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Research Square Jun 2024Background and Purpose Impaired cerebral circulation, induced by blood vessel constrictions and microthrombi, leads to delayed cerebral ischemia after subarachnoid...
Background and Purpose Impaired cerebral circulation, induced by blood vessel constrictions and microthrombi, leads to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). 12/15-Lipooxygenase (12/15-LOX) overexpression has been implicated in worsening early brain injury outcomes following SAH. However, it is unknown if 12/15-LOX is important in delayed pathophysiological events after SAH. Since 12/15-LOX produces metabolites that induce inflammation and vasoconstriction, we hypothesized that 12/15-LOX leads to microvessel constriction and microthrombi formation after SAH, and thus 12/15-LOX is an important target to prevent delayed cerebral ischemia. Methods SAH was induced in C57BL/6 and 12/15-LOX mice of both sexes by endovascular perforation. Expression of 12/15-LOX was assessed in brain tissue slices and . C57BL/6 mice were administered either ML351 (12/15-LOX inhibitor) or vehicle. Mice were evaluated for daily neuroscore and euthanized on day five to assess cerebral 12/15-LOX expression, vessel constrictions, platelet activation, microthrombi, neurodegeneration, infarction, cortical perfusion, and for development of delayed deficits. Finally, the effect of 12/15-LOX inhibition on platelet activation was assessed in SAH patient samples using a platelet spreading assay. Results In SAH mice, 12/15-LOX was upregulated in brain vascular cells and there was an increase in 12-S-HETE. Inhibition of 12/15-LOX improved brain perfusion on days 4-5 and attenuated delayed pathophysiological events, including microvessel constrictions, microthrombi, neuronal degeneration, and infarction. Additionally, 12/15-LOX inhibition reduced platelet activation in human and mouse blood samples. Conclusions Cerebrovascular 12/15-LOX overexpression plays a major role in brain dysfunction after SAH by triggering microvessel constrictions and microthrombi formation, which reduces brain perfusion. Inhibiting 12/15-LOX may be a therapeutic target to improve outcomes after SAH.
PubMed: 38947083
DOI: 10.21203/rs.3.rs-4468292/v1 -
Neurocirugia (English Edition) Jun 2024In Europe, units with Dual-trained Neurovascular Surgeons (DTNS) skilled in both open neurosurgery (ON) and endovascular neurosurgery (EN) are scarce. For instance, in...
OBJETIVE
In Europe, units with Dual-trained Neurovascular Surgeons (DTNS) skilled in both open neurosurgery (ON) and endovascular neurosurgery (EN) are scarce. For instance, in Spain, our unit is unique within the public health system, where all neurovascular procedures are carried out by DTNS. Our study aims to evaluate the evolution in treating ruptured intracranial aneurysms (rICAs) and assess the impact of this evolution on clinical outcomes.
METHODS
A retrospective cohort study was performed on rICAs treated in our unit from October 2012 to June 2023. We reviewed clinical and radiological data to analyze the evolution of ON and EN over time, as well as their impact on patient outcomes. Univariate, multivariate, and mixed-effects models were utilized to discern temporal changes.
RESULTS
The modified Fisher Scale (mFS) and the modified World Federation of Neurological Surgeons scale (mWFNS) showed strong correlation with the outcome at 6 months outcomes, both with p < 0.00001. However, the surgical intervention method, ON versus EN, did not significantly affect outcomes (p > 0.85). In adjusted multivariate logistic regression, mFS (-1.579, p: 0.011) and mWFNS (-0.872, p < 0.001) maintained their significance. rICAs location was significant when comparing ON to EN p = 0.0001. A significant temporal trend favored the selection of EN p = 0.0058). Mixed-effects time series modeling indicated that while patient characteristics and rICA specifics did not predict treatment choice, the year of treatment was significantly correlated (0.161, p = 0.002). Logistic regression with interaction terms for time and treatment type did not produce significant results.
CONCLUSION
Our findings suggest that despite an increased adoption of EN techniques, there has been no change in patient outcomes. Even with the rise of EN, our unit continues to perform ON for a higher proportion of rICAs than most national hospitals. We propose that a "dual approach" offers advantages in a patient individualized treatment decision protocol in the European context.
PubMed: 38945298
DOI: 10.1016/j.neucie.2024.06.003 -
Mymensingh Medical Journal : MMJ Jul 2024A young boy presented with features of non-traumatic Subarachnoid hemorrhage (SAH) with hematemesis and melaena. He has had past history of prolonged bleeding following...
