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OBJECTIVES@#Subarachnoid hemorrhage (SAH) is a serious cerebrovascular disease. Early brain injury (EBI) and cerebral vasospasm are the main reasons for poor prognosis of SAH patients. The specific inhibitor of histone deacetylase 6 (HDAC6), tubastatin A (TubA), has been proved to have a definite neuroprotective effect on a variety of animal models of acute and chronic central nervous system diseases. However, the neuroprotective effect of TubA on SAH remains unclear. This study aims to investigate the expression and localization of HDAC6 in the early stage of SAH, and to evaluate the protective effects of TubA on EBI and cerebral vasospasm after SAH and the underlying mechanisms.@*METHODS@#Adult male SD rats were treated with modified internal carotid artery puncture to establish SAH model. In the first part of the experiment, rats were randomly divided into 6 groups: a sham group, a SAH-3 h group, a SAH-6 h group, a SAH-12 h group, a SAH-24 h group, and a SAH-48 h group. At 3, 6, 12, and 24 h after SAH modeling, the injured cerebral cortex of rats in each group was taken for Western blotting to detect the expression of HDAC6. In addition, the distribution of HDAC6 in the cerebral cortex of the injured side was measured by immunofluorescence double staining in SAH-24 h group rats. In the second part, rats were randomly divided into 4 groups: a sham group, a SAH group, a SAH+TubAL group (giving 25 mg/kg TubA), and a SAH+TubAH group (giving 40 mg/kg TubA). At 24 h after modeling, the injured cerebral cortex tissue was taken for Western blotting to detect the expression levels of HDAC6, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining to detect apoptosis, and hematoxylin and eosin (HE) staining to detect the diameter of middle cerebral artery.@*RESULTS@#The protein expression of HDAC6 began to increase at 6 h after SAH (P<0.05), peaked at 24 h (P<0.001), and decreased at 48 h, but there was still a difference compared with the sham group (P<0.05). HDAC6 is mainly expressed in the cytoplasm of the neurons. Compared with the sham group, the neurological score was decreased significantly and brain water content was increased significantly in the SAH group (both P<0.01). Compared with the SAH group, the neurological score was increased significantly and brain water content was decreased significantly in the SAH+TubAH group (both P<0.05), while the improvement of the above indexes was not significant in the SAH+TubAL group (both P>0.05). Compared with the sham group, the expression of eNOS was significantly decreased (P<0.01) and the expressions of iNOS and HDAC6 were significantly increased (P<0.05 and P<0.01, respectively) in the SAH group. Compared with the SAH group, the expression of eNOS was significantly increased, and iNOS and HDAC6 were significantly decreased in the SAH+TubA group (all P<0.05). Compared with the SAH group, the number of TUNEL positive cells was significantly decreased and the diameter of middle cerebral artery was significantly increased in the SAH+TubA group (both P<0.05) .@*CONCLUSIONS@#HDAC6 is mainly expressed in neurons and is up-regulated in the cerebral cortex at the early stage of SAH. TubA has protective effects on EBI and cerebral vasospasm in SAH rats by reducing brain edema and cell apoptosis in the early stage of SAH. In addition, its effect of reducing cerebral vasospasm may be related to regulating the expression of eNOS and iNOS.
