Predictors of post stroke cognitive impairment: VITATOPS cognition substudy.

INTRODUCTION: Post stroke cognitive impairment (PSCI) is a common complication of ischemic stroke. PSCI can involve different depending on clinical and stroke related characteristics. The aim of this study is to determine the factors associated with impairments in specific cognitive domains. METHODS: The Vitamins to Prevent Stroke (VITATOPS) trial is a large, multinational randomised controlled trial. In this substudy, consecutive patients admitted for ischaemic stroke or transient ischaemic attack (TIA) at a tertiary hospital in Singapore were included. PSCI was defined as impairment of any of the six cognitive subgroups - visuoconstruction, attention, verbal memory, language, visual memory and visuomotor function - that were assessed annually for up to five years. Univariate and multivariate Cox proportional hazard models were used to determine factors associated with impairments in each of these cognitive domains. RESULTS: A total of 736 patients were included in this study, of which 173 (23.5 %) developed cognitive impairment. Out of the six cognitive domains, the greatest proportion of patients had an impairment in visuoconstruction (26.4 %) followed by attention (19.8 %), verbal memory (18.3 %), language (17.5 %), visual memory (17.3 %) and visuomotor function (14.8 %). Patients with posterior circulation cerebral infarction (POCI) as the index stroke subtype had higher rates of cognitive impairment. Further subgroup analyses show that Indian race and advanced age were predictive of language impairment, whilst fewer years of education and POCI were predictive of verbal memory impairment. POCI was predictive of visual memory impairment, and advanced age and POCI were predictive of visuomotor function impairment. CONCLUSION: We identified visuoconstruction and attention domains to be the most affected in our Asian cohort of PSCI. Advanced age, lower levels of education, posterior circulation strokes and concomitant comorbidities such as peripheral artery disease are independent predictors of PSCI.

Bilateral effect of acupuncture on cerebrum and cerebellum in ischaemic stroke patients with hemiparesis: a randomised clinical and neuroimaging trial.

BACKGROUND: Acupuncture involving the limb region may be effective for stroke rehabilitation clinically, but the visualised and explanatory evidence is limited. Our objectives were to assess the specific effects of acupuncture for ischaemic stroke (IS) patients with hemiparesis and investigate its therapy-driven modification in functional connectivity. METHODS: IS patients were randomly assigned (2:1) to receive 10 sessions of hand-foot 12 needles acupuncture (HA, n=30) or non-acupoint (NA) acupuncture (n=16), enrolling gender-matched and age-matched healthy controls (HCs, n=34). The clinical outcomes were the improved Fugl-Meyer Assessment scores including upper and lower extremity (ΔFM, ΔFM-UE, ΔFM-LE). The neuroimaging outcome was voxel-mirrored homotopic connectivity (VMHC). Static and dynamic functional connectivity (sFC, DFC) analyses were used to study the neuroplasticity reorganisation. RESULTS: 46 ISs (mean(SD) age, 59.37 (11.36) years) and 34 HCs (mean(SD) age, 52.88 (9.69) years) were included in the per-protocol analysis of clinical and neuroimaging. In clinical, ΔFM scores were 5.00 in HA group and 2.50 in NA group, with a dual correlation between ΔFM and ΔVMHC (angular: r=0.696, p=0.000; cerebellum: r=-0.716, p=0.000) fitting the linear regression model (R2=0.828). In neuroimaging, ISs demonstrated decreased VMHC in bilateral postcentral gyrus and cerebellum (Gaussian random field, GRF corrected, voxel p<0.001, cluster p<0.05), which fitted the logistic regression model (AUC=0.8413, accuracy=0.7500). Following acupuncture, VMHC in bilateral superior frontal gyrus orbital part was increased with cerebro-cerebellar changes, involving higher sFC between ipsilesional superior frontal gyrus orbital part and the contralesional orbitofrontal cortex as well as cerebellum (GRF corrected, voxel p<0.001, cluster p<0.05). The coefficient of variation of VMHC was decreased in bilateral posterior cingulate gyrus (PPC) locally (GRF corrected, voxel p<0.001, cluster p<0.05), with integration states transforming into segregation states overall (p<0.05). There was no acupuncture-related adverse event. CONCLUSIONS: The randomised clinical and neuroimaging trial demonstrated acupuncture could promote the motor recovery and modified cerebro-cerebellar VMHC via bilateral static and dynamic reorganisations for IS patients with hemiparesis.

