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European Journal of Pharmacology Jun 2024Subarachnoid hemorrhage (SAH) is a neurological condition with high mortality and poor prognosis, and there are currently no effective therapeutic drugs available. Poly...
Subarachnoid hemorrhage (SAH) is a neurological condition with high mortality and poor prognosis, and there are currently no effective therapeutic drugs available. Poly (ADP-ribose) polymerase 1 (PARP-1) dependent cell death pathway-parthanatos is closely associated with stroke. We investigated improvements in neurological function, oxidative stress, blood-brain barrier and parthanatos-related protein expression in rats with SAH after intraperitoneal administration of PARP-1 inhibitor (AG14361). Our study found that the expression of parthanatos-related proteins was significantly increased after SAH. Immunofluorescence staining showed increased expression of apoptosis-inducing factor (AIF) in the nucleus after SAH. Administration of PARP-1 inhibitor significantly reduced malondialdehyde (MDA) level and the expression of parthanatos-related proteins. Immunofluorescence staining showed that PARP-1 inhibitor reduced the expression of 8-hydroxy-2' -deoxyguanosine (8-OHdG) and thus reduced oxidative stress. Moreover, PARP-1 inhibitor could inhibit inflammation-associated proteins level and neuronal apoptosis, protect the blood-brain barrier and significantly improve neurological function after SAH. These results suggest that PARP-1 inhibitor can significantly improve SAH, and the underlying mechanism may be through inhibiting parthanatos pathway.
PubMed: 38906236
DOI: 10.1016/j.ejphar.2024.176765 -
Neurosurgical Review Jun 2024Delayed cerebral ischemia is a major neurological complication of aneurysmal subarachnoid hemorrhage. Its unpredictable course and potentially unfavorable outcome draw...
Delayed cerebral ischemia is a major neurological complication of aneurysmal subarachnoid hemorrhage. Its unpredictable course and potentially unfavorable outcome draw attention to clinicians to improve the methods for its prediction, prevention, and diagnosis. The computed tomography perfusion (CTP) technique of the brain is one of the promising methods for revealing brain areas endangered by cerebral vasospasm and delayed cerebral ischemia.
Topics: Humans; Brain Ischemia; Subarachnoid Hemorrhage; Tomography, X-Ray Computed; Vasospasm, Intracranial
PubMed: 38904832
DOI: 10.1007/s10143-024-02525-7 -
Frontiers in Neurology 2024Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid...
INTRODUCTION
Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid hemorrhage (SAH) in the Japanese population, as demonstrated by a recent randomized phase 3 trial. However, evidence to suggest clazosentan should be prioritized over the current standard of care to prevent cerebral vasospasm is still lacking. Therefore, we investigated the efficacy and safety of clazosentan in comparison with conventional postoperative management in real-world clinical practice.
METHODS
We conducted a single-center, retrospective, observational cohort study using prospectively collected data from consecutive patients with aneurysmal SAH. After clazosentan was approved for use in Japan, the conventional postoperative management protocol, composed of intravenous fasudil chloride and oral cilostazol (control group, April 2021 to March 2022), was changed to the clazosentan protocol (clazosentan group, April 2022 to March 2023). The primary endpoint was the incidence of vasospasm-related symptomatic infarction. The secondary endpoints were favorable functional outcomes (modified Rankin scale score < 3) at discharge, angiographic vasospasm, and the need for rescue therapy for delayed cerebral ischemia.
RESULTS
The analysis included 100 and 81 patients in the control and clazosentan groups, respectively. The incidence of vasospasm-related symptomatic infarction was significantly lower in the clazosentan group than in the control group (6.2% vs. 16%, = 0.032). Multiple logistic analyses demonstrated that the use of clazosentan was independently associated with fewer incidence of vasospasm-related symptomatic infarct (23.8% vs. 47.5%, odds ratio 0.34 [0.12-0.97], = 0.032). Clazosentan was significantly associated with favorable outcomes at discharge (79% vs. 66%, = 0.037). Moreover, both the incidence of angiographic vasospasm (25.9% vs. 44%, = 0.013) and the need for rescue therapy (16.1% vs. 34%, = 0.006) was lower in the clazosentan group. The occurrence of pulmonary edema was significantly higher with clazosentan use (19.8% vs. 5%, = 0.002), which did not result in morbidity.
CONCLUSION
A postoperative management protocol centering on clazosentan was associated with the reduced vasospasm-related symptomatic infarction and improved clinical outcomes compared to the conventional management protocol in Japanese clinical practice. Clazosentan might be a promising treatment option for counteracting cerebral vasospasm after aneurysmal SAH.
PubMed: 38903164
DOI: 10.3389/fneur.2024.1413632 -
Neurocritical Care Jun 2024
PubMed: 38902583
DOI: 10.1007/s12028-024-02034-x -
Neurocritical Care Jun 2024
PubMed: 38902582
DOI: 10.1007/s12028-024-02032-z -
Neurocritical Care Jun 2024Temperature abnormalities are common after spontaneous subarachnoid hemorrhage (SAH). Here, we aimed to describe the evolution of temperature burden despite temperature...
