Treatment Of Ischemic Stroke Patients Research Articles

The Roles of RhoA/ROCK/NF-κB Pathway in Microglia Polarization Following Ischemic Stroke.

Ischemic stroke is the leading cause of death and disability worldwide. Nevertheless, there still lacks the effective therapies for ischemic stroke. Microglia are resident macrophages of the central nervous system (CNS) and can initiate immune responses and monitor the microenvironment. Microglia are activated and polarize into proinflammatory or anti‑inflammatory phenotype in response to various brain injuries, including ischemic stroke. Proinflammatory microglia could generate immunomodulatory mediators, containing cytokines and chemokines, these mediators are closely associated with secondary brain damage following ischemic stroke. On the contrary, anti-inflammatory microglia facilitate recovery following stroke. Regulating the activation and the function of microglia is crucial in exploring the novel treatments for ischemic stroke patients. Accumulating studies have revealed that RhoA/ROCK pathway and NF-κB are famous modulators in the process of microglia activation and polarization. Inhibiting these key modulators can promote the polarization of microglia to anti-inflammatory phenotype. In this review, we aimed to provide a comprehensive overview on the role of RhoA/ROCK pathway and NF-κB in the microglia activation and polarization, reveal the relationship between RhoA/ROCK pathway and NF-κB in the pathological process of ischemic stroke. In addition, we likewise discussed the drug modulators targeting microglia polarization.

A comprehensive review for artificial intelligence on neuroimaging in rehabilitation of ischemic stroke.

Stroke is the second leading cause of death worldwide, with ischemic stroke accounting for a significant proportion of morbidity and mortality among stroke patients. Ischemic stroke often causes disability and cognitive impairment in patients, which seriously affects the quality of life of patients. Therefore, how to predict the recovery of patients can provide support for clinical intervention in advance and improve the enthusiasm of patients for rehabilitation treatment. With the popularization of imaging technology, the diagnosis and treatment of ischemic stroke patients are often accompanied by a large number of imaging data. Through machine learning and Deep Learning, information from imaging data can be used more effectively. In this review, we discuss recent advances in neuroimaging, machine learning, and Deep Learning in the rehabilitation of ischemic stroke.

Efficacy and safety of stem cells in the treatment of ischemic stroke: A meta-analysis.

Stem cell therapy on ischemic stroke has long been studied using animal experiments. The efficacy and safety of this treatment in ischemic stroke patients remain uncertain. We searched for all clinical randomized controlled trials published before October 2023, on PubMed, EMBASE, and the Cochrane Library using predetermined search terms, and performed a meta-analysis of the efficacy of stem cell therapy in ischemic stroke patients. 13 studies that included 592 ischemic stroke patients were reviewed. The mRS (MD -0.32, 95% CI -0.64 to 0.00, I2 = 63%, P = .05), NIHSS (MD -1.63, 95% CI -2.69 to -0.57, I2 = 58%, P = .003), and BI (MD 14.22, 95% CI 3.95-24.48, I2 = 43%, P = .007) showed effective stem cell therapy. The mortality (OR 0.42, 95% CI 0.23-0.79, I2 = 0%, P = .007) showed improved prognosis and reduce mortality with stem cell therapy. Stem cell therapy reduces mortality and improves the neurological prognosis of ischemic stroke patients. However, due to the different types of stem cells used and the limited data in the reported studies, the safety of clinical applications of stem cells in patients with ischemic stroke must be carefully evaluated. Future randomized controlled trials with large sample sizes from controlled cell sources are warranted to validate this finding.

Investigation of the Effectiveness of Doxycycline on the Improvement of Oxidative Stress Biomarkers in Patients with Ischemic Stroke

Background and Objective: Considering the role of oxidative stress in the pathogenesis of ischemic stroke, antioxidant and anti-inflammatory drugs can be a potential treatment in these patients. This study aimed to investigate the effectiveness of doxycycline on the improvement of oxidative stress biomarkers in patients with ischemic stroke. Materials and Methods: This clinical trial study was performed on 48 patients with ischemic stroke who had referred to Besat Hospital in Hamadan, Iran, in 2023. They were randomly and equally assigned to the intervention (doxycycline at the rate of 100 mg every 12 hours) and placebo groups for one week. Before and after the intervention, serum levels of malondialdehyde (MDA), glutathione (GSH), total oxidant status, total antioxidant capacity, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were measured. Results: The study groups had no statistically significant difference in all measured biomarkers in the first 24 h after the stroke (P>0.05). In both study groups, the biomarkers of MDA and total oxidant status decreased after treatment. This decrease was greater in the intervention group, compared to the placebo group with a statistically significant difference. The total antioxidant capacity and GSH increased in both groups, and this increase was more significant in the intervention group, compared to the placebo group. In both groups, serum levels of CRP and ESR decreased, but no statistically significant difference was observed between the two groups. Conclusion: Addition of doxycycline to the standard treatment of ischemic stroke patients may reduce oxidative stress biomarkers; however, to confirm the results of this study, studies with a larger sample size are needed.