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Rats , Male , Animals , Rats, Sprague-Dawley , Subarachnoid Hemorrhage/drug therapy , Vasospasm, Intracranial/metabolism , Histone Deacetylase Inhibitors/therapeutic use , Neuroprotective Agents/therapeutic use , Histone Deacetylase 6/pharmacology , Apoptosis , Brain Injuries/drug therapyABSTRACT
@#Spontaneous subarachnoid haemorrhage (SAH) is a significant cause of stroke and may lead to severe neurological deficit or death. It is also associated with high morbidity and mortality for patients despite optimal medical and surgical treatment. Based on the World Health Organization the annual incidence of spontaneous SAH varies in different regions of the world between 2.0-22.5 per 100,000 populations with Finland and Japan having the highest incidence and South and Central America with lowest incidence.1
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Abstract Background: Aneurysmal subarachnoid hemorrhage is an important cause of premature death and disability worldwide. Magnesium sulphate is shown to have a neuroprotective effect and it reverses cerebral vasospasm. Milrinone is also used in the treatment of cerebral vasospasm. The aim of the present study was to compare the effect of prophylactic magnesium sulphate and milrinone on the incidence of cerebral vasospasm after subarachnoid hemorrhage. Methods: The study included 90 patients with aneurysmal subarachnoid hemorrhage classified randomly (by simple randomization) into two groups: magnesium sulphate was given as an infusion of 500 mg.day-1 without loading dose for 21 days. Group B: milrinone was given as an infusion of 0.5 µg.kg-1.min-1 without loading dose for 21 days. The cerebral vasospasm was diagnosed by mean cerebral blood flow velocity in the involved cerebral artery (mean flow velocity ≥ 120 cm.s-1), neurological deterioration by Glasgow coma scale, or angiography (the decrease in diameter of the involved cerebral artery >25%). Results: The mean cerebral blood flow velocity decreased significantly in the magnesium group compared to milrinone group through Day 7, Day 14 and Day 21 (p < 0.001). The incidence of cerebral vasospasm decreased significantly with magnesium compared to milrinone (p = 0.007). The Glasgow coma scale significantly improved in the magnesium group compared to milrinone group through Day 7, Day 14 and Day 21 (p = 0.036, p = 0.012, p = 0.016, respectively). The incidence of hypotension was higher with milrinone than magnesium (p = 0.012). Conclusions: The incidence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage was significantly lower and Glasgow coma scale significantly better with magnesium when compared to milrinone. Milrinone was associated with a higher incidence of hypotension and requirement for dopamine and norepinephrine when compared to magnesium.
Resumo Justificativa: A hemorragia subaracnoidea por aneurisma é uma importante causa de morte prematura e de incapacidade em todo o mundo. O sulfato de magnésio mostra um efeito neuroprotetor e reverte o vasoespasmo cerebral. A milrinona também é usada no tratamento de vasoespasmo cerebral. O objetivo do presente estudo foi comparar o efeito profilático do sulfato de magnésio e da milrinona sobre a incidência de vasoespasmo cerebral após hemorragia subaracnoidea. Métodos: O estudo incluiu 90 pacientes com hemorragia subaracnoidea por aneurisma randomicamente distribuídos (randomização simples) em dois grupos: sulfato de magnésio foi administrado em infusão de 500 mg.dia-1 sem dose de ataque durante 21 dias. O Grupo B recebeu milrinona em infusão de 0,5 µg.kg-1·min-1 sem dose de ataque durante 21 dias. O vasoespasmo cerebral foi diagnosticado pela velocidade média do fluxo sanguíneo cerebral na artéria cerebral envolvida (velocidade média do fluxo ≥ 120 cm.s-1), a deterioração neurológica por escala de coma de Glasgow ou angiografia (diminuição do diâmetro da artéria cerebral envolvida > 25%). Resultados: A velocidade média do fluxo sanguíneo cerebral diminuiu significativamente no grupo magnésio em comparação com o grupo milrinona nos dias 7, 14 e 21 (p < 0,001). A incidência de vasoespasmo cerebral diminuiu significativamente com o magnésio em comparação com milrinona (p = 0,007). A escala de coma de Glasgow melhorou significativamente no grupo magnésio em comparação com o grupo milrinona nos dias 7, 14 e 21 (p = 0,036, p = 0,012, p = 0,016, respectivamente). A incidência de hipotensão foi maior com milrinona do que com magnésio (p = 0,012). Conclusões: A incidência de vasoespasmo cerebral após hemorragia subaracnoidea por aneurisma foi significativamente menor e a escala de coma de Glasgow significativamente melhor com magnésio em comparação com milrinona. A milrinona foi associada a uma maior incidência de hipotensão e necessidade de dopamina e norepinefrina em comparação com o magnésio.