Comparative safety of tenecteplase vs alteplase for acute ischemic stroke.

INTRODUCTION: Tenecteplase has been compared to alteplase in acute stroke randomized trials, with similar outcomes and safety measures, but higher doses of tenecteplase have been associated with higher hemorrhage rates in some studies. Limited data are available on the safety of tenecteplase outside of clinical trials. METHODS: We examined the safety measures of intracranial hemorrhage, angioedema, and serious extracranial adverse events in a 21-hospital integrated healthcare system that switched from alteplase (0.9 mg/kg, maximum dose 90 mg) to tenecteplase (0.25 mg/kg, maximum dose 25 mg) for acute ischemic stroke. RESULTS: Among 3,689 subjects, no significant differences were seen between tenecteplase and alteplase in the rate of intracranial hemorrhage (ICH), parenchymal hemorrhage, or volume of parenchymal hemorrhage. Symptomatic hemorrhage (sICH) was not different between the two agents: sICH by NINDS criteria was 2.0 % for alteplase vs 2.3 % for tenecteplase (P = 0.57), and sICH by SITS criteria was 0.8 % vs 1.1 % (P = 0.39). Adjusted logistic regression models also showed no differences between tenecteplase and alteplase: the odds ratio for tenecteplase (vs alteplase) modeling sICH by NINDS criteria was 0.9 (95 % CI 0.33 - 2.46, P = 0.83) and the odds ratio for tenecteplase modeling sICH by SITS criteria was 1.12 (95 % CI 0.25 - 5.07, P = 0.89). Rates of angioedema and serious extracranial adverse events were low and did not differ between tenecteplase and alteplase. Elapsed door-to-needle times showed a small improvement after the switch to tenecteplase (51.8 % treated in under 30 min with tenecteplase vs 43.5 % with alteplase, P < 0.001). CONCLUSION: In use outside of clinical trials, complication rates are similar between tenecteplase and alteplase. In the context of a stroke telemedicine program, the rates of hemorrhage observed with either agent were lower than expected based on prior trials and registry data. The more easily prepared tenecteplase was associated with a lower door-to-needle time.

Prevalence and predictors of low folate levels among stroke survivors in a country without mandatory folate food fortification: Analysis of a Ghanaian sample.

BACKGROUND: While additional folic acid (FA) treatment has a neutral effect on lowering overall vascular risk in countries that mandate FA fortification of food, meta-analytic data suggest that folate supplementation reduces stroke risk in certain patient subgroups, and among people living in countries without mandatory folate food fortification. However, the burden of folate deficiency among adults with stroke in the world's poorest continent is unknown. PURPOSE: To assess the prevalence and predictors of folate deficiency among recent ischemic stroke survivors. METHODS: We analyzed data among consecutively encountered ischemic stroke patients aged ≥18 years at a tertiary medical center in Kumasi, Ghana between 10/2020 - 08/2021. We identified a modest sample of stroke free adults to serve as a comparator group. Fasting serum folate was measured using a radioimmunoassay and a cut-off of 4ng/mL used to define folate deficiency. Factors associated with serum folate concentration were assessed using a multilinear regression model. RESULTS: Comparing stroke cases (n = 116) with stroke-free comparators (n = 20), mean folate concentration was lower among stroke cases (7 ng/ml vs. 10.2 ng/ml, p = 0.004). Frequency of folate deficiency was higher among stroke cases vs. stroke-free controls (31% vs 5%, p = 0.02). Male sex (beta coefficient of -2.6 (95% CI: -4.2, -0.9) and LDL (ß: -0.76; -1.4, -0.07) were significantly associated with serum folate concentration. CONCLUSION: Almost one in three ischemic stroke survivors have folate deficiency potentially accentuating their risk for further adverse atherosclerotic events in a setting without folate fortification. A clinical trial of folate supplementation among stroke survivors is warranted.

Association between polycythemia and risk of ischemic stroke in males based on the national health insurance service-health screening cohort.

