with DCI versus 42.5 ± 9.2 pixels without; p<0.001). CONCLUSIONS: Quantitative smartphone pupillometry has the potential to be used to detect radiographic vasospasm and DCI after aSAH.
ABSTRACT
Clazosentan has been shown to prevent vasospasm and reduce mortality in patients after aneurysmal subarachnoid hemorrhage (SAH) and has been approved for clinical use in Japan; however, its systemic events in the elderly (aged ≥ 75 years) have not been well-documented. Here, we report serious/intolerable cardiopulmonary complications requiring discontinuation of drug therapy in elderly SAH patients. In this single-center case series study, medical records of consecutive SAH patients treated postoperatively with clazosentan (10 mg/h) between June 2022 and May 2023 were reviewed retrospectively. Thirty-three patients received clazosentan therapy, of whom six were elderly with a mean age of 80.3 ± 5.2 (range 75-89) years. Among them, despite no obvious medical history of systemic abnormalities, clazosentan was discontinued in three (50%) patients due to pleural effusion and hypoxemia with or without hypotension at 5 ± 3 days after therapy initiation, which was higher than the incidence for younger patients (15%). The elderly patients had significantly lower urine output (1935 ± 265 vs. 1123 ± 371 mL/day, p = 0.03) and greater weight gain (2.1 ± 1.1 vs. 4.2 ± 1.9 kg from baseline, p = 0.04) than patients who completed the therapy. One 89-year-old female developed congestive heart failure and hydrostatic pulmonary edema associated with increased intravascular and lung volumes even after therapy was discontinued, while the remaining two cases recovered within 2 days after drug cessation. These results suggest that elderly patients are more vulnerable to fluid retention and have a higher risk of cardiopulmonary complications during clazosentan therapy than younger patients. Careful monitoring of urine volume and weight gain and caution regarding age- and therapy-related hemodynamic insufficiencies are required.
Subject(s)
Dioxanes , Pyridines , Pyrimidines , Stroke , Subarachnoid Hemorrhage , Sulfonamides , Tetrazoles , Vasospasm, Intracranial , Aged , Female , Humans , Aged, 80 and over , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/drug therapy , Retrospective Studies , Japan/epidemiology , Stroke/complications , Weight GainSubject(s)
Brain Ischemia , Neuroprotective Agents , Nimodipine , Subarachnoid Hemorrhage , Vasospasm, Intracranial , Vasospasm, Intracranial/drug therapy , Vasospasm, Intracranial/etiology , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/drug therapy , Humans , Nimodipine/therapeutic use , Brain Ischemia/drug therapy , Neuroprotective Agents/therapeutic use , NeuroprotectionABSTRACT
Introduction: Patients who suffer severe traumatic brain injury (sTBI) and cerebral vasospasm (CVS) frequently have posttraumatic cerebral ischemia (PCI). The research question: was to study changes in cerebral microcirculatory bed parameters in sTBI patients with CVS and with or without PCI. Material and methods: A total of 136 severe TBI patients were recruited in the study. All patients underwent perfusion computed tomography, intracranial pressure monitoring, and transcranial Doppler. The levels of cerebrovascular resistance (CVR), cerebral arterial compliance (CAC), cerebrovascular time constant (CTC), and critical closing pressure (CCP) were measured using the neuromonitoring complex. Statistical analysis was performed using parametric and nonparametric methods and factor analysis. The patients were dichotomized into PCI-positive (n = 114) and PCI-negative (n = 22) groups. Data are presented as mean values (standard deviations). Results: CVR was significantly increased, whereas CAC, CTC, and CCP were significantly decreased in sTBI patients with CVS and PCI development (p < 0.05). Factor analyses revealed that all studied microcirculatory bed parameters were significantly associated with the development of PCI (p < 0.05). Discussion and conclusion: The changes in all studied microcirculatory bed parameters in TBI patients with CVS were significantly associated with PCI development, which enables us to regard them as the biomarkers of CVS and PCI development. The causes of the described microcirculatory bed parameters changes might include complex (cytotoxic and vasogenic) brain edema development, regional microvascular spasm, and dysfunction of pericytes. A further prospective study is warranted.