A young boy presented with features of non-traumatic Subarachnoid hemorrhage (SAH) with hematemesis and melaena. He has had past history of prolonged bleeding following cut injury even requiring blood transfusion after circumcision. On examination, he was found confused, severely anemic, with presence of neck rigidity and painful swelling of right knee joint. But no positive family history was found. Non-contrast CT scan showed SAH. Cerebral angiography showed no aneurysm but knee joint had features of hemarthrosis. He was resuscitated and hemophilia was diagnosed on the basis of clinical suspicion of clotting factor assay. Specific treatment started in collaboration with Department of Hematology. This is a rare presentation of hemophilia as well as very uncommon cause of non-traumatic non-aneurysmal SAH.
Topics: Humans; Hemophilia A; Male; Subarachnoid Hemorrhage; Adolescent
PubMed: 38944742
DOI: No ID Found -
Neurocirugia (English Edition) Jun 2024Chiari malformations (CM) are often diagnosed in childhood and younger adults, with an incidence of only 0.77% in adult populations. Patients with CM may develop...
Chiari malformations (CM) are often diagnosed in childhood and younger adults, with an incidence of only 0.77% in adult populations. Patients with CM may develop syringomyelia and increased intracranial pressure (ICP) due to cerebrospinal fluid (CSF) obstruction and altered fluid dynamics at the cervicomedullary junction. We describe the case of a 65-year-old female presenting with an angionegative subarachnoid hemorrhage (SAH) with concomitant new diagnosis of CM type I with syringomyelia. After ruling out any aneurysm or vascular malformations, she underwent a suboccipital craniectomy for a Chiari decompression with a C1 laminectomy. There were no complications with the surgery and her symptoms improved. This case report highlights the unusual presentation of a CM. A menudo, las malformaciones de Chiari (CM) son diagnosticadas en los niños y los adultos jóvenes, y la incidencia en la populación adulto es solamente 0.77%. A veces, los pacientes con CM desarrollan una siringomielia y la hipertensión intracraneal debido a la obstrucción del líquido cefalorraquídeo y los cambios a los dinámicos del fluido a la unión craneocervical. Nosotros describimos el caso de una mujer de 65-años que presentó con una hemorragia subaracnoideo, que no apareció en el angiograma, y con un nuevo diagnóstico de CM 1 con una siringomielia. Después de nosotros excluimos cualquier aneurisma o malformación vascular, hicimos una craneotomía suboccipital para una descompresión de Chiari con una laminectomía de C1. No fue otras complicaciones con la cirugía y sus síntomas mejoraron. Este caso clínico recalca una presentación anormal de una CM.
PubMed: 38944205
DOI: 10.1016/j.neucie.2024.06.002 -
Journal of Neurosurgery Jun 2024The aim of this study was to evaluate the morbidity associated with microsurgical treatment in patients with a recurrent aneurysm to improve their surgical management.
OBJECTIVE
The aim of this study was to evaluate the morbidity associated with microsurgical treatment in patients with a recurrent aneurysm to improve their surgical management.
METHODS
From 2012 to 2022, among the 3128 patients with ruptured or unruptured intracranial aneurysms managed at the authors' institution, 954 patients were treated by a microsurgical procedure. Of these 3128 patients, 60 consecutive patients (6.3%) who had a recurrent microsurgically treated aneurysm after previous endovascular treatment were included in this study. Additional microsurgical treatment was considered in case of progressive remnant growth or significant aneurysm recurrence. Intraoperative and postoperative complications were noted. Early (< 7 days) and long-term clinical and radiological monitoring were performed. Good functional outcome was considered as a modified Rankin Scale score < 3.
RESULTS
The mean age at initial treatment was 45 years (range 26-65 years). The mean delay between the first treatment and microsurgical treatment of the recurrence was 64 months (range 2 days-296 months). The mean size of the fundus recurrence was 5 mm, and the mean size of the neck recurrence was 4.6 mm. Five patients (8.3%) presented with subarachnoid hemorrhage associated with rupture of the recurrent aneurysm. Three patients died (6%) of aneurysm rupture and/or intensive care complications. The total morbidity rate associated with the microsurgical procedure was 14.5% (8/55) in patients with unruptured recurrent aneurysms. Among these patients, postoperative definitive complications (ischemic lesions) directly related to the microsurgical procedure were present in 3 patients (5.5%). Intraoperative rupture was recorded in these 3 patients. In the 54 surviving patients with unruptured recurrent aneurysms, good functional outcome was noted in 49 (91%). Poor functional outcome was significantly associated with intraoperative rupture.
CONCLUSIONS
Microsurgery remains an effective therapeutic option for recurrent intracranial aneurysms. However, in the authors' experience, postoperative morbidity is higher than in patients with nonrecurrent aneurysms. Therefore, a pretherapeutic multidisciplinary evaluation is mandatory to reduce the potential morbidity associated with the retreatment as much as possible. When endovascular occlusion of the aneurysm requires both stenting and coiling, alternative microsurgical treatment should be carefully evaluated, as microsurgical clipping will become much more challenging in cases of aneurysm recurrence.
