Overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treatment of intracerebral hemorrhage / 中国中药杂志

To overview of systematic reviews/Meta-analysis of Xingnaojing Injection(XNJ) in the treatment of intracerebral hemorrhage(ICH). The systematic reviews concerning XNJ in the treatment of ICH were retrieved from four Chinese databases, four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, with the retrieval time set from their inception to September 2020. Following the independent screening and data extraction by two researchers, a measurement tool to assess systematic evaluation 2(AMSTAR 2) and grades of recommendation, assessment, development and evaluation(GRADE) system were used to evaluate the metho-dological, reporting and evidence qualities of the 10 included systematic reviews. The results showed that XNJ was superior to the wes-tern medicine or conventional treatment in improving the effective rate and National Institutes of Health stroke scale(NIHSS) score, Barthel index(BI), and Glasgow coma scale(GCS) score and Chinese stroke scale(CSS) score, and reducing the mortality and cerebral hematoma volume, without inducing obvious adverse reactions. In general, the methodological, reporting and evidence qualities of the 10 included systematic reviews were poor. The AMSTAR 2 scores showed that key items No. 2 and No. 16 failed to meet the stan-dard, resulting in poor methodological quality. There was only one outcome indicator graded by GRADE as intermediate quality, 43% indicators as low quality, 42% indicators as extremely low quality, and none as high quality. These available evidences have suggested that the methodological, reporting and evidence qualities of the systematic evaluation concerning XNJ for the treatment of ICH need to be improved. Most evidences support that XNJ was better than the western medicine or conventional treatment in the treatment of ICH, but the methodological quality and the reliability of outcome indicators in relevant systematic review were low. More high-quality studies are still required for further verification.

Pharmacological Activation of RXR-α Promotes Hematoma Absorption via a PPAR-γ-dependent Pathway After Intracerebral Hemorrhage / 神经科学通报·英文版

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.

The neuroprotection of cerebrolysin after spontaneous intracerebral hemorrhage through regulates necroptosis via Akt/ GSK3B signaling pathway

ABSTRACT Purpose: Spontaneous intracerebral hemorrhage (ICH) is a major cause of death and disability with a huge economic burden worldwide. Cerebrolysin (CBL) has been previously used as a nootropic drug. Necroptosis is a programmed cell death mechanism that plays a vital role in neuronal cell death after ICH. However, the precise role of necroptosis in CBL neuroprotection following ICH has not been confirmed. Methods: In the present study, we aimed to investigate the neuroprotective effects and potential molecular mechanisms of CBL in ICH-induced early brain injury (EBI) by regulating neural necroptosis in the C57BL/6 mice model. Mortality, neurological score, brain water content, and neuronal death were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, Evans blue extravasation, Western blotting, and quantitative real-time polymerase chain reaction (PCR). Results: The results show that CBL treatment markedly increased the survival rate, neurological score, and neuron survival, and downregulated the protein expression of RIP1 and RIP3, which indicated that CBL-mediated inhibition of necroptosis, and ameliorated neuronal death after ICH. The neuroprotective capacity of CBL is partly dependent on the Akt/GSK3β signaling pathway. Conclusions: CBL improves neurological outcomes in mice and reduces neuronal death by protecting against neural necroptosis.

Systematic review of efficacy and safety of Angong Niuhuang Pills in adjuvant treatment of cerebral hemorrhage / 中国中药杂志

