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Handbook of Clinical Neurology 2021The worldwide incidence of spontaneous subarachnoid hemorrhage is about 6.1 per 100,000 cases per year (Etminan et al., 2019). Eighty-five percent of cases are due to... (Review)
Review
The worldwide incidence of spontaneous subarachnoid hemorrhage is about 6.1 per 100,000 cases per year (Etminan et al., 2019). Eighty-five percent of cases are due to intracranial aneurysms. The mean age of those affected is 55 years, and two-thirds of the patients are female. The prognosis is related mainly to the neurologic condition after the subarachnoid hemorrhage and the age of the patient. Overall, 15% of patients die before reaching the hospital, another 20% die within 30 days, and overall 75% are dead or remain disabled. Case fatality has declined by 17% over the last 3 decades. Despite the improvement in outcome probably due to improved diagnosis, early aneurysm repair, administration of nimodipine, and advanced intensive care support, the outcome is not very good. Even among survivors, 75% have permanent cognitive deficits, mood disorders, fatigue, inability to return to work, and executive dysfunction and are often unable to return to their premorbid level of functioning. The key diagnostic test is computed tomography, and the treatments that are most strongly supported by scientific evidence are to undertake aneurysm repair in a timely fashion by endovascular coiling rather than neurosurgical clipping when feasible and to administer enteral nimodipine. The most common complications are aneurysm rebleeding, hydrocephalus, delayed cerebral ischemia, and medical complications (fever, anemia, and hyperglycemia). Management also probably is optimized by neurologic intensive care units and multidisciplinary teams.
Topics: Aneurysm, Ruptured; Female; Humans; Hydrocephalus; Intracranial Aneurysm; Middle Aged; Subarachnoid Hemorrhage; Treatment Outcome; Vasospasm, Intracranial
PubMed: 33272393
DOI: 10.1016/B978-0-444-64034-5.00009-2 -
Neuroimaging Clinics of North America May 2021Cerebral vasospasm (VS) and delayed cerebral ischemia (DCI) are important complications of aneurysmal subarachnoid hemorrhage (ASAH). Imaging approaches to VS monitoring... (Review)
Review
Cerebral vasospasm (VS) and delayed cerebral ischemia (DCI) are important complications of aneurysmal subarachnoid hemorrhage (ASAH). Imaging approaches to VS monitoring include noninvasive bedside assessment with transcranial Doppler ultrasonography, angiographic evaluation with digital subtraction angiography, and computed tomography (CT) angiography. DCI is a clinical diagnosis and is not fully explained by the presence of angiographic VS. CT perfusion has shown clinical utility and implications for future research in the evaluation of DCI in patients with ASAH. This review article discusses the common approaches to diagnosis and monitoring of VS and DCI, current treatment strategies, and future research directions.
Topics: Angiography, Digital Subtraction; Brain Ischemia; Humans; Subarachnoid Hemorrhage; Tomography, X-Ray Computed; Vasospasm, Intracranial
PubMed: 33902870
DOI: 10.1016/j.nic.2021.01.004 -
Neurocritical Care Aug 2021Cerebral vasospasm is a major contributor to disability and mortality after aneurysmal subarachnoid hemorrhage. Oxidation of cell-free hemoglobin plays an integral role...
BACKGROUND
Cerebral vasospasm is a major contributor to disability and mortality after aneurysmal subarachnoid hemorrhage. Oxidation of cell-free hemoglobin plays an integral role in neuroinflammation and is a suggested source of tissue injury after aneurysm rupture. This study sought to determine whether patients with subarachnoid hemorrhage and cerebral vasospasm were more likely to have been exposed to early hyperoxemia than those without vasospasm.