BACKGROUND: Polycythemia, a state in which the hematocrit or hemoglobin (Hb) concentration in the peripheral blood increases, is associated with several thrombosis-related diseases, of which cerebral infarction is relatively common. This study aimed to investigate the association between ischemic stroke and polycythemia, as a potential risk factor. RESEARCH DESIGN AND METHODS: This study included men who had undergone national health checkups between 2002 and 2003; the data were extracted from the Korean National Health Insurance Service-Health Screening database. The primary outcome was the risk ischemic stroke; adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for ischemic stroke were calculated using Cox proportional hazards regression models. RESULTS: In total, 207,737 male participants aged 40-79 years were included in this study. At the baseline, 13972 (6.7%) participants met the polycythemia criteria (Hb >16.5 g/dL). During the study period, 897 and 12,440 cases of ischemic stroke occurred in the polycythemia and normocythemia (13.0 g/dL ≤ Hb ≤16.5 g/dL) groups, respectively. Compared with the normocythemia group, the polycythemia group showed an adjusted HR (95% CI) for ischemic stroke of 1.12 (1.04-1.20). CONCLUSIONS: The risk of ischemic stroke was higher in participants with polycythemia than in those with normocythemia.

Identification and validation of platelet-related diagnostic markers and potential drug screening in ischemic stroke by integrating comprehensive bioinformatics analysis and machine learning.

Background: Ischemic stroke (IS), caused by blood and oxygen deprivation due to cerebral thrombosis, has links to activated and aggregated platelets. Discovering platelet-related biomarkers, developing diagnostic models, and screening antiplatelet drugs are crucial for IS diagnosis and treatment. Methods and results: Combining and normalizing GSE16561 and GSE22255 datasets identified 1,753 upregulated and 1,187 downregulated genes. Fifty-one genes in the platelet-related module were isolated using weighted gene co-expression network analysis (WGCNA) and other analyses, including 50 upregulated and one downregulated gene. Subsequent enrichment and network analyses resulted in 25 platelet-associated genes and six diagnostic markers for a risk assessment model. This model's area under the ROC curve outperformed single genes, and in the peripheral blood of the high-risk group, immune infiltration indicated a higher proportion of CD4, resting CD4 memory, and activated CD4 memory T cells, along with a lower proportion of CD8 T cells in comparison to the low-risk group. Utilizing the gene expression matrix and the CMap database, we identified two potential drugs for IS. Finally, a rat MACO/R model was used to validate the diagnostic markers' expression and the drugs' predicted anticoagulant effects. Conclusion: We identified six IS platelet-related biomarkers (APP, THBS1, F13A1, SRC, PPBP, and VCL) for a robust diagnostic model. The drugs alpha-linolenic acid and ciprofibrate have potential antiplatelet effects in IS. This study advances early IS diagnosis and treatment.

Do Concentration or Activity of Selenoproteins Change in Acute Stroke Patients? A Systematic Review and Meta-Analyses.

INTRODUCTION: Stroke is characterized by deleterious oxidative stress. Selenoprotein enzymes are essential endogenous antioxidants, and detailed insight into their role after stroke could define new therapeutic treatments. This systematic review aimed to elucidate how blood selenoprotein concentration and activity change in the acute phase of stroke. METHODS: We searched PubMed, EMBASE, and Medline databases for studies measuring serial blood selenoprotein concentration or activity in acute stroke patients or in stroke patients compared to non-stroke controls. Meta-analyses of studies stratified by the type of stroke, blood compartment, and type of selenoprotein measurement were conducted. RESULTS: Eighteen studies and data from 941 stroke patients and 708 non-stroke controls were included in this review. Glutathione peroxidase (GPx) was the only identified selenoprotein, and its activity was most frequently measured. Results from 12 studies and 693 patients showed that compared to non-stroke controls in acute ischaemic stroke patients, the GPx activity increased in haemolysate (standardized mean difference [SMD]: 0.27, 95% CI: 0.07-0.47) but decreased in plasma (mean difference [MD]: -1.08 U/L, 95% CI: -1.94 to -0.22) and serum (SMD: -0.54, 95% CI: -0.91 to -0.17). From 4 identified studies in 106 acute haemorrhagic stroke patients, the GPx activity decreased in haemolysate (SMD: -0.40, 95% CI: -0.68 to -0.13) and remained unchanged in plasma (MD: -0.10 U/L, 95% CI: -0.81 to 0.61) and serum (MD: -5.00 U/mL, 95% CI: -36.17 to 26.17) compared to non-stroke controls. Results from studies assessing the GPx activity in the haemolysate compartment were inconsistent and characterized by high heterogeneity. CONCLUSIONS: Our results suggest a reduction of the blood GPx activity in acute ischaemic stroke patients, a lack of evidence regarding a role for GPx in haemorrhagic stroke patients, and insufficient evidence for other selenoproteins.