Subject(s)
Humans , Male , Female , Calcium Channel Blockers/therapeutic use , Milrinone/therapeutic use , Vasospasm, Intracranial/prevention & control , Phosphodiesterase 3 Inhibitors/therapeutic use , Magnesium Sulfate/therapeutic use , Subarachnoid Hemorrhage/complications , Double-Blind Method , Incidence , Vasospasm, Intracranial/etiology , Vasospasm, Intracranial/epidemiology , Middle AgedABSTRACT
Objective:To investigate the molecular mechanism of Buyang Huanwu Tang in improving cerebral vasospasm after subarachnoid hemorrhage. Method:Eighty male Sprague-Dawley rats were randomly divided into sham operation group, model group, Buyang Huanwu Tang low and high dose (13, 26 g·kg-1·d-1) group. According to 10 mL·kg-1, the drug was administered twice a day for 7 days. The subarachnoid hemorrhage model was made by double occipital pool injection method. The neurological function scores of rats in each group were evaluated at 1, 3, 5 and 7 days. The diameter of basilar artery was measured by hematoxylin-eosin (HE)staining. The expressions of phosphp-phosphoinositide 3-kinases(p-PI3K), phosphp-protein kinase B(p-Akt),endothelial nitric oxide synthase(eNOS) and neuronal nitric oxide synthase(nNOS) protein in basilar artery brain tissue were detected by Western blot. The expression of nitric oxide(NO) and endothelin-1(ET-1) in rat cerebrospinal fluid was detected by enzyme-linked immunosorbent assay (ELISA). Result:Compared with sham operation group, the neurological function scores of the model group were significantly decreased (PPPPP-1·d-1) increased the neurological function scores 3 to 5 days after treatment, and the basilar artery diameter was significant increased (PPPPPPPPPConclusion:The protective effect of Buyang Huanwu Tang on cerebral vasospasm after subarachnoid hemorrhage may be related to up-regulation of p-PI3K, p-Akt and eNOS expression in PI3K/Akt/eNOS signaling pathway, thereby increasing NO production.
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Subarachnoid hemorrhage (SAH) accounts for about 5% of all stroke patients, with high disability and mortality. Secondary cerebral vasospasm (CVS) after SAH interrupts cerebral blood flow to important parts of the brain, and then causes cerebral ischemia, which is one of the major complications of the disability and mortality. CVS usually occurring 3 to 12 days after SAH and lasted for an average of two weeks. The mechanism of CVS after SAH is very complex, and it is a process involving multiple factors and links, including hemolysis products, imbalance of vasodilator and vasoconstrictors, inflammation, activation of signal cascade reaction, apoptosis and expression of related genes. The treatment of CVS after SAH is divided into interventional therapy and drug therapy. Effective prediction, prevention, and treatment of CVS will significantly improve survival and quality of life after SAH. This article briefly reviews progress of the research on the mechanism and treatment of cerebral vasospasm after SAH.
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Objective To investigate the occurrence status quo and related factors of cerebral vasospasm after cerebral ruptured aneurysms embolization.Methods Sixty-six patients withruptured cerebral aneurysms undergoing embolization treatment were selected as the research subjects,and conducted routine aneurysm embolization treatment.The cerebral vasospasm occurrence rate during hospitalization period was statistically calculated,and the related factors of cerebral vasospasm after cerebral aneurysm rupture embolization were analyzed.Results The cerebral vasospasm occurrence rate was 22.73 ％.Age,body mass index (BMI),hypertension rate,smoking history,aneurysms number,Fisher grade,Hunt-Hess grade,operation timing and Glasgow coma index (GCS) had statistically significant difference between the patients with and without cerebral vasospasm (P＜0.05).The related factors of cerebral vasospasm after embolization of ruptured aneurysms were age,hypertension,smoking history,number of aneurysms,Fisher grade,Hunt-Hess grade,operation timing and GCS index.Conclusion The cerebral vasospasm rate after embolization of ruptured aneurysms is high,and related to age,hypertension,smoking history,number of aneurysms,Fisher grade,Hunt-Hess grade,operation timing and GCS index.
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Objective To investigate the value of cerebrospinal fluid drainage after aneurysm clipping in patients with intracranial aneurysm complicated with subarachnoid hemorrhage .Methods 84 intracranial aneurysms patients with subarachnoid hemorrhage were selected ,and they were randomly divided into study group (n =42) and control group (n =42).The control group used simple suture after aneurysm clipping ,the study group was given lumbar cistern drainage by implementation of the dural suture tube after aneurysm clipping .Before and after hydro-cephalus and cerebral vasospasm ,treatment changes of serum insulin-like growth factor 1 (IGF-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were compared between the two groups .Results The incidence rate of hydrocephalus of the study gruop was 4.8%,which was significantly lower than the 14.3% of the control group (χ2 =9.743,P <0.05).The incidence rate of cerebral vasospasm of the study group was 7.1%,which was significantly lower than 19.0% of the control group (χ2 =11.802,P <0.05).The incidence rates of intracranial infection,cerebrospinal fluid leakage and other complications between the two groups had no statistically significant differences (χ2 =2.074,2.125,all P >0.05).The serum levels of IGF-1 and sVCAM-1 between the two groups had no statistically significant differences before operation (t =0.417,0.603,all P >0.05).At the 8th day after oper-ation,the serum levels of sVCAM-1 and IGF-1 of the study group were significantly lower than those of the control group (t =7.335,6.856,all P <0.05).Conclusion After aneurysm clipping,the lumbar cistern drainage tube drainage is beneficial to reduce hydrocephalus and cerebral vasospasm incidence ,inhibit the expression of serum IGF-1,sVCAM-1,with less adverse reactions,it is worthy of application.