BACKGROUND
Temperature abnormalities are common after spontaneous subarachnoid hemorrhage (SAH). Here, we aimed to describe the evolution of temperature burden despite temperature control and to assess its impact on outcome parameters.
METHODS
This retrospective observational study of prospectively collected data included 375 consecutive patients with SAH admitted to the neurological intensive care unit between 2010 and 2022. Daily fever (defined as the area over the curve above 37.9 °C multiplied by hours with fever) and spontaneous hypothermia burden (< 36.0 °C) were calculated over the study period of 16 days. Generalized estimating equations were used to calculate risk factors for increased temperature burdens and the impact of temperature burden on outcome parameters after correction for predefined variables.
RESULTS
Patients had a median age of 58 years (interquartile range 49-68) and presented with a median Hunt & Hess score of 3 (interquartile range 2-5) on admission. Fever (temperature > 37.9 °C) was diagnosed in 283 of 375 (76%) patients during 14% of the monitored time. The average daily fever burden peaked between days 5 and 10 after admission. Higher Hunt & Hess score (p = 0.014), older age (p = 0.033), and pneumonia (p = 0.022) were independent factors associated with delayed fever burden between days 5 and 10. Increased fever burden was independently associated with poor 3-month functional outcome (modified Rankin Scale 3-6, p = 0.027), poor 12-month functional outcome (p = 0.020), and in-hospital mortality (p = 0.045), but not with the development of delayed cerebral ischemia (p = 0.660) or intensive care unit length of stay (p = 0.573). Spontaneous hypothermia was evident in the first three days in patients with a higher Hunt & Hess score (p < 0.001) and intraventricular hemorrhage (p = 0.047). Spontaneous hypothermia burden was not associated with poor 3-month outcome (p = 0.271).
CONCLUSIONS
Early hypothermia was followed by fever after SAH. Increased fever time burden was associated with poor functional outcome after SAH and could be considered for neuroprognostication.
PubMed: 38902581
DOI: 10.1007/s12028-024-02022-1 -
[Epidemiological characteristics of spontaneous subarachnoid hemorrhage cases in Shandong province].Zhonghua Yi Xue Za Zhi Jun 2024To investigate the characteristics and trends of spontaneous subarachnoid hemorrhage (SAH) in Shandong province. In this study, SAH incidence data of residents from...
To investigate the characteristics and trends of spontaneous subarachnoid hemorrhage (SAH) in Shandong province. In this study, SAH incidence data of residents from 2012 to 2021 were collected from the chronic disease monitoring information management system of Shandong province, including the basic information of outpatient, emergency or inpatient cases and out-of-hospital deaths (name, gender, ID number, address, etc.) and disease diagnosis information (disease diagnosis, date of onset, date of diagnosis, etc.). The crude incidence rate and age-standardized incidence rate were used as indicators to describe the incidence of SAH in different gender, age groups and regions (urban and rural areas). Joinpoint regression was used to analyze the variation of incidence rate and age by year. The rate difference decomposition method was used to estimate the contribution of population aging to the increase of SAH incidence. Global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software. From 2012 to 2021, a total of 11 629 cases of SAH were reported from 19 provincial monitoring sites in Shandong province. Among them, 54.11% (6 293 cases) were female and 91.87% (10 684 cases) were≥45 years old. The reported crude incidence rate increased from 5.26/100 000 to 9.50/100 000, with an average annual increase of 7.75% (=7.30, <0.001), and the standardized incidence rate also showed an upward trend (=3.92, =0.004). The crude incidence rate of women was higher than that of men in all years (all values<0.05), and the standardized incidence rate of women was higher than that of men in all years except in 2012 and 2021 (all values<0.05). In 2012, the crude incidence and standardized incidence of urban residents were lower than those in rural areas (<0.05); from 2013 to 2017, the urban incidence was higher than that in rural areas; and after 2018, the rural incidence exceeded the urban incidence again (all values<0.05). The median age of onset of SAH increased from 61.9 years in 2012 to 67.2 years in 2021. The age of onset of SAH in men was lower than that in women in all years (all <0.05), and there was no significant difference between urban and rural residents in most years (>0.05). The incidence of SAH increased with age (<0.001), with a low incidence reported in residents aged<45 years and a rapid increase in residents aged≥45 years. According to the seasonal decomposition, the incidence of SAH had three small peaks in January, March to May and October to November. From 2013 to 2021, the contribution of aging population to the increase of crude incidence of SAH increased from 27.86% to 43.68%. The global spatial autocorrelation analysis showed that the incidence of SAH was in an obvious spatial aggregation distribution (Moran's >0, <0.05). Local spatial autocorrelation analysis showed that the counties with high incidence were mainly concentrated in Dezhou City in northwest Shandong Province and Heze city in southwest Shandong province. The crude incidence rate of SAH in Shandong province is increasing, with spatial clustering and seasonal clustering. Residents aged 45 years and older, female residents, and rural residents are at high risk of developing SAH, so targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustered areas.