Pacientes atendidos com suspeita de acidente vascular encefálico: análise de associação entre diagnóstico e desfecho clínico / Patients treated with suspected stroke: analysis of the association between diagnosis and clinical outcome / Pacientes tratados con sospecha de accidente cerebrovascular: análisis de la asociación entre diagnóstico y evolución clínica

Objetivo: verificar a associação entre o diagnóstico e desfechos clínicos em casos suspeitos de Acidente Vascular Encefálico, atendidos no pronto-socorro de um hospital de alta complexidade. Método: estudo transversal e observacional, com dados secundários e abordagem quantitativa, realizado sobre atendimentos de pacientes com suspeita de Acidente Vascular Encefálico isquêmico ou hemorrágico durante seis meses. Resultados: do total de 50 atendimentos, observou-se que entre os diagnósticos de Acidente Vascular Encefálico, destacaram-se o isquêmico com 18 casos (36%) e o hemorrágico com cinco (10%), sendo que este representou a maior proporção de óbitos, com o total de três (6%). Dentro da amostra, 24 (48%) não tiveram confirmação de AVE, sem qualquer ocorrência de óbito (p-valor= 0,001). Conclusão: observou-se na amostra a associação entre o diagnóstico de Acidente Vascular Encefálico e seu desfecho clínico, com a alta hospitalar como principal desfecho, porém com um alto percentual de óbitos.

Objective: to verify the association between diagnosis and clinical outcomes in suspected cases of stroke treated in the emergency room of a high complexity hospital. Method: a cross-sectional and observational study, with secondary data and a quantitative approach, carried out on visits to patients with suspected ischemic or hemorrhagic stroke for six months. Results: from the total of 50 consultations, it was observed that among the diagnoses of stroke, the ischemic one with 18 cases (36%) and the hemorrhagic one with five (10%) stood out, and this represented the largest proportion of cases. deaths, with a total of three (6%). Within the sample, 24 (48%) had no confirmation of stroke, without any occurrence of death (p-value= 0.001). Conclusion: an association between the diagnosis of stroke and its clinical outcome was observed in the sample, with hospital discharge as the main outcome, but with a high percentage of deaths.

Objetivo: verificar la asociación entre el diagnóstico y los resultados clínicos en casos sospechosos de Accidente cerebrovascular atendidos en el servicio de urgencias de un hospital de alta complejidad. Método: estudio transversal y observacional, con datos secundarios y abordaje cuantitativo, realizado en visitas a pacientes con sospecha de ictus isquémico o hemorrágico durante seis meses. Resultados: del total de 50 consultas, se observó que entre los diagnósticos de Accidente cerebrovascular se destacó el isquémico con 18 casos (36%) y el hemorrágico con cinco (10%), representando la mayor proporción de casos defunciones, con un total de tres (6%). Dentro de la muestra, 24 (48%) no tuvieron confirmación de diagnóstico, sin ocurrencia de muerte (p-valor= 0,001). Conclusión: se observó en la muestra una asociación entre el diagnóstico de Accidente cerebrovascular y su desenlace clínico, siendo el alta hospitalaria el principal desenlace, pero con un alto porcentaje de óbitos.

Neuromuscular Electric Stimulation in Addition to Exercise Therapy in Patients with Lower Extremity Paresis Due to Acute Ischemic Stroke. A proof-of-concept randomised controlled trial.