To systematically review the efficacy and safety of Angong Niuhuang Pills in adjuvant treatment of cerebral hemorrhage. CNKI, VIP, Wanfang, CBM, PubMed, EMbase, Cochrane Library were retrieved to collect the randomized controlled trial(RCT) from the time of database establishment to November 2020. Two researchers screened out the literatures and extracted the data according to the inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis. A total of 13 RCTs were included, involving 1 196 patients with cerebral hemorrhage, with 599 in the treatment group and 597 in the control group, and all of them were treated with internal medicine. The results of Meta-analysis showed that compared with conventional therapy, the combined administration with Angong Niuhuang Pills could improve the effective rate in patients with cerebral hemorrhage(RR=1.25, 95%CI[1.18, 1.34], P<0.000 01), the National Institutes of Health stroke scale(NIHSS)score(MD=-5.18, 95%CI[-8.12,-2.23], P=0.000 6) and Glasgow coma scale(GCS) score(MD=1.12, 95%CI[0.46, 1.78], P=0.000 9), activity of daily living(ADL)(MD=15.70, 95%CI[14.05, 17.36 ], P<0.000 01), reduce the malondialdehyde(MDA)(MD=-1.73,95%CI[-2.81,-0.64],P=0.002), but with no statistically significant difference in hematoma volume changes between the two groups. In terms of safety, the combined administration with Angong Niuhuang Pills reduced the incidence of adverse reactions compared with the single administration of conventional therapy(RR=0.40, 95%CI[0.28, 0.57], P<0.000 01), with no serious adverse events. The existing clinical study evidences show that Angong Niuhuang Pills had a good effect in adjuvant treatment of cerebral hemorrhage, and can improve the treatment efficacy, activity of daily living and symptoms of neurological deficits, and reduce oxidative stress, with a higher safety. However, the methodological quality of the included studies is not high, so the above conclusions still need to be verified with more high-quality studies.

Ictus hemorrágico en los servicios clínicos del hospital José R López Tabrane: primer cuatrimestre del 2012 / Hemorrhagic ictus at the clinical services of the hospital José R. López Tabrane: First quarter of 2012

Se realizó un estudio descriptivo del seguimiento a 14 pacientes que ingresaron con el diagnóstico clínico y radiológico de enfermedad cerebrovascular hemorrágica en los servicios clínicos del hospital José Ramón López Tabrane de Matanzas, en el periodo de enero a abril del 2012. Se observa que el grupo de 66–75 años predominó con 6 casos para un 42,8 por ciento, siendo el sexo masculino el más afectado con 8 pacientes para un 57,1 por ciento. Se apreció una estrecha relación entre escala de Glasgow, evolución clínica y estado al egreso. Se observó con escala Glasgow 15/15 solo 1 paciente vivo, para un 7,1 por ciento; con escala de 9-14/15 hubo 9 pacientes para un 64,2 por ciento y dentro de estos 4 fallecidos para una letalidad de 44,4 por ciento, con Glasgow de menos de 8/15 se presentaron 4 pacientes que todos fallecieron para una letalidad del 100 por ciento. Se comprueba mediante estudios de neuroimagen que el 24,1 por ciento son hemorragias e infarto sin efecto de masa, el 57,1 por ciento son hemorragias con efecto de masa, el 14,2 por ciento son hemorragias subaracnoideas y el 7,1 por ciento corresponde a la hemorragia intraventricular. El 100 por ciento de los pacientes recibieron tratamiento convencional, la alimentación precoz se utilizó en 10 pacientes para un 71,4 por ciento. La estadía hospitalaria se comportó entre 2 y 15 días. Se muestra la presencia de factores de riesgo en los pacientes estudiados. Se concluye que la escala de Glasgow permite establecer un pronóstico de morbimortalidad de los pacientes que ingresan con enfermedad cerebrovascular hemorrágica.

We carried out a descriptive study of the follow up of 14 patients who entered the clinical services of the hospital José R. López Tabrane, of Matanzas, with the radiological and clinical diagnosis of hemorrhagic cerebral vascular disease, in the period form January to April 2012. We observed that there was a predominance of the 66-75-years-old age group with 6 cases for 42,8 percent, being the male genre the most affected with 6 patients for 57,1 percent. We found a tight relation among Glasgow scale, clinical evolution and health status at discharge. It was observed only one alive patient, 7,1 percent, with Glasgow scale 15/15; with Glasgow scale value 9-14/15 there were 9 patients for 64,2 percent, among them 4 passed away for 44,4 percent lethality; with Glasgow scale of less than 8/15 there were 4 patients; all of them died for 100 percent lethality. Through neuro-imaging studies we verified that 34,1 percent of the cases are hemorrhages and infarct without mass effect, 57,1 percent are hemorrhages with mass effect, 14,2 percent are sub-arachnoid hemorrhages, and 7,1 percent are intra-ventricular hemorrhages. 100 percent of the patients received conventional treatment, precocious feeding was used in 10 patients for 71,4. Hospital staying ranged between 2 and 15 days. It was showed the presence of risk factors in the studied patients. We arrived to the conclusion that the Glasgow scale allows to establish a morbimortality prognosis of the patients entering with hemorrhagic cerebral vascular disease.