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BACKGROUND: Cerebral vasospasm (CV) is a feared complication which occurs after 20-40% of subarachnoid haemorrhage (SAH). It is standard practice to admit patients with SAH to intensive care for an extended period of resource-intensive monitoring. We used machine learning to predict CV requiring verapamil (CVRV) in the largest and only multi-center study to date. METHODS: Patients with SAH admitted to UCLA from 2013 to 2022 and a validation cohort from VUMC from 2018 to 2023 were included. For each patient, 172 unique intensive care unit (ICU) variables were extracted through the primary endpoint, namely first verapamil administration or no verapamil. At each institution, a light gradient boosting machine (LightGBM) was trained using five-fold cross validation to predict the primary endpoint at various hospitalization timepoints. FINDINGS: A total of 1750 patients were included from UCLA, 125 receiving verapamil. LightGBM achieved an area under the ROC (AUC) of 0.88 > 1 week in advance and ruled out 8% of non-verapamil patients with zero false negatives. Our models predicted "no CVRV" vs "CVRV within three days" vs "CVRV after three days" with AUCs = 0.88, 0.83, and 0.88, respectively. From VUMC, 1654 patients were included, 75 receiving verapamil. VUMC predictions averaged within 0.01 AUC points of UCLA predictions. INTERPRETATION: We present an accurate and early predictor of CVRV using machine learning with multi-center validation. This represents a significant step towards optimized clinical management and resource allocation in patients with SAH. FUNDING: Robert E. Freundlich is supported by National Center for Advancing Translational Sciences federal grant UL1TR002243 and National Heart, Lung, and Blood Institute federal grant K23HL148640; these funders did not play any role in this study. The National Institutes of Health supports Vanderbilt University Medical Center which indirectly supported these research efforts. Neither this study nor any other authors personally received financial support for the research presented in this manuscript. No support from pharmaceutical companies was received.
Subject(s)
Machine Learning , Subarachnoid Hemorrhage , Vasospasm, Intracranial , Verapamil , Humans , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/diagnosis , Vasospasm, Intracranial/etiology , Vasospasm, Intracranial/diagnosis , Female , Male , Middle Aged , Verapamil/therapeutic use , Aged , ROC Curve , Adult , Prognosis , Intensive Care UnitsABSTRACT
Purpose: Cerebral vasospasm (CVS) is a common complication that occurs after neurosurgical clipping of intracranial aneurysms in patients with aSAH. This complication can lead to clinical deterioration and a poor prognosis. The aim of this study is to explore the risk factors for CVS in aSAH patients who have undergone neurosurgical clipping, develop a nomogram for CVS, and evaluate its performance. Methods: Patients with aSAH who underwent neurosurgical clipping in the Department of Neurosurgery from January 2018 to January 2023 were selected as the subjects of this research. The clinical data of these patients were retrospectively analyzed. Logistic multivariate regression analysis was employed to identify the independent risk factors of CVS. A clinical prediction model in the form of a nomogram for CVS was developed using the R programming language and subsequently evaluated for its performance and quality. Results: A total of 156 patients with aSAH were included in the analysis, comprising 109 patients in the training set and 47 patients in the validation set. In the training cohort, 27 patients (24.77%) developed CVS after neurosurgical clipping, while in the validation cohort, 15 patients (31.91%) experienced CVS. Multivariate regression analysis revealed that age, Hcy, WBC, glucose/potassium ratio, aneurysm location, and modified Fisher grade were independent risk factors for CVS. The nomogram exhibited excellent discriminative performance in both the training set (AUC = 0.885) and the validation set (AUC = 0.906). Conclusion: CVS was a prevalent complication following neurosurgical clipping in patients with aSAH, with a highly intricate pathogenesis and pathophysiological course. Early prediction of CVS represented a significant challenge in clinical practice. In this study, age, Hcy, WBC, glucose/potassium ratio, aneurysm location, and modified Fisher grade emerged as independent risk factors for CVS. The resulting nomogram demonstrated substantial predictive value.