Abstract WP299: Encephalomyosynangiosis Promotes Mature Angiogenesis After Ischemic Stroke

Backgrounds: Current treatments for ischemic stroke patients is ineffective. The brain's inherent ability to self-heal post ischemic stroke is hampered by inadequate blood supply to the affected region. Encephalomyosynangiosis (EMS), a neurosurgical intervention, has proven successful in promoting angiogenesis in patients with Moyamoya disease. We have earlier shown that EMS can increase angiogenesis after stroke in the implanted region, it is not known if those blood vessels are stable or mature. Given that EMS provide balanced growth factors, we therefore hypothesized that EMS enhances stable or mature cerebral angiogenesis in the cortical region surrounding the muscle graft. Methods: Following a 60-minute period of transient middle cerebral artery occlusion (MCAo), mice were assigned randomly to either MCAo alone or MCAo followed by EMS (3-4 hours post MCAo).. Mice were sacrificed at 7, 21, or 70 days post MCAo. A mouse angiogenesis and proteomic profile array was employed to quantify the expression of angiogenic and neuromodulating proteins. Immunohistochemistry was utilized to visualize the bonding of the graft with the brain cortex, changes in vessel density, and pericyte coverage to assess the degree of normal or mature angiogenesis. Results and Conclusions: Preliminary data indicate successful graft implantation and a significantly increased vessel density (P<0.05 compared to the MCAo alone) in proximity to the muscle graft, signifying increased angiogenesis after stroke. EMS-treated mice exhibited an early improvement in sensory motor deficits post-stroke. Analysis of the angiogenesis and proteomic profile array data unveiled a downregulation of antiangiogenic factors (such as interleukin-10 and Fetuin A) and an upregulation of pro-angiogenic cytokines or growth factors (including Fibroblast Growth Factor and C-X-C Motif Chemokine 12) in the EMS group. Co-immunostaining of the endothelial cell marker (Lectin) with the pericyte marker Platelet-Derived Growth Factor Receptor Beta (PDGFRβ) after 70 days of EMS suggested the stability and maturity of new blood vessels. In summary, the EMS procedure appears effective, holding promise for enhanced stable angiogenesis which may help to expedite recovery following ischemic stroke.

Effect of the Bioactive Compound Curcumin on Conditions After Ischemic Stroke: A Systematic Review

Ischemic stroke is a common degenerative disease in Indonesia caused by interrupted or restricted blood supply to part of brain, preventing it from getting oxygen and nutrients. Without sufficient blood supply, brain cells begin to die. Various treatments for ischemic stroke patients have been developed and implemented, but are still ineffective in treating or preventing brain damage. Curcumin is one of the bioactive compounds which mostly found in turmeric which is one of the main spices resource in Indonesia that has many benefits as a medicine. People have been making use of curcumin as a medicine for various diseases, one of which is stroke. Therefore, this systematic review analysed qualitatively the effect of curcumin on the brain condition after ischemic stroke. The method used in this study was a systematic review of 8 databases in the last 10 years, from 2012 to August 2022. Study included was only experimental study on rats. Based on 19 articles gathered, there was a decrement in ROS, COX-2, iNOS, NF-kB, TNF-α, IL-6, Bax, Caspase-9, Caspase-3, ICAM-1, MMP-9, neurological deficit score, and an increment in BCL-2, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) in rats receiving curcumin intervention either orally or intravenously. Curcumin affects the ischemic brain in a number of ways, namely as an antioxidant, anti-inflammatory, anti-apoptotic, Blood-Brain-Barrier (BBB) protector, increasing neurogenesis, and reducing neurological deficits. It is concluded that curcumin has an elevating effect in protecting brain condition after an ischemic stroke.

Pharmacological Inhibition of NHE1 Protein Increases White Matter Resilience and Neurofunctional Recovery after Ischemic Stroke.