INTRODUCTION: Exercise therapy and neuromuscular electrical stimulation (NMES) during the initial 14 days after stroke may benefit recovery of gait. We aimed to determine whether poststroke NMES of vastus medial and tibial muscles during exercise therapy is more effective than exercise therapy alone. MATERIALS AND METHODS: In this proof-of-concept randomised trial patients with first-ever acute ischemic stroke and a leg paresis (40-85 years of age) were randomised (1:1) to 10 min of daily NMES + exercise therapy or exercise therapy alone. Primary outcome was the between-group difference in change in 6 min Walk Test (6MWT) at 90 days post stroke estimated with a mixed regression model. Secondary outcomes included 10 m Walk Test, Fugl-Meyer Motor Assessment, Guralnik Timed Standing Balance, Sit to Stand, Timed Up and Go, EQ-5D-5L, Montreal Cognitive Assessment and Becks Depression Inventory. RESULTS: 50 stroke survivors (25 in each group) with a mean age of 67 years (range 43-83) were included. An insignificant between-group difference in change of 28.3 m (95%CI -16.0 to 72.6, p = 0.23, adjusted for baseline) in 6MWT at 90-days follow-up was found, in favour of the NMES group. All secondary outcomes showed no statistically significant between-group difference. The conclusion was that adding NMES to exercise therapy had no effect on poststroke walking distance measured by the 6 MWT or any of the secondary outcomes. CONCLUSIONS: In this proof-of-concept RCT, we demonstrated that NMES in addition to exercise therapy during the first 14 days after onset of ischemic stroke did not improve walking distance or any of the secondary outcomes. Future studies with a longer trial period, stratifying patients into subgroups with comparable patterns of expected spontaneous recovery - if possible within 48 h post stroke, and greater sample size, than in this study are suggestions of how rehabilitation research could go on exploring the potential for NMES as an amplifier in stroke recovery.

Telestroke Across the Continuum of Care: Lessons from the COVID-19 Pandemic.

While use of telemedicine to guide emergent treatment of ischemic stroke is well established, the COVID-19 pandemic motivated the rapid expansion of care via telemedicine to provide consistent care while reducing patient and provider exposure and preserving personal protective equipment. Temporary changes in re-imbursement, inclusion of home office and patient home environments, and increased access to telehealth technologies by patients, health care staff and health care facilities were key to provide an environment for creative and consistent high-quality stroke care. The continuum of care via telestroke has broadened to include prehospital, inter-facility and intra-facility hospital-based services, stroke telerehabilitation, and ambulatory telestroke. However, disparities in technology access remain a challenge. Preservation of reimbursement and the reduction of regulatory burden that was initiated during the public health emergency will be necessary to maintain expanded patient access to the full complement of telestroke services. Here we outline many of these initiatives and discuss potential opportunities for optimal use of technology in stroke care through and beyond the pandemic.

The "Flying Intervention Team": A Novel Stroke Care Concept for Rural Areas.

BACKGROUND: Endovascular treatment of large vessel occlusion in acute ischemic stroke patients is difficult to establish in remote areas, and time dependency of treatment effect increases the urge to develop health care concepts for this population. SUMMARY: Current strategies include direct transportation of patients to a comprehensive stroke center (CSC) ("mothership model") or transportation to the nearest primary stroke center (PSC) and secondary transfer to the CSC ("drip-and-ship model"). Both have disadvantages. We propose the model "flying intervention team." Patients will be transported to the nearest PSC; if telemedically identified as eligible for thrombectomy, an intervention team will be acutely transported via helicopter to the PSC and endovascular treatment will be performed on site. Patients stay at the PSC for further stroke unit care. This model was implemented at a telestroke network in Germany. Fifteen remote hospitals participated in the project, covering 14,000 km2 and a population of 2 million. All have well established telemedically supported stroke units, an angiography suite, and a helicopter pad. Processes were defined individually for each hospital and training sessions were implemented for all stroke teams. An exclusive project helicopter was installed to be available from 8 a.m. to 10 p.m. during 26 weeks per year. Key Messages: The model of the flying intervention team is likely to reduce time delays since processes will be performed in parallel, rather than consecutively, and since it is quicker to move a medical team rather than a patient. This project is currently under evaluation (clinicaltrials NCT04270513).

Effect of Rhythm of Music Therapy on Gait in Patients with Stroke.

