BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Objective:To investigate the role and possible mechanism of edaravone dexborneol in the prevention and control of patho-logical injury of brain tissue around hematoma after intracerebral hemorrhage(ICH).Methods:A total of 176 Sprague-Dawley rats were randomly divided into sham-operation group,ICH group,edaravone group,and edaravone dexborneol group,with 44 rats in each group.All rats except those in the sham-operation group were used to establish a rat model of acute ICH,and each group was further di-vided into 1-day,3-day,7-day,and 14-day subgroups according to the time of evaluation,with 11 rats in each subgroup.At 2 hours after modeling,drugs were administered via intraperitoneal injection,i.e.,6 ml/kg normal saline for the sham-operation group and the ICH group,6 mg/kg edaravone for the edaravone group,and 7.5 mg/kg edaravone dexborneol for the edaravone dexborneol group,fol-lowed by subsequent administration every 12 hours until day 14.The modified Neurological Severity Score(mNSS)was used to assess neurological function;the wet-dry weight method was used to measure the water content of brain tissue;the biochemical methods were used to measure nitric oxide(NO)and total antioxidant capacity(T-AOC)in brain tissue around the hematoma;immunohistochemistry was used to measure the content of CD16 and CD206 in brain tissue around the hematoma.Results:The mNSS score on day 3(peak of the disease)was 0.6±0.5 for the sham-operation group,14.0±1.6 for the ICH group,9.8±0.8 for the edaravone group,and 10.4±1.1 for the edaravone dexborneol group,with a water content of 63.2±2.14,85.61±1.43,81.48±1.9,and 76.77±1.44,respectively,and the content of NO was 2.45±0.46,9.98±0.54,8.77±0.36,and 7.92±0.43,respectively;the content of T-AOC was 0.67±0.02,0.74±0.03,0.78±0.02,and 0.84±0.03,respectively;the content of CD16 was 143.8±15.82,3 673.81±166.33,2 970.74±132.75,and 2 521.69±140.74,respectively;the content of CD206 was 548.46±93.68,726±97.81,915.28±100.33,and 1 119.51±160.52,respectively.There were significant differences in these indica-tors between the edaravone dexborneol group and the other three groups(all P<0.05).Conclusion:Edaravone dexborneol can alleviate neurological deficit caused by ICH and exert a neuroprotective effect by reducing brain tissue edema around the hematoma,alleviating oxidative stress,and regulating the polarization of microglial cells.

Mechanical thrombectomy is the most effective method for the treatment of adult acute ischemic stroke caused by occlusion of large blood vessels. Compared with traditional therapy, the curative effect is greatly improved. The evidence-based medicine evidence of the treatment is sufficient, and the efficacy is safe and reliable. Since 2015, it has been recommended by the guidelines of various countries. In 2018, the time window of mechanical thrombectomy has been extended from six hours to 24 hours, which benefits more adult patients with acute ischemic stroke. However, due to the lack of high-quality clinical research, there is no corresponding guide recommendation in children, which greatly limits its clinical application. There are some cases of mechanical thrombectomy in children and a few retrospective studies show that it is safe and effective in children in the world, but there are also some challenges. The article reviewed the challenges and implementation plan of thrombectomy in children to provide reference for clinical practice.

Objective To analyze the clinical efficacy of acupuncture and moxibustion in treating acute cerebral infarction.Methods A thorough literature search of randomized and controlled tests of acupuncture and moxibustion in treating the acute cerebral infarction was conducted.A meta-analysis was performed using version 5.3 of the ReviewManager software.Results Thirty-nine reports covering 3792 cases were found and analyzed.The neurologic impairment analysis found that in the experimental group mean difference (MD) was-1.86,with the 95％ credibility interval (CI) of between-2.06 and-1.66 showing significant differences compared with the control group.The average clinical effectiveness rate of the experimental groups was 3.95,with a 95％ CI of between-3.02 and 5.16,significantly higher than the control groups'.The experimental groups' markedly effective rate was 1.54,with a 95％ CI of 1.40 to 1.70,showing significant differences compared with the control groups.Conclusion Acupuncture and moxibustion are effective in treating acute cerebral infarction.They are worth popularizing in clinical practice.