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One of the majority reasons for mortality and morbidity in children is cerebral vasospasm secondary to intracranial hemorrhage(CVSIH).CVSIH prevented and treated by nimodipine in adult patients have been widely reported in China and abroad,but only limited reports in children.We aimed to describe the mechanism and diagnosis of CVSIH in children,and also the mechanism,efficacy and safety of nimodipine.
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Objective To explore the persistent cerebrospinal fluid drainage and intrathecal injection of urokinase in prevention and treatment of cerebral vasospasm after aneurysm surgery.Methods The effect of prevention and treatment of cerebral vasospasm after aneurysm surgery in 40 patients, using the method combined with intrathecal injection of urine kinase for persistent cerebrospinal fluid drainage, and classified as the observation group;the other 40 cases patients with persistent cerebrospinal fluid drainage intervention, and classified as the control group, two groups of patients were in Shandong Provincial Hospital from January 2016 to January 2017.Results The incidence of rebleeding in two groups had no significant difference in observation of cerebral vasospasm in patients with the incidence was significantly lower than the control group, the observation The incidence of cerebral vasospasm group was 15.0%, 37.5% in the control group, compared two groups of patients with the prognosis, the obvious observation group of patients with good prognosis, comparison between groups showed significantly(P<0.05).Conclusion Persistent cerebrospinal fluid drainage and intrathecal injection of urokinase on the clinical study of postoperative cerebral vasospasm aneurysm found the simple, compared with continuous drainage of cerebrospinal fluid, can improve the clinical condition of patients, and promote the recovery of patients, reduce cerebral vascular spasm, so it is worthy of reference.
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Aim To evaluate the efficacy and safety of different routes for vinpocetine injection by intravenous or trans-angiographic catheter on cerebral vasospasm(CVS).Methods A total of 105 aneurysmal subarachnoid hemorrhage(aSAH)patients with CVS following intracranial aneurysm embolization were chosen and randomly divided into group C, B and A, with 35 cases in each group.Patients in group C were treated with 3H therapeutic regimen, while those in group B and A were with 3H therapeutic regimen plus vinpocetine by intravenous injection or trans-angiographic catheter, respectively.The index including middle cerebral artery(MCA) blood flow velocity, National Institutes of Health stroke scale(NIHSS) score, Glasgow outcome scale(GOS) grading, clinical efficacy, hypotension rate and rehaemorrhagia rate were detected and compared among three groups.Results After the 7 d and 14 d treatment, the MCA blood flow velocity of group A and B was observed to be significantly lower than that of group C(P0.05) observed in the hypotension rate between group A and C.Also, there was no statistical difference(P>0.05)found in the rehaemorrhagia rate among three groups.However, the GOS grading of group A and B was significantly better than that of group C(P<0.05), and the grading of group A was significantly better than that of group B(P<0.05)after 3 months treatment.Conclusions Using vinpocetine by intravascular injection or by trans-angiographic catheter could be the efficient treatment for the CVS after intracranial aneurysm embolization, and vinpocetine injection by trans-angiographic catheter is the better mode of administration with the consideration of efficacy and safety.
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Objective To investigate the efficacy of super selective intra-arterial infusion of verapamil for the treatment of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH).Methods From January 2013 to February 2016,the clinical data of 15 patients with subarachnoid hemorrhage (SAH) who had CVS after intracranial aneurysm clipping (n=8) or endovascular treatment (n=7) were analyzed retrospectively.All patients received whole brain digital subtraction angiography (DSA).Microcatheter super selection to spastic arteries was used and verapamil (11.1±3.4 mg) was infused.The findings of whole brain DSA before and after treatments were compared.The blood pressure and heart rate were collected during the treatment and the findings of transcranial Doppler ultrasonography were recorded.The patients were followed up for 6 months and the Glasgow outcome scale (GCS) scores were obtained.Results (1) A total of 20 intra-arterial infusion treatments were performed in 15 cases.They were compared before and after perfusion.CVS was improved on DSA in 14 cases,there was no significant change in on cases.(2) Transcranial Doppler ultrasonography showed that the mean blood flow velocity (mBFV) of the middle cerebral artery was decreased from 181±4 cm/s before the super selective intra-arterial infusion to 126±4 cm/s within 1 hour after treatment.There was significant difference (t=42.46,P0.05).(4) All patients were followed up for 6 months.The GOS score at 6 months:good recovery in 9 cases,moderate disability but could take care of themselves in 3 cases,severe disability and could not take care of themselves in 3 cases,no persistent vegetative state or death.Conclusion Super selective intra-arterial infusion of verapamil can effectively improve the treatment of aneurysmal SAH caused CVS.At the same time,it has no obvious effect on blood pressure and heart rate.