AIM: This study aims to analyze the effects of rhythm of music therapy on gait in patients with ischemic stroke, and explore the value of music therapy in walking training in stroke. METHODS: The present study is a prospective clinical study. Sixty patients with ischemic stroke, who were admitted to our hospital from October 2017 to December 2018, were enrolled. These patients were divided into two groups, according to the method of the random number table, with thirty patients in each group: control group and study group. Patients in the control group received conventional drug therapy, rehabilitation training and walking training, while the patients in the study group were given music therapy on the basis of the above mentioned therapies for four weeks, during which Sunday was regarded as a rest day, and the music therapy was suspended. The main outcome measures included indexes in evaluating the walking ability of patients in these two groups. At each time point, the Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS) and stroke rehabilitation treatment satisfaction questionnaire were used. RESULTS: The results revealed that the stride length, cadence and maximum velocity were higher in patients in the study group, when compared to patients in the control group, at the second week and end of the therapy, and the difference in step length between the affected side and healthy side was significantly lower in the study group than in the control group. These differences were statistically significant (P < 0.05). In the second week of therapy and at the end of therapy, the FMA and BBS scores were higher in the study group than in the control group, and the difference was statistically significant (P < 0.05). The total satisfaction rate was higher in the study group than in the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Under the stimulation of music rhythm, applying music therapy to patients with ischemic stroke can improve their gait, walking ability, lower limb motor function, balance ability and treatment satisfaction.

Lack of Racial, Ethnic, and Sex Disparities in Ischemic Stroke Care Metrics within a Tele-Stroke Network.

INTRODUCTION: Differences in access to stroke care and compliance with standard of care stroke management among patients of varying racial and ethnic backgrounds and sex are well-characterized. However, little is known on the impact of telestroke in addressing disparities in acute ischemic stroke care. METHODS: We conducted a retrospective review of acute ischemic stroke patients evaluated over our 17-hospital telestroke network in Texas from 2015-2018. Patients were described as Non-Hispanic White (NHW) male or female, Non-Hispanic Black (NHB) male or female, or Hispanic (HIS) male or female. We compared frequency of tPA and mechanical thrombectomy (MT) utilization, door-to-consultation times, door-to-tPA times, and time-to-transfer for patients who went on to MT evaluation at the hub after having been screened for suspected large vessel occlusion at the spoke. RESULTS: Among 3873 patients (including 1146 NHW male (30%) and 1134 NHW female (29%), 405 NHB male (10%) and 491 NHB female (13%), and 358 HIS male (9%) and 339 HIS female (9%) patients), we did not find any differences in door-to consultation time, door-to-tPA time, time-to-transfer, frequency of tPA administration, or incidence of MT utilization. CONCLUSION: We did not find racial, ethnic, and sex disparities in ischemic stroke care metrics within our telestroke network. In order to fully understand how telestroke alleviates disparities in stroke care, collaboration among networks is needed to formulate a multicenter telestroke database similar to the Get-With-The Guidelines.

Earlier Acupuncture Enhancing Long-Term Effects on Motor Dysfunction in Acute Ischemic Stroke: Retrospective Cohort Study.

Stroke is the leading fatal disease in China. This retrospective study aimed to explore the optimal acupuncture intervention time for long-term efficacy on motor dysfunction in patients suffering from acute ischemic stroke through 1-year of follow-up. Three hundred and nine patients collected at Longhua Hospital from January 2016 to December 2017 were classified into 3 groups based on the acupuncture intervention time, including groups A (within 2 days), B (within 3-7 days) and C (within 8-14 days). All patients had received standard treatment combined with acupuncture therapy. Specifically, acupuncture was performed at the acupoints including LI4 (Hegu), ST40 (Fenglong), DU20 (Baihui), and motor area of the scalp, followed by 2 electroacupuncture protocols based on different muscle tensions once a day for 5 days consecutively. The time-effect relationship was assessed using both the Fugl-Meyer Assessment (FMA) and the modified Barthel index (MBI) on the 90th day and 1st year, respectively. Meanwhile, the modified Rankin scale (mRS), high-sensitivity C-reactive protein (hs-CRP), and fibrinogen (FIB) were also measured during the 1-year follow-up. The favorable outcome rate was 74.4%. One-way univariate analysis of variance (ANOVA) revealed significant differences in FMA and MBI on the 90th day among the 3 groups ([Formula: see text] < 0.05), while no significant differences were observed in FMA, MBI or mRS at the 1st year between groups A and B. The levels of hs-CRP and FIB ([Formula: see text] < 0.05) were markedly reduced. Binary logistic regression analysis suggested that patients with atrial fibrillation (AF) (odds ratio (OR): 3.156), chronic kidney disease (CKD) (OR: 2.563), diabetes mellitus (DM) (OR: 2.174) or stroke history (OR: 1.883) were more inclined to recover poorly from nerve function deficit ([Formula: see text] < 0.05). Earlier acupuncture intervention may have a better long-term effect on motor dysfunction and inflammation during the 1-year follow-up. Moreover, acupuncture within 2 days is probably the optimal treatment time for early recovery on the 90th day.