METHODS
This single-center retrospective cohort study included adult patients presenting with aneurysmal subarachnoid hemorrhage to Vanderbilt University Medical Center between January 2007 and December 2017. Patients with an ICD-9/10 diagnosis of aneurysmal subarachnoid hemorrhage were initially identified (N = 441) and subsequently excluded if they did not have intracranial imaging, arterial PaO values or died within 96 h post-rupture (N = 96). The final cohort was 345 subjects. The degree of hyperoxemia was defined by the highest PaO measured within 72 h after aneurysmal rupture. The primary outcome was development of cerebral vasospasm, which included asymptomatic vasospasm and delayed cerebral ischemia (DCI). Secondary outcomes were mortality and modified Rankin Scale.
RESULTS
Three hundred and forty five patients met inclusion criteria; 218 patients (63%) developed vasospasm. Of those that developed vasospasm, 85 were diagnosed with delayed cerebral ischemia (DCI, 39%). The average patient age of the cohort was 55 ± 13 years, and 68% were female. Ninety percent presented with Fisher grade 3 or 4 hemorrhage (N = 310), while 42% presented as Hunt-Hess grade 4 or 5 (N = 146). In univariable analysis, patients exposed to higher levels of PaO by quintile of exposure had a higher mortality rate and were more likely to develop vasospasm in a dose-dependent fashion (P = 0.015 and P = 0.019, respectively). There were no statistically significant predictors that differentiated asymptomatic vasospasm from DCI and no significant difference in maximum PaO between these two groups. In multivariable analysis, early hyperoxemia was independently associated with vasospasm (OR = 1.15 per 50 mmHg increase in PaO2 [1.03, 1.28]; P = 0.013), but not mortality (OR = 1.10 [0.97, 1.25]; P = 0.147) following subarachnoid hemorrhage.
CONCLUSIONS
Hyperoxemia within 72 h post-aneurysmal rupture is an independent predictor of cerebral vasospasm, but not mortality in subarachnoid hemorrhage. Hyperoxemia is a variable that can be readily controlled by adjusting the delivered FiO and may represent a modifiable risk factor for vasospasm.
Topics: Adult; Aneurysm, Ruptured; Brain Ischemia; Female; Humans; Infant, Newborn; Retrospective Studies; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 33150573
DOI: 10.1007/s12028-020-01136-6 -
Journal of the College of Physicians... Nov 2022Hyperthyroidism is associated with a number of heart diseases, and it may aggravate previous cardiac problems or cause new ones, such as hyperthyroid cardiopathy. Cases...
Hyperthyroidism is associated with a number of heart diseases, and it may aggravate previous cardiac problems or cause new ones, such as hyperthyroid cardiopathy. Cases of hyperthyroidism presenting with coronary vasospasm are rarely reported. Herein, we present a case of a 54-year male patient with recurrent left chest pain for 2 months. Coronary angiography showed no obvious coronary artery stenosis, and coronary vasospasm was suspected. After admission, the patient's thyroid function and TSH-receptor antibody (TRAb) were abnormal. However, there was no obvious palpitation, hyperhidrosis, or weight loss, and the diagnosis of Graves' disease was rendered, which seemed to be the cause of coronary vasospasm. The patient did not experience chest pain after treatment with methimazole. Patients with coronary vasospasm should be investigated for the possibility of hyperthyroidism. Key Words: Hyperthyroidism, Chest pain, Coronary angiography, Coronary vasospasm.
Topics: Humans; Male; Coronary Vasospasm; Hyperthyroidism; Methimazole; Graves Disease; Antithyroid Agents; Chest Pain
PubMed: 36377023
DOI: 10.29271/jcpsp.2022.11.1492 -
Journal of Neurosurgery Nov 2023Cerebral arterial vasospasm is a dreaded sequela of aneurysm rupture and can result in significant narrowing of the surrounding vasculature and subsequent cerebral...