Antihypertensive Treatment of Acute Intracerebral Hemorrhage by Intravenous Nicardipine Hydrochloride: Prospective Multi-Center Study

The authors performed a multicenter prospective study to evaluate the feasibility and safety of intravenous nicardipine hydrochloride for acute hypertension in patients with intracerebral hemorrhage (ICH). This study included 88 patients (mean age: 58.3 yr, range 26-87 yr) with ICH and acute hypertension in 5 medical centers between August 2008 and November 2010, who were treated using intravenous nicardipine. Administration of nicardipine resulted in a decrease from mean systolic blood pressure (BP) (175.4 +/- 33.7 mmHg) and diastolic BP (100.8 +/- 22 mmHg) at admission to mean systolic BP (127.4 +/- 16.7 mmHg) and diastolic BP (67.2 +/- 12.9 mmHg) in 6 hr after infusion (P or = 2) was observed in 2 (2.2%) of 88 patients during the treatment. Aggressive nicardipine treatment of acute hypertension in patients with ICH can be safe and effective with a low rate of neurological deterioration and hematoma expansion.

Outcomes from intracerebral hemorrhage among patients pre-treated with statins / Prognóstico da hemorragia intracerebral em pacientes previamente tratados com estatinas

OBJECTIVE: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been associated with improved clinical outcomes after ischemic stroke and subarachnoid hemorrhage, but with an increased risk of incidental spontaneous intracerebral hemorrhage (ICH). We investigated whether the statin use before ICH, was associated with functional independence, 90 days after treatment. METHOD: We analyzed 124 consecutive ICH patients with 90-day outcome data who were enrolled in a prospective cohort study between 2006 and 2009. Eighty-three patients were included in this study. Among ICH survivors, univariate Cox regression models and Kaplan-Meier plots were used to determine subject characteristics that were associated with an increased risk of recurrence. Statin usage was determined through interviewing the patient at the time of ICH and confirmed by reviewing their medical records. Independent status was defined as Glasgow Outcome Scale grades 4 or 5. RESULTS: Statins were used by 20 out of 83 patients (24 percent) before ICH onset. There was no effect from pre-ICH statin use on functional independence rates (28 percent versus 29 percent, P=0.84) or mortality (46 percent versus 45 percent, P=0.93). CONCLUSION: Pre-ICH statin use is not associated with changes to ICH functional outcome or mortality.

OBJETIVO: Inibidores da 3-hydroxy-3-methylglutaryl coenzima A (HMG-CoA) redutase, ou estatinas, têm sido associados com melhora do prognóstico após eventos encefálicos isquêmicos e hemorragia subaracnóidea, mas com um aumento do risco de evento encefálico hemorrágico (AVEh). Nós investigamos se o uso de estatinas prévio ao sangramento é associado com independência funcional em 90 dias. MÉTODO: Analisamos 124 pacientes consecutivos com AVEh com 90 dias de seguimento, selecionando 83 para um estudo coorte prospectivo entre 2006 e 2009. O uso de estatinas foi determinado pela entrevista ao paciente no momento da entrada ao hospital e complementado pela revisão do prontuário. Foi definido como independência funcional um GOS (Glasgow Outcome Scale) 4 ou 5. RESULTADOS: Estatinas eram usadas por 20/83 (24 por cento) antes do AVEh. Não houve efeito benéfico do uso prévio ao AVEh de estatinas nas taxas de independência funcional (28 por cento versus 29 por cento, P=0,84) ou mortalidade (46 por cento versus 45 por cento, P=0,93). CONCLUSÃO: O uso de estatina pré-AVEh não é associado com melhora do prognóstico funcional ou taxa de mortalidade.