Growth differentiation factor-11 supplementation improves survival and promotes recovery after ischemic stroke in aged mice.

Growth differentiation factor (GDF) 11 levels decline with aging. The age-related loss of GDF 11 has been implicated in the pathogenesis of a variety of age-related diseases. GDF11 supplementation reversed cardiac hypertrophy, bone loss, and pulmonary dysfunction in old mice, suggesting that GDF11 has a rejuvenating effect. Less is known about the potential of GDF11 to improve recovery after an acute injury, such as stroke, in aged mice. GDF11/8 levels were assessed in young and aged male mice and in postmortem human brain samples. Aged mice were subjected to a transient middle cerebral artery occlusion (MCAo). Five days after MCAo, mice received and bromodeoxyuridine / 5-Bromo-2'-deoxyuridine (BrdU) and either recombinant GDF11 or vehicle for five days and were assessed for recovery for one month following stroke. MRI was used to determine cerebrospinal fluid (CSF) volume, corpus callosum (CC) area, and brain atrophy at 30 days post-stroke. Immunohistochemistry was used to assess gliosis, neurogenesis, angiogenesis and synaptic density. Lower GDF11/8 levels were found with age in both mice and humans (p<0.05). GDF11 supplementation reduced mortality and improved sensorimotor deficits after stroke. Treatment also reduced brain atrophy and gliosis, increased angiogenesis, improved white matter integrity, and reduced inflammation after stroke. GDF11 may have a role in brain repair after ischemic injury.

Chip-based serum proteomics approach to reveal the potential protein markers in the sub-acute stroke patients receiving the treatment of Ginkgo Diterpene Lactone Meglumine Injection.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. is a kind of traditional Chinese medicinal material with a long history. Its main active ingredients, ginkgolides, can be used for the treatment of stroke and other cardio-cerebrovascular diseases. Ginkgo Diterpene Lactone Meglumine Injection (GDLI), a modernized TCM, has attracted much attention because of its neuroprotective and anti-inflammatory properties. AIM OF THE STUDY: To uncover the effects of GDLI on ischemic stroke patients, as well as the underlying biomarkers involved in sub-acute stroke. MATERIALS AND METHODS: We used a state-of-the-art targeted proteomics chip to investigate the association between numerous serum proteins (1101 proteins) and the sub-acute phase post-ischemic stroke. Then, the relative proteins of anti-apoptosis, anticoagulant, and neuroprotection of GDLI were verified in animal models. RESULTS: Compared with the serum from healthy volunteers, we identified 15 up-regulated proteins and 26 down-regulated proteins (FC ≥ 1.5) involved in inflammatory response, immune response, and nervous system development in the sub-acute ischemic stroke. The pro-inflammatory proteins, such as IL17, MSP-R, G-CSF-R, TLR3, MIP-3ß, TNFRSF19, and TNFRSF12, were significantly increased in serum, illustrating that the chronic inflammatory state was evident in the sub-acute stage of ischemic stroke. However, the common pro-inflammatory proteins, such as IL-1ß, IL-6, IL-8, TNF-α, IFN-γ, and IL-10, known to be up-regulated in acute stroke, had close or lightly lower levels than healthy humans (FC ≥ 1.5, P > 0.05). And some cytokines (IL3, CCL13, TNFRSF3, IL10 R beta, HLA-A, IL-1 F8/FIL1 eta, TNFRSF8, CCL18) were also markedly down-regulated in the sub-acute phase of stroke. These proteins are highly associated with the onset of stroke-induced immunosuppression and post-stroke infection. Moreover, we noticed that Ginkgo Diterpene Lactone Meglumine Injection (GDLI) treatment for 14 days was helpful to the recovery of patients in the subacute period. After the treatment of GDLI, it was observed that several inflammatory cytokines (i.e. IL-17 and IL-28A), chemokine (i.e. CCL14), and Coagulation Factor III were reduced. Meanwhile, the anti-inflammatory cytokines (IL-10 R alpha, GREMLIN, and Activin C) and neurotrophic factors (Neurturin and IGFBP2) were found to be up-regulated in stroke patients through self-control observation. Finally, we identified the IGFBP2 as a novel marker in the animal models. CONCLUSIONS: In summary, the potential markers in sub-acute stroke patients were highly different from known protein markers in the acute phase of ischemic stroke. The serum protein IGFBP2 could be novel biomarkers for the treatment of GDLI in sub-acute stroke patients. Our present findings provide an innovative insight into the novel treatment of GDLI in ischemic stroke therapy.