To date, recanalization interventions are the only available treatments for ischemic stroke patients; however, there are no effective therapies for reducing stroke-induced neuroinflammation. We recently reported that H+ extrusion protein Na+/H+ exchanger-1 (NHE1) plays an important role in stroke-induced inflammation and white matter injury. In this study, we tested the efficacy of two potent NHE1 inhibitors, HOE642 and Rimeporide, with a delayed administration regimen starting at 24 h post-stroke in adult C57BL/6J mice. Post-stroke HOE642 and Rimeporide treatments accelerated motor and cognitive function recovery without affecting the initial ischemic infarct, neuronal damage, or reactive astrogliosis. However, the delayed administration of NHE1 blockers after ischemic stroke significantly reduced microglial inflammatory activation while enhanced oligodendrogenesis and white matter myelination, with an increased proliferation and decreased apoptosis of the oligodendrocytes. Our findings suggest that NHE1 protein plays an important role in microglia-mediated inflammation and white matter damage. The pharmacological blockade of NHE1 protein activity reduced microglia inflammatory responses and enhanced oligodendrogenesis and white matter repair, leading to motor and cognitive function recovery after stroke. Our study reveals the potential of targeting NHE1 protein as a therapeutic strategy for ischemic stroke therapy.

“Lifting Yang to Dredging Du Meridian Manipulation” acupuncture alleviates cerebral ischemia-reperfusion injury by mediating the NF-κB pathway

BackgroundIschemic stroke is a permanent neurological impairment resulting from the narrowing or blockage of blood vessels in the brain. The effectiveness of “Lifting Yang to Dredging Du Meridian Manipulation” (LYDD) acupuncture in clinical treatment of ischemic stroke patients has been well-established. Nevertheless, its mechanism is still uncertain. MethodsMCAO/R rat models at different time points of reperfusion (24, 36, 48 and 72 h) were constructed, and LYDD acupuncture treatment was performed. Zea-Longa score and TTC staining were used for assessing neurological impairment and cerebral infarct in rats, respectively. The pathological changes of cerebral tissue in each group were observed by HE and Nissl's staining. Cerebral tissue from each group was subjected to RNA-seq, and differentially expressed genes (DEGs) were performed for GO and KEGG enrichment analysis, and hub gene was identified based on the String database and MCODE algorithm. ResultsLYDD acupuncture treatment significantly reduced Zea-Longa score, dry-wet weight ratio, infarct area, inflammatory factor levels (IL-1β and TNF-α), cerebral lesions, number of Nissl body and neuronal apoptosis in the MCAO/R model at different time points of reperfusion. A total of 3518 DEGs were identified in the MCAO/R model compared to the control group, and 3461 DEGs were present in the treatment group compared to the MCAO/R model, and they may be implicated in neurotransmitter transmission, synaptic membrane potential, cell junctions, inflammatory response, immune response, cell cycle, and ECM. The expression trends of BIRC3, LTBR, PLCG2, TLR4 and TRADD mRNAs in the Hub gene were consistent with the RNA-seq results, and LYDD acupuncture treatment significantly inhibited MCAO/R-induced p65 nuclear translocation. ConclusionsLYDD acupuncture ameliorates cerebral ischemia-reperfusion injury by inhibiting NF-κB pathway activity.

Cost-effectiveness of tenecteplase versus alteplase for stroke thrombolysis evaluation trial in the ambulance.

Tenecteplase administered to patients with ischaemic stroke in a mobile stroke unit (MSU) has been shown to reduce the perfusion lesion volumes and result in ultra-early recovery. We now seek to assess the cost-effectiveness of tenecteplase in the MSU. A within-trial (TASTE-A) economic analysis and a model-based long-term cost-effectiveness analysis were performed. This post hoc within-trial economic analysis utilised the patient-level data (intention to treat, ITT) prospectively collected over the trial to calculate the difference in both healthcare costs and quality-adjusted life years (QALYs, estimated from modified Rankin scale score). A Markov microsimulation model was developed to simulate the long-term costs and benefits. In total, there were 104 patients with ischaemic stroke randomised to tenecteplase (n = 55) or alteplase (n = 49) treatment groups, respectively in the TASTE-A trial. The ITT-based analysis showed that treatment with tenecteplase was associated with non-signficantly lower costs (A$28,903 vs A$40,150 (p = 0.056)) and greater benefits (0.171 vs 0.158 (p = 0.457)) than that for the alteplase group over the first 90 days post the index stroke. The long-term model showed that tenecteplase led to greater savings in costs (-A$18,610) and more health benefits (0.47 QALY or 0.31 LY gains). Tenecteplase-treated patients had reduced costs for rehospitalisation (-A$1464), nursing home care (-A$16,767) and nonmedical care (-A$620) per patient. Treatment of ischaemic stroke patients with tenecteplase appeared to be cost-effective and improve QALYs in the MSU setting based on Phase II data. The reduced total cost from tenecteplase was driven by savings from acute hospitalisation and reduce need for nursing home care.