Uso antenatal do corticosteroide e hemorragia peri-intraventricular: [revisão] / Antenatal corticosteroids and intraventricular hemorrhage: [review]

OBJETIVO: Realizar uma revisão bibliográfica sobre o uso antenatal do corticosteroide na prevenção da hemorragia peri-intraventricular. FONTES DE DADOS: Levantamento bibliográfico por meio do Pubmed e SciELO abrangendo os últimos 20 anos. Foram utilizadas as palavras chaves no idioma inglês: "cerebral hemorrhage", "steroids" e "newborn, infant". SÍNTESES DE DADOS: A hemorragia peri-intraventricular é uma importante patologia nos prematuros, sobretudo nos menores de 34 semanas, devido a suas graves sequelas neurológicas. Uma vez ocorrido o sangramento, não há tratamento específico. Desta forma, a prevenção torna-se o maior objetivo das pesquisas. O resultado da meta-análise de estudos randomizados demonstrou que o corticosteroide antenatal reduz a mortalidade e a incidência da doença de membrana hialina e da hemorragia peri-intraventricular. O efeito protetor na redução do risco da hemorragia peri-intraventricular não está completamente esclarecido. Além de acelerar a maturidade pulmonar, o corticosteroide antenatal estimula a maturação da microvasculatura da matriz germinativa, promove o espessamento da membrana basal, acelera a formação proteica nas junções firmes e estabiliza o fluxo sanguíneo cerebral. Também melhora as condições de nascimento dos fetos pré-termo. CONCLUSÕES: O uso antenatal do corticosteroide associado à implementação de melhores práticas de atendimento ao prematuro tem sido responsável pela evidente redução dos índices dessa doença. Apesar de comprovada eficácia e segurança, não é amplamente utilizado. Medidas devem ser tomadas para estimular seu uso como prática rotineira no atendimento de gestantes com risco de parto prematuro.

OBJECTIVE: To conduct a literature review on the use of antenatal corticosteroids for the prevention of peri-intraventricular hemorrhage. DATA SOURCE: Bibliography search in Pubmed and SciELO databases covering the past 20 years using the following key-words: "cerebral hemorrhage", "steroids" and "newborn infant". DATA SYNTHESIS: The peri-intraventricular hemorrhage is an important disease of preterm infants, especially those with less than 34 weeks, due to its serious neurological sequelae. Once the bleeding occurs, there is no specific treatment. Thus, prevention becomes the main goal of the research. Meta-analysis of randomized studies showed that antenatal corticosteroids reduce mortality and the incidence of hyaline membrane disease and peri-intraventricular hemorrhage. The physiologic basis for this protective effect in reducing the risk of peri-intraventricular hemorrhage is not completely clear. Besides accelerating lung maturity, antenatal steroids stimulate the maturation of the microvasculature of the germinal matrix, promote the thickening of the basement membrane, accelerate the formation of protein in tight functions and stabilize the cerebral blood flow. They also improve the birth conditions of preterm babies. CONCLUSIONS: The use of antenatal corticosteroids associated with implementing best practices to assist preterm infants reduces the frequency of peri-intraventricular hemorrhage. Despite its proven efficacy and safety, it is not widely used. Measures should be taken to encourage its use as a routine practice in the care of pregnant women at risk of premature birth.

Predisposing factors and outcome of stroke in childhood.

This prospective study was done to determine the predisposing factors and outcome of stroke in Bangladeshi children. It was carried out in Khulna Medical College Hospital from July 2002 to June 2007. Admitted children with acute neurological deficit attributable to a vascular cause were included in the study. Forty two children were finally diagnosed with stroke; 73.8% were male. Apart from paresis/paralysis in 35 (83.3%) cases, headache/vomiting/convulsion was the presenting problem in 28 (66.7%) cases at the onset. Infection in 17 (40.5%) children and trauma in 11 (26.2%) were the important predisposing factors. CT scan revealed ischemia and hemorrhage in 18 (42.8%) and 8 (19.1%) cases, respectively. Twenty two (52.4%) of the children recovered fully and 3 (7.2%) expired.