Acute Ischaemic Stroke Cooperation Group of Endovascular Treatment (ANGEL) registry: study protocol for a prospective, multicentre registry in China.

Background and purpose: Endovascular treatment could improve functional outcomes and reduce mortality in patients with intracranial large artery occlusion. This registry aims to evaluate the endovascular treatment delivery and to improve endovascular treatment algorithm in clinical practice for patients with stroke in China. Methods and analysis: This multicentric, nationwide, prospective registry plans to include 20 stroke centres and recruit 900 consecutive AIS patients with large-artery occlusion under endovascular treatment. This registry will enrol acute large vessel occlusion patients suitable for endovascular treatment and the inclusion and exclusion criteria. In this study, 90 days functional independence (modified Rankin Scale score ≤2) is the primary efficacy endpoint. The procedural efficacy endpoint of this registry is target artery recanalisation defined by modified Thrombolysis in Cerebral Infarction score 2b or 3 after endovascular therapy. Symptomatic intracranial haemorrhage with 24±3 hours after the procedure is the primary safety endpoint of this registry. Ethics and dissemination: Beijing Tiantan Hospital's Ethics committee and all other participating centres approved the protocol and data collection of Acute Ischaemic Stroke Cooperation Group of Endovascular Treatment registry. Each participant or representative had a written informed consent.

Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic stroke: a randomised controlled trial.

Purpose: To evaluate the efficacy and safety of Ginkgo biloba extract (GBE) in acute ischaemic stroke and its impact on the recurrence of vascular events. Methods: We conducted a multicentre, prospective, randomised, open label, blinded, controlled clinical trial enrollingpatients with an onset of acute stroke within 7 days from five hospitals in China Jiangsu Province. Participants were assigned to the GBE group (450 mg GBE with 100 mg aspirin daily) or the control group (100 mg aspirin daily) for 6 months. The primary outcome was the decline in the Montreal Cognitive Assessment score at 6 months. Secondary outcomes were other neuropsychological tests of cognitive and neurological function, the the incidence of adverse events and vascular events. Results: 348 patients were enrolled: 179 in the GBE group and 169 in the control group. With 18 patients lost to follow-up, the dropout rate was 5.17%. Admission data between two groups were similar, but in the GBE group there was a marked slow down in the decline in the Montreal Cognitive Assessment scores (-2.77±0.21 vs -1.99±0.23, P=0.0116 (30 days); -3.34±0.24 vs -2.48±0.26, P=0.0165 (90 days); -4.00±0.26 vs -2.71±0.26, P=0.0004 (180 days)) compared with controls. The National Institutes of Health Stroke Scale scores at 12 and 30 days, the modified Rankin Scale scores for independent rate at 30, 90 and 180 days, and the Barthel Index scores at 30, 90 and 180 days in the GBE group were significantly improved compared with controls. Improvements were also observedin GBE groups for Mini-Metal State Examination scores of 30, 90 and 180 days, Webster's digit symbol test scores at 30 days and Executive Dysfunction Index scores at 30 and 180 days. No significant differences were seen in the incidence of adverse events or vascular events. Conclusions: We conclude that GBE in combination with aspirin treatment alleviated cognitive and neurological deficits after acute ischaemic stroke without increasing the incidence of vascular events. Trial registration number: ChiCTR-TRC-12002688.