Identifying stroke diagnosis-related features from medical imaging reports to improve clinical decision-making support

BackgroundMedical imaging reports play an important role in communication of diagnostic information between radiologists and clinicians. Head magnetic resonance imaging (MRI) reports can provide evidence that is widely used in the diagnosis and treatment of ischaemic stroke. The high-signal regions of diffusion-weighted imaging (DWI) images in MRI reports are key evidence. Correctly identifying high-signal regions of DWI images is helpful for the treatment of ischaemic stroke patients. Since most of the multiple signals recorded in head MRI reports appear in the same part, it is challenging to identify high-signal regions of DWI images from MRI reports.MethodsWe developed a deep learning model to automatically identify high-signal regions of DWI images from head MRI reports. We proposed a fine-grained entity typing model based on machine reading comprehension that transformed the traditional two-step fine-grained entity typing task into a question-answering task.ResultsTo prove the validity of the model proposed, we compared it with the fine-grained entity typing model, of which the F1 measure was 5.9% and 3.2% higher than the F1 measures of the models based on LSTM and BERT, respectively.ConclusionIn this study, we explore the automatic identification of high-signal regions of DWI images from the description part of a head MRI report. We transformed the identification of high-signal regions of DWI images to an FET task and proposed an MRC-FET model. Compared with the traditional two-step FET method, the model we proposed not only simplifies the task but also has better performance. The comparable result shows that the work in this study can contribute to improving the clinical decision support system.

Circulating Extracellular Vesicles in Stroke Patients Treated With Mesenchymal Stem Cells: A Biomarker Analysis of a Randomized Trial.

Mesenchymal stem cells (MSCs) secrete trophic factors and extracellular vesicles (EVs). However, the level and role of EVs after MSC therapy in patients with stroke are unknown. We investigated whether circulating EVs and trophic factors are increased after MSCs and are related to the therapeutic benefits in the STARTING-2 trial (Stem Cell Application Researches and Trials in Neurology-2) participants. In this prospective randomized controlled trial, patients with chronic major stroke were assigned, in a 2:1 ratio, to receive autologous MSC intravenous injection (MSC group, n=39) or standard treatment (control group, n=15) and followed for 3 months. Detailed clinical assessment and neuroplasticity on diffusion tensor image and resting-state functional magnetic resonance imaging were evaluated. Serial samples were collected, before/after MSCs therapy. The primary outcome measure was circulating factors that are associated with the clinical improvement in the Fugl-Meyer Assessment (secondary end point of the trial) and neuroplasticity on diffusion tensor image and resting-state functional magnetic resonance imaging. Additional outcome measures were microRNAs and trophic factors enriched in the plasma EVs, obtained using quantitative polymerase chain reaction and ELISA, respectively. Circulating EV levels were increased ≈5-fold (mean±SD, from 2.7×109±2.2×109 to 1.3×1010±1.7×1010 EVs/mL) within 24 hours after injection of MSCs (P=0.001). After adjustment of age, sex, baseline stroke severity, and the time interval from stroke onset to treatment, only the EV number was independently associated with improvement in motor function (odds ratio, 5.718 for EV numberLog [95% CI, 1.144-28.589]; P=0.034). Diffusion tensor image and resting-state functional magnetic resonance imaging showed that integrity of the ipsilesional corticospinal tract and intrahemispheric motor network were significantly correlated with circulating EV levels, respectively (P<0.05). MicroRNAs related to neurogenesis/neuroplasticity (eg, microRNA-18a-5p) were significantly increased in circulating EVs after MSC therapy (P=0.0479). In contrast, trophic factor levels were not changed after MSC therapy. This trial is the first to show that treatment of ischemic stroke patients with MSCs significantly increases circulating EVs, which were significantly correlated with improvement in motor function and magnetic resonance imaging indices of plasticity. URL: https://www. gov; Unique identifier: NCT01716481.