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Objective To assess the clinical effects of individual nursing in the prevention of cerebral va-sospasm(CVS)in perioperative intracranial aneurysm intervention based on the therapy use of ligustrazine. Meth-ods Patients who suffered intracranial aneurysm from January 2014 to June 2017 in our hospital were divided into two groups randomly.Normal nursing was applied in the control group,while individual nursing was used for the ex-perimental group. Ligustrazine was used in both groups. Results A total of 56 patients were included in this re-search,28 for the control group,and 28 for the other group.Most patients recovered well and discharged regularly. The incidence rate of CVS in the experimental group(3.57%)was significant lower than that in the control group (28.57%)(P<0.05).Conclusions Based on the fact that individual nursing could lower the incidence of CVS of patients who suffered intracranial aneurysms when ligustrazine was used,it is one of the most important way to pro-mote the recovery as well as lower the mortality rate of patients.
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Objective·To observe the degree of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) at different time points, and to investigate the effects of ethyl pyruvate (EP) on CVS following SAH and its mechanism. Methods·Fifty healthy SD rats were randomly divided into five groups i.e. sham group, SAH-3 d group, SAH-5 d group, SAH-7 d group and SAH-9 d group (n=10 in each group). Sham group was built by double cisternal injection with 0.3 mL saline each time, and SAH group was built by double cisternal injection with 0.3 mL autologous blood each time. The neurological function and degree of CVS were observed. Another forty-eight healthy SD rats were randomly divided into three groups i.e. sham+saline (equal volume) group, SAH+saline (equal volume) group and SAH+EP [100 mg/(kg·d)] group (n=16 in each group). The neurological function, degree of CVS and cell apoptosis of basilar artery were observed on day 7. The expressions of p-Akt, Bax, Bcl-2 and cleaved caspase-3 were also observed on day 7. Results·CVS significantly increased on day 3, decreased on day 5, and then significantly increased to top level on day 7, and gradually decreased on day 9. Compared with sham+saline group, the neurological scores were significantly decreased in SAH+saline group on day 7. Compared with sham+saline group, CVS and cell apoptosis of basilar artery were significantly increased in SAH+saline group on day 7. Compared with sham+saline group, the expressions of Bax and cleaved caspase-3 were significantly up-regulated, while the expressions of p-Akt and Bcl-2 were significantly down-regulated in SAH+saline group on day 7. Compared with SAH+saline group, the neurological scores significantly increased in SAH+EP group on day 7. Compared with SAH+saline group, CVS and cell apoptosis of basilar artery significantly decreased in SAH+EP group on day 7. Compared with SAH+saline group, the expressions of Bax and cleaved caspase-3 were significantly down-regulated, while the expressions of p-Akt and Bcl-2 were significantly up-regulated in SAH+EP group on day 7. Conclusion·The double hemorrhage model rat has most severely CVS on day 7. EP can attenuate vasospasm after SAH, and its mechanism may be associated with inhibition of cell apoptosis. PI3K/Akt signaling pathway may be involved, which may provide a novel therapeutic target for CVS.
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Objective To investigate the genetic association between endothelin receptor type A(EDNRA)gene polymor-phism and delayed cerebral vasospasm(DCVS)in patients with aneurysmal subarachnoid hemorrhage(aSAH).Methods 133 aSAH patients from January 2015 to January 2017 were recruited to participate in the study.According to whether com-bined with DCVS,they were divided into the DCVS group(78 cases)and the control group(55 cases).Genotype was deter-mined by polymerase chain reaction-restriction fragment length polymorphism combined with DNA direct sequencing tech-nique for the polymorphism of the EDNRA gene.Results Samples of DCVS group and control group both were consistent with Hardy-Weinberg's law of inheritance(χ2=0.295,P=0.863;χ2=0.652,P=0.722).There were significant differ-ences of EDNRA gene rs5335 polymorphism between DCVS group and control group,under allele model(χ2=4.213,P=0.040)and the dominant model(χ2=4.790,P=0.029).However,there was no difference of EDNRA gene polymorphism between DCVS group and control group under recessive model(χ2=1.299,P=0.254).Multivariate Logistic regression a-nalysis showed that allele C was protective factor of DCVS for aSAH patients(OR=0.572,95%CI 0.401~0.872,P=0.021).Conclusion For aSAH patients,EDNRA gene rs5335 polymorphism may closely related to DCVS.