PubMed: 38941640
DOI: 10.3171/2024.3.JNS24116 -
Alternative Therapies in Health and... Jun 2024Cerebral aneurysm can rupture a blood vessel and cause bleeding in the brain. Microsurgical clipping of the tumor neck has been reported to be effective in treating...
Clinical Efficacy of Early Microsurgical Clipping of Tumor Neck in the Treatment of Cerebral Aneurysm Rupture and Bleeding and Its Impact on Oxidative Stress Response and Prognosis of Patients.
BACKGROUND
Cerebral aneurysm can rupture a blood vessel and cause bleeding in the brain. Microsurgical clipping of the tumor neck has been reported to be effective in treating cerebral aneurysm rupture and bleeding.
OBJECTIVE
This research attempted to clarify the clinical efficacy of early microsurgical clipping of tumor neck for treating cerebral aneurysm rupture and bleeding, and its impact on prognosis of patients.
DESIGN
This was a retrospective study.
SETTING
This study was carried out in the Department of Neurosurgery, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third People's Hospital.
UNLABELLED
One hundred patients with cerebral aneurysm rupture and bleeding patients aged from 23 to 70 years old, and diagnosed with CA rupture and bleeding through imaging examinations such as CT angiography (CTA) and digital subtraction angiography (DSA), and there was spontaneous subarachnoid hemorrhage treated in our hospital from November 2020 to November 2022 were selected and divided into an experimental group (n=25) and a control group (n=25) according to surgical time.
INTERVENTIONS
All patients underwent microsurgical clipping of the tumor neck for therapy. Under microscope monitoring, the temporal and frontal lobes of the patient were separated, and the tumor body was selected in the internal carotid artery and cerebral artery. After the tumor neck of the patient was exposed, the artery supplying blood was clipped and appropriate tumor clips were selected. The control group chose to undergo surgery 72 h after the onset of cerebral aneurysm rupture and bleeding, while the experimental group chose to undergo complete surgery within 72 h after the onset of cerebral aneurysm rupture and bleeding. After surgery, targeted treatment were given to patients in 2 groups based on their physical condition, such as dehydration to reduce intracranial pressure, anti-vasospasm, anti-infection, monitoring of neurological changes, and monitoring of vital signs. Cerebral angiography should also be performed for reexamination.
PRIMARY OUTCOME MEASURES
(1) incidence of complications (2) cognitive function scores assessed by Montreal Cognitive Assessment (MoCA) (3) prognosis assessed by Glasgow Outcome Scale (GOS) (4) surgical indicators (5) oxidative stress response and (6) quality of life assessed by short form 36 health survey questionnaire (SF-36).
RESULTS
Compared to the control group, the incidence of complications in the experimental group exhibited depletion (24.0% vs 8.0%) (P < .05), the prognosis in the experimental group exhibited elevation [(2.23±0.45) points vs (4.12±0.3) points] (P < .05), the hospitalization time in the experimental group exhibited depletion [(15.69±1.21) d vs (11.31±0.65) d] (P < .05), the nomination, abstraction, language, orientation, attention, delayed recall and visual and executive function scores and total scores in experimental group exhibited elevation [(2.69±0.52 points, 2.07±0.63 points, 3.02±0.44 points, 2.45±0.51 points, 3.12±0.36 points, 2.14±0.75 points, 3.15±0.64 points and 17.24±2.15 points) vs (4.25±0.65 points, 3.88±1.08 points, 5.03±0.73 points, 3.34±0.72 points, 4.05±0.66 points, 3.85±0.33 points, 5.02±1.04 points and 26.89±1.33 points)] (P < .05), serum levels of oxidative stress-related indicators in the experimental group exhibited depletion [(462.14±48.47 ng/mL, 281.14±36.44 ng/mL and 1.62±0.12 nmol/mL) vs (365.58±44.56 ng/mL, 201.51±34.47 ng/mL and 1.15±0.1 nmol/mL)](P < .05) and the quality of life in experimental group exhibited elevation [(73.65±7.43 points, 72.24±7.23 points, 73.25±7.36 points, 70.24±7.05 points and 72.16±7.25 points) vs (81.25±8.14 points, 80.87±8.09 points, 81.43±8.15 points, 80.57±8.07 points and 81.32±8.14 points)] (P < .05).
CONCLUSION
Early microsurgical clipping of the tumor neck can downregulate risk of complications and cognitive impairment of cerebral aneurysm rupture and bleeding patients, which is worthy for clinical application.
PubMed: 38940784
DOI: No ID Found -
Scientific Reports Jun 2024Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a singular pathological entity necessitating early diagnostic approaches and both...
Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a singular pathological entity necessitating early diagnostic approaches and both prophylactic and curative interventions. This retrospective before-after study investigates the effects of a management strategy integrating perfusion computed tomography (CTP), vigilant clinical monitoring and standardized systemic administration of milrinone on the occurrence of delayed cerebral infarction (DCIn). The period included 277 patients, and the one 453. There was a higher prevalence of Modified Fisher score III/IV and more frequent diagnosis of vasospasm in the period. Conversely, the occurrence of DCIn was reduced with the management strategy (adjusted OR 0.48, 95% CI [0.26; 0.84]). Notably, delayed ischemic neurologic deficits were less prevalent at the time of vasospasm diagnosis (24 vs 11%, ), suggesting that CTP facilitated early detection. In patients diagnosed with vasospasm, intravenous milrinone was more frequently administered (80 vs 54%, ) and associated with superior hemodynamics. The present study from a large cohort of aSAH patients suggests, for one part, the interest of CTP in early diagnosis of vasospasm and DCI, and for the other the efficacy of CT perfusion-guided systemic administration of milrinone in both preventing and treating DCIn.
Topics: Humans; Subarachnoid Hemorrhage; Milrinone; Male; Female; Middle Aged; Cerebral Infarction; Retrospective Studies; Tomography, X-Ray Computed; Aged; Vasospasm, Intracranial; Adult; Administration, Intravenous
PubMed: 38937568
DOI: 10.1038/s41598-024-65706-w -
Experimental Neurology Jun 2024
PubMed: 38937164
DOI: 10.1016/j.expneurol.2024.114872 -
Neurologic Clinics Aug 2024Major advances in neurocritical care and the modalities used to treat aneurysms have led to improvement in the outlook of patients with aneurysmal subarachnoid... (Review)
Review
Major advances in neurocritical care and the modalities used to treat aneurysms have led to improvement in the outlook of patients with aneurysmal subarachnoid hemorrhage. Yet, several knowledge gaps remain widely open. Variability in practices stems from the lack of solid evidence to guide management, which recent guidelines from professional organizations aim to mitigate. In this article, the authors review some of these gaps in knowledge, highlight important messages from recent management guidelines, emphasize aspects of our practice that we consider particularly useful to optimize patient outcomes, and suggest future areas of research.
Topics: Subarachnoid Hemorrhage; Humans; Disease Management
PubMed: 38937037
DOI: 10.1016/j.ncl.2024.03.005 -
Molecular Neurobiology Jun 2024Neuroinflammation is a critical pathogenic event following hemorrhagic stroke. Endoplasmic reticulum (ER) stress-induced apoptosis and nucleotide-binding domain,...
Neuroinflammation is a critical pathogenic event following hemorrhagic stroke. Endoplasmic reticulum (ER) stress-induced apoptosis and nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3(NLRP3)-associated pyroptosis can contribute to the escalation of neuroinflammatory responses, leading to increased brain damage. G protein-coupled estrogen receptor 1(GPER1), as the most extensively characterized brain-derived estrogen, was reported to trigger neuroprotective effects. However, the anti-apoptotic and anti-pyroptotic effect of GPER1 activation and the underlying mechanism has not been fully elucidated. We established the experimental SAH model by intravascular perforation. The GPER1 selective agonist G1 was intravenously administered 1 h following SAH. For mechanistic exploration, the selective inhibitor of adenosine monophosphate-activated protein kinase (AMPK), dorsomorphin, was administered via intracerebroventricular injection 30 min prior to SAH induction. Post-SAH assessments included SAH grade, the short-term and long-term neurological outcomes, brain edema, cerebral blood flow, transmission electron microscopy (TEM), western blot (WB), ELISA, TUNEL staining, Fluoro-Jade C staining (FJC), and immunofluorescence staining. The expression of GPER1 was observed to elevate at 6 h and peaked at 24 h subsequent to SAH, predominantly co-localized with neurons. Post-treatment with G1 markedly ameliorated both the short-term and long-term neurological deficits of SAH mouse, as well as inhibiting the expression of neuronal ER stress-associated apoptotic proteins (i.e., CHOP, GRP78, Caspase-12, Cleaved Caspase-3, Bax, Bcl2) and pyroptosis-associated proteins (i.e., NLRP3, ASC, Cleaved Caspase-1). Additionally, our research revealed that inhibition of AMPK with dorsomorphin attenuated the neuroprotective effects of G1. This was accompanied by modifications in the molecular pathways associated with ER stress-induced apoptosis and pyroptosis. These data herein elucidated that GPER1 exerted neuroprotective effects by mitigating neuroinflammation in an AMPK-dependent manner, which modulates neuronal ER stress-associated apoptosis and pyroptosis. Boosting the anti-apoptotic and anti-pyroptotic effect by activating GPER1 may be an efficient treatment strategy for SAH patients.
PubMed: 38935231
DOI: 10.1007/s12035-024-04312-3