Objective To evaluate the curative effect of imipenem on stroke associated pneumonia(SAP).Methods Seventy-two inpatients with SAP in ICU of the Affiliated Hospital of Southwest Medical University from January 2014 to January 2016 were selected.The patients were given the stroke associated treatment and symptomatic treatment.On this basis imipenem 1.0 g+ 0.9％ normal saline 100 mL was injected,once per 8 h.The disease condition change during treatment process was observed.The laboratory test results and chest CT changes were compared between before and after 2-week treatment.And the correlation analysis of risk factors was performed.Results Twelve cases died during treatment,60 cases were survival.The body temperature was declined to normal at 2 weeks after using imipenem.The NIHSS score,white blood cell (WBC) count,neutrophil count and C-reactive protein level after treatment were decreased compared with before treatment,the blood gas analysis showed that the arterial partial pressure of oxygen and oxygenation index were elevated compared with before treatment.The chest CT showed that pulmonary inflammatory exudation lesions and hydrothorax were absorbed and improved compared with before treatment.Among 72 cases,55 cases were cured,5 cases were remarkably effective,12 cases were ineffective,the total effective rate was 83.3 ％.The risk factors correlation analysis indicated that swallowing dysfunction,consciousness disturbance and acute attack history of chronic obstructive pulmonary disease were negatively correlated with the curative effect.Conclusion Imipenem has satisfactory effect in treating SAP.

Objective To discuss the effects of Paclitaxel(PTX) on levels of CD28 and CTLA-4,B lymphocyte stimulator(BAFF) in experimental autoimmune encephalomyelitis(EAE).Methods The 50 rats were divided into 5 groups by the random number table, 10 rats in each group,the doses of small group,Middle group, High group were 1 mg/kg,2 mg/kg,4 mg/kg by intraperitoneal injection for 10 consecutive days, the normal group and model group were injected 0.9% NS 2 mL,Using brain tissue score to estimate the neurological dysfunctions of rats.Using flow cytometry to detect the levels of CD28 and CTLA-4,using enzyme-linked immunosorbent (ELISA) to detect the levels of BAFF.Results The brain tissue score in PTX experimental groups were lower than model group,the comparative differences between groups were statistically significant(P < 0.01);The levels of CD28 in PTX groups were lower than EAE group,the comparative differences between groups were statistically significant(P < 0.01).The levels of CTLA-4 in PTX groups were higher than EAE group,the comparative differences between groups were statistically significant(P < 0.01);the content of BAFF in all PTX groups were lower than EAE control group.Conclusions PTX could decrease the brain tissue score,the mechanism may adjust the express of CD28、CTLA-4 in brain and the expression of BAFF.PTX may have preventive and therapeutic effects on EAE rats.

Objective To investigate the effect of doxycycline on the Th1/Th2 cell balance in experimental allergic encepha-lomyelitis(EAE)rats.Methods Forty female Wistar rats were randomly divided into the EAE control group,low,medium and high does DOX treatment groups,10 cases in each group.The onset situation in rats was observed.The IL-4 and IFN-γlevels secreted by peripheral blood mononuclear cells (PBMC)at the peak stage were detected.The levels of IL-1β,IL-10,TNF-αin brain tissue,and the albumin content in cerebrospinal fluid and serum were detected.The QA value was calculated.Results In each DOX group,the clinical symptoms of rats were alleviated compared with the EAE control group.In each DOX group,the PBMC secreting IFN-γlev-el and IFN-γ/IL-4 ratio in the onset peak stage were lower than those in the EAE control group,while the IL-4 level was higher than that in the EAE control group(P <0.01).Compared with the medium-dose DOX group,the increase of IL-4 level in the high-dose DO group was unapparent(P >0.05),but the difference between other DOX groups had statistical significance(P <0.01).The IL-1βand TNF-αlevels of brain tissue and QA value during onset peak stage in various doses DOX groups were decreased compared with the EAE control group,while the IL-10 level was increased compared with the EAE control group(P <0.05).With the DOX dose increasing,the levels of IL-1β,TNF-αand QA value in various doses DOX groups became lower,the IL-10 level became high-er,there was statistically significant difference among various doses DOX groups (P <0.05 ).Conclusion DOX can obviously alle-viate the clinical symptoms of EAE rats,its mechanism may be related with that DOX could decrease the level of Th1 cytokine and increase the level of Th2 cytokine,correct the Th1/Th2 cell balance,thus protect the blood brain barrier(BBB).