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An 8-month old female presented with spontaneous subarachnoid hemorrhage and was treated successfully with endovascular coil embolization of the ruptured aneurysm. Transcranial Doppler ultrasound performed four days later demonstrated middle cerebral artery (MCA) velocities greater than 350 cm/sec on the right and greater than 200 cm/sec on the left, despite medical management. The patient demonstrated no focal neurological deficits, though examination was limited by our patient's sedation and intubation. Angiography revealed severe vasospasm of the supraclinoid internal carotid and MCA territories, bilaterally. The vasospasm was refractory to the administration of intra-arterial verapamil. Balloon angioplasty was attempted, but the device could not be advanced safely due to the small size of the patient's vessels and the stiffness of the device. A microcatheter (0.0165" diameter) was advanced over a J-shaped soft microwire (0.014" diameter) to perform mechanical angioplasty in the internal carotid artery and MCA vessels bilaterally. Dramatic improvement was seen angiographically and on transcranial Doppler, and no complications were seen.
Subject(s)
Female , Humans , Infant , Aneurysm , Aneurysm, Ruptured , Angiography , Angioplasty , Angioplasty, Balloon , Carotid Artery, Internal , Embolization, Therapeutic , Intubation , Middle Cerebral Artery , Subarachnoid Hemorrhage , Ultrasonography , Vasospasm, Intracranial , VerapamilABSTRACT
Therapeutic hypothermia (TH) improves the neurological outcome in patients after cardiac arrest and neonatal hypoxic brain injury. We studied the safety and feasibility of mild TH in patients with poor-grade subarachnoid hemorrhage (SAH) after successful treatment. Patients were allocated randomly to either the TH group (34.5°C) or control group after successful clipping or coil embolization. Eleven patients received TH for 48 hours followed by 48 hours of slow rewarming. Vasospasm, delayed cerebral ischemia (DCI), functional outcome, mortality, and safety profiles were compared between groups. We enrolled 22 patients with poor-grade SAH (Hunt & Hess Scale 4, 5 and modified Fisher Scale 3, 4). In the TH group, 10 of 11 (90.9%) patients had a core body temperature of 95% of the 48-hour treatment period. Fewer patients in the TH than control group (n = 11, each) had symptomatic vasospasms (18.1% vs. 36.4%, respectively) and DCI (36.3% vs. 45.6%, respectively), but these differences were not statistically significant. At 3 months, 54.5% of the TH group had a good-to-moderate functional outcome (0–3 on the modified Rankin Scale [mRS]) compared with 9.0% in the control group (P = 0.089). Mortality at 1 month was 36.3% in the control group compared with 0.0% in the TH group (P = 0.090). Mild TH is feasible and can be safely used in patients with poor-grade SAH. Additionally, it may reduce the risk of vasospasm and DCI, improving the functional outcomes and reducing mortality. A larger randomized controlled trial is warranted.
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Humans , Aneurysm , Body Temperature , Brain Injuries , Brain Ischemia , Embolization, Therapeutic , Heart Arrest , Hypothermia, Induced , Mortality , Pilot Projects , Prospective Studies , Rewarming , Subarachnoid Hemorrhage , Vasospasm, IntracranialABSTRACT
Objective: To investigate the dynamic changes of mitofusin-2 (Mfn2) expression in rat cerebral arteries after experimental subarachnoid hemorrhage (SAH) and to reveal the relationship between Mfn2 and cerebral vasospasm (CVS). Methods: A SAH model was induced by endovascular perforation of the intracranial portion of the internal carotid artery. One hundred and forty six male SD rats were randomly divided into six groups; sham group and SAH groups which were sacrificed at different time points (24 hours, 48 hours, 72 hours, 7days and 14days). Mortality, neurobehavioral score and brain water content were measured. Histology was conducted to observe the morphological changes. Western blotting and RT-PCR were performed to measure the Mfn2 protein and mRNA changes of the major cerebral arteries at different time points after SAH. Results: Blood clot surrounded the basilar artery gradually dissipated after SAH. HE staining showed that the most severe morphological vasospasm in basilar arteries was observed at the 24th hour after SAH. No positive immunohistochemical staining of Mfn2 was shown in the media layer of basilar artery at the 7th day after SAH. Western blotting showed that Mfn2 protein was remarkably increased at the 48th hour and the 72th hour after SAH compared to sham groups (P < 0. 05) and significantly decreased at the 7th day after SAH (p < 0. 05). The protein level at the 14th day after SAH was almost the same level with the sham and SAH 24 hours groups. The mRNA level changed in the same tendency as the protein level. Conclusion: This study indicate that Mfn2 plays essential roles in both acute and delayed CVS which may provide a theoretical basis for understanding of the mechanism of the CVS after SAH.