OBJECTIVE
Cerebral arterial vasospasm is a dreaded sequela of aneurysm rupture and can result in significant narrowing of the surrounding vasculature and subsequent cerebral ischemia. Treatment interventions are associated with distinct side effect profiles, including the risk of thrombosis and worsened ischemia, which may be associated with increased mortality-especially in older adults. An improved understanding of the likelihood of vasospasm in elderly patients would enable clinicians and patients to better consider the risks and benefits of vasospasm prophylaxis in this vulnerable population. This retrospective chart review aimed to assess the relationship between age at onset and the incidence of cerebral vasospasm among patients treated at the University of North Carolina Medical Center with spontaneous aneurysmal subarachnoid hemorrhage (aSAH).
METHODS
Electronic health record data from the Epic Systems Corp. database, compiled by the Carolina Data Warehouse for Health, were analyzed for patients older than 18 years who were previously treated for an SAH secondary to aneurysm at the University of North Carolina Medical Center within the past 10 years, ranging from June 2011 through June 2021. Logistic regression was used to calculate odds ratios and to determine the association of age with the occurrence of vasospasm following aSAH.
RESULTS
Of the 386 cases analyzed, 149 patients (38.6%) were older than 65 years at the time of aSAH. A total of 192 of the 386 patients (49.7%) developed vasospasm within the first 3-21 days following aSAH. Among the patients who developed vasospasm, only 31 of 192 patients (16.1%) were older than 65 years at the time of aneurysm rupture. Odds ratio calculations revealed that older adults (> 65 years) were 8 times less likely to develop vasospasm compared to their younger counterparts (p < 0.0001; 95% CI 5.0-13.0).
CONCLUSIONS
This study found that older patients are less likely to develop cerebral vasospasm following aSAH than are younger individuals. Age-associated changes in arteriosclerosis, inflammatory responses, and CSF dynamics may mitigate vascular narrowing in response to aSAH. This finding suggests that the aSAH treatment and vasospasm prevention paradigms should be revised to minimize potentially unnecessary interventions and avoid adverse outcomes for older adults.
Topics: Humans; Aged; Subarachnoid Hemorrhage; Retrospective Studies; Vasospasm, Intracranial; Cerebral Infarction; Aneurysm, Ruptured
PubMed: 37119113
DOI: 10.3171/2023.3.JNS222720 -
Annals of Palliative Medicine Jan 2022The incidence of cerebral hemorrhage has rapidly increased over time, and vascular dysfunction has a significant influence on the pathogenesis and outcome of these...
BACKGROUND
The incidence of cerebral hemorrhage has rapidly increased over time, and vascular dysfunction has a significant influence on the pathogenesis and outcome of these patients. This is also the case for vasospasm in cerebral hemorrhage, but there is no method to assess this. We conducted this study to find molecular biomarkers of vasospasm in cerebral hemorrhage patients.
METHODS
Raw data of GSE37924 was downloaded from the Gene Expression Omnibus (GEO) database, including 66 samples with cerebral vasospasm and 62 samples without cerebral vasospasm. Differentially expressed genes (DEGs) between samples with cerebral vasospasm and those without cerebral vasospasm were analyzed using the limma package in R software. To determine the functions of DEGs, we conducted functional enrichment analysis of DEGs through the clusterProfiler package in R. The protein-protein interaction (PPI) network of DEGs was constructed through STRING (https://string-db.org/) and generated via Cytoscape software. To understand the correlation between DEGs and immune-related genes, immune-related cerebral vasospasm genes were obtained via intersecting immune-related genes and cerebral vasospasm DEGs. We also compared the infiltration of 28 immune cells between cases with cerebral vasospasm and those without cerebral vasospasm. Finally, we constructed a model to perform the validation experiments.
RESULTS
Of the DEGs, there were 24 upregulated and 21 downregulated genes in the vasospasm samples compared to the no-vasospasm samples. Functional enrichment analysis showed that these genes play key roles in several biological processes and signaling pathways such as the bone morphogenetic protein (BMP) signaling pathway, cellular response to BMP stimulus, natural killer cell chemotaxis, negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway, MHC protein complex binding, and receptor ligand activity, among others. CCL4, HLA-DQA1, IGF2, NTS, and so on were the significant immune-related genes. Furthermore, the immune cell infiltration results showed that there were differences between patients with vasospasm and those without vasospasm. Finally, we found that CCL4 had significantly higher expression in patients with vasospasm than those without vasospasm.