Objective To explore the effects of vasoactive intestinal peptide (VIP)on the ratio of CD4+CD25+Treg/CD4+T cell and the expression of TGF-β1 in experimental autoimmune encephalomyelitis (EAE)rats. Methods We randomly divided 60 healthy female Wistar rats into normal control group,EAE control group,VIP low-dose group and VIP high-dose group.We used myelin basic protein (MBP)+ complete adjuvant (CFA)to establish EAE model. Since the day of model construction, the low- and high-dose VIP groups received intraperitoneal injection of 4 nmol/kg (0.2 mL)and 16 nmol/kg (0.8 mL)of VIP every other day,respectively;normal control group and EAE group received injection of saline of 0.8 mL for 10 days in a row.We recorded the peak of neurological dysfunction score (NDS)changes in the rats,observed the pathological changes and GFAP+astrocyte activation in the brain at the morbidity peak of rats with HE staining,and detected the ratio of CD4+CD25+Treg/CD4+T in the spleen with FACS and TGF-β1 cytokine level in brain tissue with ELISA.Results The peak nerve dysfunction score was decreased in each VIP dose group.In normal control group,there were decreased inflammatory cell infiltration and decreased number of active astrocytes in the brain tissue.The degree of infiltration of inflammatory cells and astrocyte activation in VIP control groups were significantly lower than those in EAE group.The CD4+CD25+Treg/CD4+T cell ratio of the spleen tissue in each dose VIP treated group rats was higher than that in EAE control group.The cytokine level of TGF-β1 in the brain tissue increased in each VIP dose group in the dose-dependent manner.Conclusion Through up-regulating the ratio of CD4+CD25+Treg/CD4+T cell in the spleen tissue,increasing TGF-β1 content in brain tissue,and inhibiting the infiltration of inflammatory cells and the astrocyte activation,VIP plays an important role in prevention and control of EAE.

Objective To explore the effect of vasoactive intestinal peptide (VIP) on the content of IL-17A in the brain tissue of rat models of experimental autoimmune encephalomyelitis ( EAE) .Methods Sixty healthy female Wistar rats were randomly divided into normal control group, EAE control group, low-dose VIP group and high-dose VIP group. Ten healthy guinea pigs were used to prepare anti-IL-17A antibody.Myelin basic protein ( MBP) +complete adjuvant ( CFA) were used to establish the EAE model.Since the first day of modelling, the low-dose and high-dose VIP groups received intraperitoneal injection of VIP 4 nmol/kg (0.2 mL) and 16 nmol/kg (0.8 mL), respectively, every other day for 10 consecutive days.The normal control group and EAE group were injected with 0.8 mL saline instead of VIP.The incubation period, progression and the peak of neurological dysfunction scores ( NDS) of the rats were recorded.The levels of IL-17A in the brain tissue was determined by ELISA assay, and the GFAP+astrocyte activation in brain at morbidity peak in the rats was examined using anti-GFAP ( glial fibrillary acidic protein) antibodies.Results The incubation period were extended, the progression period was shortened and the peak neuological dysfunction score ( NDS) was decreased in the VIP-treated groups, in a dose-response relationship.The cytokine levels of IL-17A and the astrocyte activation degree in brain tissue were reduced in each VIP dose group, in a dose-response relationship.Conclusions VIP exerts therapeutic effect on experimental autoimmune encephalomyelitis through lowering the IL-17A content and inhibition of astrocyte activation in the brain tissue.

OBJECTIVE:To study the protective effect of sivelestat sodium on experimental autoimmune encephalomyelitis (EAE) model rats. METHODS:60 Wistar rats were randomly divided into normal control group (normal saline),model group (normal saline),positive drug group [prednisone acetate tablets 5 mg/(kg·d)] and sivelestat sodium low-dose,middle-dose and high-dose groups [5,8,10 mg/(kg·d)] with 10 rats in each group. Except for normal control group,other groups were given guin-ea pig spinal cord homogenate as antigen to produce EAE model,and then given relevant medicine ip since the same day of model-ing,for consecutive 16 d. The neurologic function of mice was scored,and pathological changes of brain and spinal cord were ob-served;the content of IFN-γ,IL-4,CCL3,chemotactic factor CCL5 regulating and activating normal T cell expression and secre-tion were determined. RESULTS:Compared with normal control group,neurological function score and the content of IFN-γ, CCL5 and CCL3 increased,while IL-4 content decreased (P<0.01);myelinoclasis and inflammatory cell infiltration occurred. Compared with model group,neurological function score and the content of CCL3 and CCL5 decreased in positive drug group and sivelestat sodium low-concentration,medium-concentration and high-concentration groups (P<0.01);both myelinoclasis and in-flammatory cell infiltration relieved;the content of IFN-γdecreased,while IL-4 content increased in positive drug group and sivele-stat sodium high-concentration group;IL-4 content increased in sivelestat sodium medium-concentration group (P<0.01);there was no statistical significance in other groups(P>0.05). Above effect depended on drug dose. CONCLUSIONS:Sivelestat sodium can relieve myelinoclasis and inflammatory cell infiltration,and the mechanism may be related to the decrease of IFN-γ content, the increase of IL-4 content,and inhibition of CCL3 and CCL5 expression in peripheral blood.