ABSTRACT
Subarachnoid hemorrhage (SAH) remains a major cause of cerebrovascular morbidity, eliciting severe headaches and vasospasms that have been shown to inversely correlate with vasodilator calcitonin gene-related peptide (CGRP) levels. Although dura mater trigeminal afferents are an important source of intracranial CGRP, little is known about the effects of SAH on these neurons in preclinical models. The present study evaluated changes in CGRP levels and expression in trigeminal primary afferents innervating the dura mater 72 h after experimentally induced SAH in adult rats. SAH, eliciting marked damage revealed by neurological examination, significantly reduced the density of CGRP-immunoreactive nerve fibers both in the dura mater and the trigeminal caudal nucleus in the medulla but did not affect the total dural nerve fiber density. SAH attenuated ex vivo dural CGRP release by ~40% and in the trigeminal ganglion, reduced both CGRP mRNA levels and the number of highly CGRP-immunoreactive cell bodies. In summary, we provide novel complementary evidence that SAH negatively affects the integrity of the CGRP-expressing rat trigeminal neurons. Reduced CGRP levels suggest likely impaired meningeal neurovascular functions contributing to SAH complications. Further studies are to be performed to reveal the importance of impaired CGRP synthesis and its consequences in central sensory processing.
Subject(s)
Calcitonin Gene-Related Peptide , Dura Mater , Neurons , Rats, Sprague-Dawley , Subarachnoid Hemorrhage , Trigeminal Ganglion , Animals , Calcitonin Gene-Related Peptide/metabolism , Dura Mater/metabolism , Male , Rats , Subarachnoid Hemorrhage/metabolism , Subarachnoid Hemorrhage/pathology , Neurons/metabolism , Trigeminal Ganglion/metabolism , RNA, Messenger/metabolism , RNA, Messenger/genetics , Trigeminal Nerve/metabolismABSTRACT
Ultrasound evaluation of the brain is performed through acoustic windows. Transcranial Doppler has long been used to monitor patients with subarachnoid hemorrhage for cerebral vasospasm. Transcranial color-coded sonography permits parenchymal B-mode imaging and duplex evaluation. Transcranial ultrasound may also be used to assess the risk of delayed cerebral ischemia, screen patients for the presence of elevated intracranial pressure, confirm the diagnosis of brain death, measure midline shift, and detect ventriculomegaly. Transcranial ultrasound should be integrated with other point-of-care ultrasound techniques as an essential skill for the neurointensivist.
Subject(s)
Brain Ischemia , Subarachnoid Hemorrhage , Vasospasm, Intracranial , Humans , Subarachnoid Hemorrhage/diagnostic imaging , Ultrasonography, Doppler, Transcranial/methods , Vasospasm, Intracranial/diagnostic imaging , BrainABSTRACT
BACKGROUND: Symptomatic cerebral vasospasm following posterior fossa extraaxial tumor resection is a rare phenomenon, with only 13 cases previously reported in the literature. The condition appears similar to vasospasm following supratentorial tumor resection, intraaxial posterior fossa tumor resection, and aneurysmal subarachnoid hemorrhage (aSAH). The majority of patients were not evaluated for vasospasm prior to symptom onset, leading to a delay in diagnosis. OBSERVATIONS: The authors present their experience in a 56-year-old female who developed delayed cerebral vasospasm after excision of a solid-cystic vestibular schwannoma. Routine postoperative brain computed tomography showed evidence of subarachnoid hemorrhage in the basal cisterns. She was discharged on the 9th postoperative day. On the 11th day after tumor excision, she developed left hemiparesis, dysarthria, and dysphagia and was readmitted. Angiography confirmed bilateral diffuse cerebral vasospasm. The patient responded to standard hyperdynamic therapy used for vasospasm secondary to aSAH. LESSONS: Symptomatic distant cerebral vasospasm after posterior fossa extraaxial tumor excision is a rare but challenging complication with a very high morbidity rate in reported cases. A high index of suspicion is required for early diagnosis and prompt management for a favorable outcome.