CONCLUSIONS
CCL4 is an important regulator of vascular dysfunction in cerebral hemorrhage.
Topics: Biomarkers; Cerebral Hemorrhage; Computational Biology; Gene Expression Profiling; Humans; Protein Interaction Maps
PubMed: 35144409
DOI: 10.21037/apm-21-3717 -
Journal of Cerebrovascular and... Jun 2021Cerebral vasospasm is a significant cause of morbidity and mortality associated with aneurysmal subarachnoid hemorrhage (aSAH). Intra-arterial chemical and mechanical...
Cerebral vasospasm is a significant cause of morbidity and mortality associated with aneurysmal subarachnoid hemorrhage (aSAH). Intra-arterial chemical and mechanical angioplasty, performed alone or in combination, have been shown to ameliorate cerebral vasospasm and improve patient outcomes. Few options exist for patients who fail these traditional endovascular tactics. We propose a hybrid microcatheter technique that combines the mechanical benefit of transient high pressure induced by microcatheter fluid bolus with a low-dose vasodilator infusion. Five patients with moderate to severe symptomatic vasospasm who failed medical and traditional endovascular management were treated using a hybrid microcatheter technique. All angioplasty procedures were technically successful, and the degree of vasospasm improved following angioplasty. There were no complications related to the cerebral angioplasty procedures. None of the patients required repeat endovascular intervention. Hybrid microcatheter angioplasty may be a useful complement to mechanical or pharmacological techniques in the endovascular management of intractable cerebral vasospasm after aSAH.
PubMed: 34038994
DOI: 10.7461/jcen.2021.E2020.11.001 -
Journal of Clinical Medicine Aug 2022Vasospasm after the rupture of an intracranial aneurysm is a frequent phenomenon and is the main cause of morbidity and mortality in patients who have survived...
BACKGROUND
Vasospasm after the rupture of an intracranial aneurysm is a frequent phenomenon and is the main cause of morbidity and mortality in patients who have survived intracranial hemorrhage and aneurysm treatment. We analyzed the diagnosis and management of patients with aneurysmal subarachnoid hemorrhage who eventually died from ischemic brain damage due to vasospasm.
METHODS
Between January 2007 and December 2021 (15 years), a total of 1064 patients were diagnosed with an aneurysmal intracranial hemorrhage in a single comprehensive neurovascular center. Vasospasm was diagnosed in 408 patients (38.4%). A total of 187 patients (17.6%) died within 90 days of the aneurysm rupture. In 64 of these 187 patients (33.7%), vasospasm was considered to be the cause of death. In a retrospective analysis, demographic and clinical data for patients without, with non-fatal, and with fatal vasospasm were compared. The patients with fatal vasospasm were categorized into the following subgroups: "no diagnosis and treatment" (Group a), "delayed diagnosis" (Group b), "cardiovascular complications" (Group c), and "vasospasm-treatment complications" (Group d).
RESULTS
Among the patients with fatal vasospasm, 31 (48.4%) were assigned to group a, 26 (40.6%) to group b, seven (10.9%) to group c, and none (0%) to group d.
CONCLUSION
The early recognition of severe posthemorrhagic vasospasm is a prerequisite for any treatment and requires routine diagnostic imaging in all unconscious patients. Aggressive endovascular vasospasm treatment may fail to prevent death but is infrequently the cause of a fatal outcome.
PubMed: 36012881
DOI: 10.3390/jcm11164642 -
Neurosurgery Mar 2021Cerebral vasospasm is a major source of morbidity and mortality following aneurysm rupture and has limited treatment options.
BACKGROUND
Cerebral vasospasm is a major source of morbidity and mortality following aneurysm rupture and has limited treatment options.
OBJECTIVE
To evaluate the role of programmed death-1 (PD-1) in cerebral vasospasm.