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Background: Intracranial aneurysms may rupture and are typically associated with high morbidity and mortality, commonly due to vasospasm after rupture. Once the aneurysm ruptures, the patient’s cerebral blood flow may be disturbed during the acute phase, affecting cerebral circulation and thus cerebral perfusion prior to the onset of vasospasm. Fisher and Navarro scores are used to predict vasospasm, while World Federation of Neurosurgical Societies (WFNS) scores are used to predict patient outcomes. Several score modifications are available to obtain higher sensitivity and specificity for the prediction of vasospasm development, but these scores are still unsuccessful. Alternatively, cerebral CT perfusion scan (CTP) is a non-invasive method for measuring cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) in regions of interests (ROI) to obtain the cerebral perfusion status as well as detecting vasospasm. Methods: A total of 30 patients’ data with clipped anterior circulation intracranial aneurysms admitted to the hospital between 1 January 2013 and 30 June 2014, were collected from the hospital’s electronic database. The data collected included patients’ admissions demographic profiles, Fisher, Navarro and WFNS scores; and their immediate pre- and postoperative CTP parameters. Results: This study found a significant increase in post-operative MTT (pre- and postoperative MTT) were 9.75 (SD = 1.31) and 10.44 (SD = 1.56) respectively, (P < 0.001)) as well as a significant reduction in post-operative CBF (pre- and post-operative mean CBF were 195.29 (SD = 24.92) and 179.49 (SD = 31.17) respectively (P < 0.001)). There were no significant differences in CBV. There were no significant correlations between the pre- and post-operative CTP parameters and Fisher, Navarro or WFNS scores. Conclusion: Despite the interest in using Fisher, Navarro and WFNS scores to predict vasospasm and patient outcomes for ruptured intracranial aneurysms, this study found no significant correlations between these scores in either pre- or post-operative CTP parameters. These results explain the disagreement in the field regarding the multiple proposed grading systems for vasospasm prediction. CTP measures more than just anatomical structures; therefore, it is more sensitive towards minor changes in cerebral perfusion that would not be detected by WFNS, Fisher or Navarro scores.
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La presente revisión del tema Vasoespasmo y Déficit Isquémico Cerebral tardío (DIT) en la Hemorragia subaracnoidea aneurismática tiene como objetivo actualizar su manejo, basado en las hipótesis mas aceptadas que se han logrado para explicar su patogénesis. Se efectúa una introducción con conceptos generales, se revisan las bases patogénicas del Vasoespasmo y se plantea su manejo, tomando en cuenta su diagnóstico, monitorización, profilaxis y manejo avanzado de acuerdo a las últimas Guías de Manejo Clínico y según medicina basada en las evidencias.
The objective of the present review on cerebral vasospasm and cerebral delayed isquemic deficit due to subarachnoid haemorrhage secondary to ruptured cerebral aneurysm, is to update their management, based on the most accepted pathophysiological hypotesis explaining their pathogenetic mechanisms. An introduction is performed presenting general concepts, review of the most recent research works explaining their pathogenesis, and the management is stated touching diagnosis, monitoring, prophylaxis, and advanced management according with the last clinical guidelines for his management using medicine based on evidences.