Hemorragia intracerebral espontánea / Spontaneous intracerebral hemorrhage

Se conoce que la hemorragia intraparenquimatosa es una afección frecuentemente grave y se asocia a elevada mortalidad. Se afirma que menos del 30 por ciento de los enfermos sobreviven 5 años después del ictus inicial y pocos recuperan su total independencia funcional. Se realizó una revisión sobre los factores de riesgo, la fisiopatología y los problemas frecuentes implicados en el tratamiento médico. Se halló que, según los resultados del estudio prospectivo STICH, la cirugía no ha demostrado beneficios superiores al tratamiento médico.

It is known that intraparenchymatous hemorrhage is a frequently severe affection and that it is associated with an elevated mortality. It is asserted that less than 30 percent of the sick survive 5 years after the initial stroke and a few recovered their total functional independence. A review was made on the risk factors, the physiopathology and the common problems involved in the medical treatment. According to the results of the STICH prospective study, surgery has not showed better benefits than the medical treatment.

Cerebral microbleeds and intravenous thrombolysis: case report / Micro-hemorragias cerebrais e trombólise endovenosa: relato de caso

Intravenous thrombolysis is an important procedure that has significant impact on ischemic stroke prognosis. However, intracranial hemorrhage (ICH) is a feared complication of this procedure. It has been suggested that cerebral microbleeds (CMBs) may increase the risk of ICH after thrombolysis. We report on a 69 years-old woman with multiple CMBs submitted to intravenous thrombolysis without complications.

A trombólise endovenosa é um procedimento importante que tem impacto significativo sobre o prognóstico de pacientes com acidente vascular cerebral isquêmico. Contudo, a hemorragia intracraniana (HIC) é complicação temida deste procedimento. Foi sugerido que micro-hemorragias cerebrais (MHC) aumentem o risco de HIC após trombólise. Relatamos o caso de mulher de 69 anos com múltiplas MHCs submetida a trombólise endovenosa sem complicações.

Early recombinant factor VIIa therapy in acute intracerebral hemorrhage: promising approach.

Intracerebral hemorrhage (ICH) is the most devastating form of stroke with a high morbidity and mortality. ICH constitutes about 20-30% of all strokes, with the prevalence being higher in Asian population. Treatment of ICH is predominantly conservative, which includes control of blood pressure, use of anti-cerebral edema measures such as mannitol and mechanical ventilation. The benefit of early surgery in ICH is debatable. Initial hematoma volume and subsequent growth in its size are important predictors of a poor outcome in ICH. This means that therapies aimed at preventing hematoma enlargement in the earliest possible window period could lead to a better outcome in ICH. Recombinant factor VIIa (rFVIIa) is one such agent, which has been shown to prevent hematoma expansion and improve outcome in acute ICH. The purpose of the current review is to focus on the evidence regarding the usefulness of rFVIIa in acute ICH.

Tratamento da hemorragia intraventricular com infusäo de estreptoquinase / Treatment of intraventricular hemorrhage with streptokinase infusion

Em estudo prospectivo realizado no Hospital de Base do Distrito Federal, 23 casos de pacientes com hemorragia intraventricular, de variadas etiologias, foram estudados e divididos em 3 grupos: Grupo I - Tratamento conservador ou grupo controle; Grupo II - Drenagem ventricular externa; Grupo III - Drenagem ventricular externa com infusao intraventricular de estreptoquinase. Todos os pacientes foram submetidos à tomografia computadorizada do crânio e analisados pela escala de Graeb, e foram pontuados através da escala de coma de Glasgow. Foi feita correlaçao entre os resultados obtidos com os 3 tipos de tratamento e chegou-se à conclusao de que, principalmente nos casos de hemorragia ventricular maciça, a infusao de estreptoquinase intraventricular proporcionou resultados melhores do que naqueles pacientes nos quais se adotou a conduta conservadora ou se procedeu a drenagem ventricular simples (grupos I e II, respectivamente).

Informe de un caso de hemorragia intraventricular espontánea en un recién nacido a término

Se informa de un caso de un recién nacido con hemorragia intraventricular, a quien se le confirmó con estudios neuroradiológicos, hemorragia de los plexos coroides, sin que se pudiera demostrar factores de riesgo asociados a este evento.