Topics: Humans; Subarachnoid Hemorrhage; China; Incidence; Female; Male; Rural Population; Prevalence; Middle Aged; Urban Population; Adult; Aged
PubMed: 38901982
DOI: 10.3760/cma.j.cn112137-20240218-00324 -
World Neurosurgery Jun 2024A 54-year-old woman, with no medical history presented with severe headache, nauseas and vomiting for 8 days. Imaging exams revealed subarachnoid hemorrhage in the left...
A 54-year-old woman, with no medical history presented with severe headache, nauseas and vomiting for 8 days. Imaging exams revealed subarachnoid hemorrhage in the left interpeduncular cistern, without aneurysms. Computed tomography angiography and digital subtraction angiography found an anomalous vein near the site of the hemorrhagic clots, indicating abnormalities in cerebral venous drainage that provided an anastomosis between the drainage system of the deep middle cerebral, petrosal, and lateral mesencephalic veins. In the primitive pattern, the basal vein of Rosenthal drains into the lateral mesencephalic vein and to the petrosal sinus. This anomalous flow may predispose to subarachnoid hemorrhage, emphasizing the association between non-aneurysmal perimesencephalic hemorrhage and venous anomalies.
PubMed: 38901479
DOI: 10.1016/j.wneu.2024.06.070 -
EBioMedicine Jun 2024Cerebral 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...
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.
PubMed: 38901147
DOI: 10.1016/j.ebiom.2024.105206 -
Neurology Jul 2024Cerebral amyloid angiopathy-related inflammation (CAA-RI) and biopsy-positive primary angiitis of the CNS (BP-PACNS) have overlapping clinicoradiologic presentations. It... (Comparative Study)
Comparative Study
BACKGROUND AND OBJECTIVES
Cerebral amyloid angiopathy-related inflammation (CAA-RI) and biopsy-positive primary angiitis of the CNS (BP-PACNS) have overlapping clinicoradiologic presentations. It is unknown whether clinical and radiologic features can differentiate CAA-RI from BP-PACNS and whether both diseases have different relapse rates. The objectives of this study were to compare clinicoradiologic presentations and relapse rates in patients with CAA-RI vs BP-PACNS.
METHODS
Patients with CAA-RI and BP-PACNS were enrolled from 2 retrospective multicenter cohorts. Patients with CAA-RI were biopsy-positive or met probable clinicoradiologic criteria. Patients with BP-PACNS had histopathologic confirmation of CNS angiitis, with no secondary etiology. A neuroradiologist read brain MRIs, blinded to the diagnosis of CAA-RI or BP-PACNS. Clinicoradiologic features were compared using univariable logistic regression models. Relapse rates were compared using a univariable Fine-Gray subdistribution hazard model, with death as a competing risk.
RESULTS
This study enrolled 104 patients with CAA-RI (mean age 73 years, 48% female sex) and 52 patients with BP-PACNS (mean age 45 years, 48% female sex). Patients with CAA-RI more often had white matter hyperintense lesions meeting the probable CAA-RI criteria (93% vs 51%, < 0.001), acute subarachnoid hemorrhage (15% vs 2%, = 0.02), cortical superficial siderosis (27% vs 4%, < 0.001), ≥1 lobar microbleed (94% vs 26%, < 0.001), past intracerebral hemorrhage (17% vs 4%, = 0.04), ≥21 visible centrum semiovale perivascular spaces (34% vs 4%, < 0.01), and leptomeningeal enhancement (70% vs 27%, < 0.001). Patients with BP-PACNS more often had headaches (56% vs 31%, < 0.01), motor deficits (56% vs 36%, = 0.02), and nonischemic parenchymal gadolinium enhancement (82% vs 16%, < 0.001). The prevalence of acute ischemic lesions was 18% in CAA-RI and 22% in BP-PACNS ( = 0.57). The features with the highest specificity for CAA-RI were acute subarachnoid hemorrhage (98%), cortical superficial siderosis (96%), past intracerebral hemorrhage (96%), and ≥21 visible centrum semiovale perivascular spaces (96%). The probable CAA-RI criteria had a 71% sensitivity (95% CI 44%-90%) and 91% specificity (95% CI 79%-98%) in differentiating biopsy-positive CAA-RI from BP-PACNS. The rate of relapse in the first 2 years after remission was lower in CAA-RI than in BP-PACNS (hazard ratio 0.46, 95% CI 0.22-0.96, = 0.04).
CONCLUSION
Clinicoradiologic features differed between patients with CAA-RI and those with BP-PACNS. Specific markers for CAA-RI were hemorrhagic signs of subarachnoid involvement, past intracerebral hemorrhage, ≥21 visible centrum semiovale perivascular spaces, and the probable CAA-RI criteria. A biopsy remains necessary for diagnosis in some cases of CAA-RI. The rate of relapse in the first 2 years after disease remission was lower in CAA-RI than in BP-PACNS.
Topics: Humans; Female; Male; Cerebral Amyloid Angiopathy; Aged; Middle Aged; Vasculitis, Central Nervous System; Retrospective Studies; Biopsy; Magnetic Resonance Imaging; Aged, 80 and over; Brain; Adult; Recurrence
PubMed: 38900992
DOI: 10.1212/WNL.0000000000209548