Subject(s)
Humans , Male , Female , Aneurysm, Ruptured , Brain Ischemia , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/drug therapy , Intracranial Aneurysm , Vasospasm, Intracranial/etiology , Vasospasm, Intracranial/drug therapy , Circle of Willis/pathology , Neurophysiological Monitoring/methods , Severity of Illness Index , Tomography, Spiral Computed/methodsABSTRACT
Objetivo: presentar dos casos de muerte materna asociados al uso de medicamentos derivados del ergot (ergotismo agudo severo), y realizar una revisión de la literatura de la presentación de eventos adversos en el sistema nervioso central en puérperas expuestas a estos medicamentos. Materiales y métodos: se presentan dos casos de muerte materna posparto, el primero se asoció al uso de bromocriptina para supresión de lactancia y el segundo al uso metilergometrina para controlar hemorragia poscesárea. Las pacientes fueron atendidas en instituciones de tercer nivel de complejidad en la ciudad de Medellín, Colombia. Se realizó revisión de la literatura, registrada en la base de datos Medline vía PubMed. Los términos empleados para la búsqueda fueron: derivados del ergot, bromocriptina, angeítis cerebral posparto, ergotismo, enfermedad vascular cerebral posparto. Se buscaron, sin límite de tiempo, reportes de caso, reportes de series de caso y revisiones de tema. Se buscaron informes o alertas de seguridad de agencias reguladoras tales como: la Federal Drugs Administration (FDA), la European Medicines Agency (EMA) y del Instituto Nacional de Vigilancia de Medicamentos y Alimentos (Invima). Se consultaron artículos en inglés, francés y español. Resultados: se incluyeron 16 publicaciones que cumplieron con los criterios de búsqueda. Se lograron identificar 33 casos. Dos fueron fatales, uno asociado al uso de metilergonovina venosa para el alumbramiento y el otro a ergometrina oral usado como abortivo en la semana 20 de gestación. En las neuroimágenes predominan los hallazgos isquémicos (sugestivos de vasoespasmo cerebral). En tres casos se reportó hemorragia intracerebral, uno de estos fue un caso fatal. Los síntomas más frecuentes de presentación fueron la cefalea intensa, seguida de la convulsión. Solo en nueve casos se logró identificar el antecedente de hipertensión o preeclampsia, y en cuatro migraña. La indicación para el uso de bromocriptina en todos los casos fue suprimir la lactancia. En los tres casos reportados en que se usó metilergonovina fue para realizar alumbramiento. En el sistema de farmacovigilancia colombiano no se encontraron reportes de eventos adversos serios asociados a estos medicamentos. Conclusión: se debe reconocer el ergotismo del sistema nervioso central en el puerperio por el uso de medicamentos tales como la bromocriptina y la metilergonovina, como una entidad potencialmente fatal. Es importante crear una cultura de reporte de eventos adversos serios de estos medicamentos en nuestro país.
Objective: To report two cases of maternal death associated with ergot-derived drugs (acute sever ergotism), and to conduct and review of the literature on central nervous system adverse events during the postpartum period in women exposed to these medications. Materials and methods: Two cases of maternal death during the postpartum period. The first was associated with the use of bromocriptine for breast milk suppression, and the second was associated with the use of methylergometrine for the control of bleeding after Cesarean section. The patients received care at Level III institutions in the city of Medellín, Colombia. A review of the literature was conducted in the Medline database through Pubmed. The terms used for the search were: ergot derivatives, bromocriptine, postpartum cerebralangiitis, ergotism, postpartum cerebral vascular disease. The search was conducted without a time limitation and included, case reports, case series reports, and reviews. The search also included safety reports or alerts from regulatory agencies such as the FDA, the European Medicines Agency (EMA), and Invima. Articles in English, French and Spanish were reviewed. Results: Overall, 16 publications that met the search criteria were included, and 33 cases were identified. Two of the cases were fatal, one associated with the use of intravenous methylergonovine for delivery and the second one was associated with the use of oral ergometrine to induce abortion at 20 weeks of gestation. Neuroimaging studies show, predominantly, ischemic findings (suggestive of cerebral vasospasm). In three cases, intracranial haemorrhage was reported, and one of the three cases was fatal. The most frequent presenting symptoms were intense headache, followed by seizures. It was possible to identify a history of hypertension and/or preeclampsia only in nine cases, and a history of migraine in four. The vast majority of patients were otherwise healthy. In all the cases, the indication for using bromocriptine was breast milk suppression. In the three reported cases in which methylergonovine was used, the indication was to assist delivery. No reports of serious adverse events associated with these drugs were found in the Colombian pharmacovigilance system. Conclusion: Ergotism of the central nervous system due to the use of drugs such as bromocriptine and methylergonovine must be recognised during the postpartum period because it is life-threatening. It is important to create a culture of reporting of serious adverse events associated with these medications in our country.