METHODS
Endovascular internal carotid artery perforation (ICAp) was used to induce cerebral vasospasm in mice. To evaluate the therapeutic potential of targeting PD-1, programmed death ligand-1 (PD-L1) was administered 1 h after ICAp and vasospasm was measured histologically at the level of the ICA bifurcation bilaterally. PD-1 expressing immune cell populations were evaluated by flow cytometry. To correlate these findings to patients and evaluate the potential of PD-1 as a biomarker, monocytes were isolated from the peripheral blood and analyzed by flow cytometry in a cohort of patients with ruptured cerebral aneurysms. The daily frequency of PD-1+ monocytes in the peripheral blood was correlated to transcranial Doppler velocities as well as clinical and radiographic vasospasm.
RESULTS
We found that PD-L1 administration prevented cerebral vasospasm by inhibiting ingress of activated Ly6c+ and CCR2+ monocytes into the brain. Human correlative studies confirmed the presence of PD-1+ monocytes in the peripheral blood of patients with ruptured aneurysms and the frequency of these cells corresponded with cerebral blood flow velocities and clinical vasospasm.
CONCLUSION
Our results identify PD-1+ monocytes as mediators of cerebral vasospasm and support PD-1 agonism as a novel therapeutic strategy.
Topics: Animals; Brain; Cerebrovascular Circulation; Cohort Studies; Mice; Mice, Inbred C57BL; Monocytes; Programmed Cell Death 1 Receptor; Subarachnoid Hemorrhage; Ultrasonography, Doppler, Transcranial; Vasospasm, Intracranial
PubMed: 33370819
DOI: 10.1093/neuros/nyaa495 -
Neurocritical Care Jun 2022Angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is associated with delayed cerebral ischemia (DCI)-related cerebral infarction (radiological DCI)...
BACKGROUND
Angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is associated with delayed cerebral ischemia (DCI)-related cerebral infarction (radiological DCI) and worsened neurological outcome. Transcranial Doppler (TCD) measurements of cerebral blood flow velocity are commonly used after aSAH to screen for vasospasm; however, their association with cerebral infarction is not well characterized. We sought to determine whether time-varying TCD-measured vasospasm severity is associated with cerebral infarction and investigate the performance characteristics of different time/severity cutoffs for predicting cerebral infarction.
METHODS
We conducted a retrospective single-center cohort study of consecutive adult patients with aSAH with at least one TCD study between 2011 and 2020. The primary outcome was radiological DCI, defined as a cerebral infarction developing at least 2 days after any surgical or endovascular intervention without an alternative cause. Cox proportional hazards models were used to examine associations between time-varying vasospasm severity and radiological DCI. Optimal TCD-based time/severity thresholds for predicting radiological DCI were then determined.
RESULTS
Of 262 patients with aSAH who underwent TCD studies, 27 (10%) developed radiological DCI. Patients with radiological DCI had higher modified Fisher scale scores and trended toward earlier onset of vasospasm. Adjusted for age, Hunt and Hess scores, and modified Fisher scale scores, the worst-vessel vasospasm severity was associated with radiological DCI (adjusted hazard ratio 1.7 [95% confidence interval 1.1-2.4]). Vasospasm severity within a specific vessel was associated with risk of delayed infarction in the territory supplied by that vessel. Optimal discrimination of patients with radiological DCI was achieved with thresholds of mild vasospasm on days 4-5 or moderate vasospasm on days 6-9, with negative predictive values greater than 90% and positive predictive values near 20%.
CONCLUSIONS
TCD-measured vasospasm severity is associated with radiological DCI after aSAH. An early, mild TCD-based vasospasm severity threshold had a high negative predictive value, supporting its role as a screening tool to identify at-risk patients.
Topics: Adult; Autonomic Nervous System Diseases; Brain Ischemia; Cerebral Infarction; Cohort Studies; Humans; Retrospective Studies; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 34751900
DOI: 10.1007/s12028-021-01382-2