Abstract WMP119: Tanshinone IIa-loaded Nanoparticles And Induced Pluripotent Stem Cell-derived Neural Stem Cell Therapies Enhance Recovery In A Translational Pig Ischemic Stroke Model

Induced pluripotent stem cell-derived neural stem cells (iNSCs) have led to cellular and functional recovery in ischemic stroke models. However, the therapeutic effects of iNSC treatment are limited by decreased cell survival in the cytotoxic stroke environment. Tanshinone IIA is a potential anti-inflammatory and antioxidative treatment that may modulate this harsh microenvironment and lead to improved iNSC survival in stroke tissue. To test this hypothesis, the combined effects of Tanshinone IIA-loaded nanoparticles (Tan IIA-NPs) and iNSCs were evaluated in a translational pig ischemic stroke model. 18 Yucatan pigs underwent middle cerebral artery occlusion and were assigned to the following treatment groups: PBS+PBS, PBS+iNSC, or Tan IIA-NP+iNSC. PBS or Tan IIA-NPs were administered intracisternally 1-hour post-stroke and either PBS or iNSCs were transcranially transplanted into the parenchyma 5 days post-stroke. Magnetic resonance imaging (MRI) was collected 24 hours post-stroke and 12 weeks post-transplantation. Immunohistochemistry was completed 12 weeks post-iNSC transplantation. MRI demonstrated that Tan IIA-NPs significantly reduced lesion volumes, midline shift, and intracerebral hemorrhage, while iNSCs improved white matter integrity. Immunohistochemistry revealed that Tan IIA-NP+iNSC treatment significantly increased NeuN+ neurons in the penumbra relative to PBS+iNSC and PBS+PBS treatment groups. Tan IIA-NP+iNSC treated pigs also showed significantly decreased Iba1+ immune cells and GFAP+ activated astrocytes in the penumbra relative to PBS+iNSC and PBS+PBS treated pigs. Tan IIA-NP+iNSC treated pigs showed significantly increased DCX+ neuroblasts at the lesion border and in the ventricular lining of the subventricular zone relative to PBS+iNSC and PBS+PBS pigs. In addition, PBS+iNSC treated pigs also showed significantly more DCX+ neuroblasts than PBS+PBS pigs. Collectively, Tan IIA-NPs in combination with iNSCs possess potential as a multifaceted neuroprotective and regenerative treatment for ischemic stroke patients. The robust tissue preservation and recovery responses in a predictive large animal model strongly support the continued evaluation of this novel combination therapy.

Using Multiple Logistic Regression to Determine Factors Affecting Delaying Hospital Arrival of Patients with Acute Ischemic Stroke.

Early treatment of ischemic stroke patients who arrive at the hospital ≤4.5 hours after the onset of symptoms with recombinant tissue plasminogen activator is more beneficial and very important. This study is aimed to investigate the factors delaying the hospital arrival of patients with acute ischemic stroke by using multiple logistic regression analysis. This descriptive cross-sectional study was done on patients diagnosed with acute ischemic stroke who were referred to Ardabil city Training and Research hospital at 2018. All patients and/or patient relatives were interviewed and data were collected through a checklist including demographic and clinical data of patients to explore the involved factors delaying hospital arrival of patients and then analyzed using multiple logistic regression analysis. Of all included patients, only 25.3% arrived at the hospital in ≤ 4.5 hours. By using multivariate logistic regression analysis, living in cities (P = 0.007), cigarette consumption (P = 0.032), having valvular heart disease (P = 0.008), and gender (P = 0.049) were factors associated with an early arrival to the hospital. Results showed that most of the patients had a considerable delay in arriving at the hospital in ≤ 4.5 hours. Thus, providing health promotion strategies to improve society awareness of early symptoms of stroke, training of local physicians about the importance of early arrival of stroke patients, and more extended ambulance services in all cities and rural areas are necessary for better management of acute stroke patients in this area.

PENGARUH PEMBERIAN SUPLEMEN IKAN GABUS PADA STATUS NEUROLOGIS PASIEN STROKE ISKEMIK DI RUMAH SAKIT UMUM DAERAH PATUH PATUT PATJU

Stroke is the leading cause of death and disability in a world that requires treatment and care in the long term. Many factors that influence the outcome and the level of worsening after ischemic stroke include hypoalbumin which is one of the factors affecting the outcome of stroke. This study to determine the effect of supplementation of Snakehead fish on neurological improvement ischemic stroke patients at Patuh Patut Patju hospital.&#x0D; This study included quasi experimental research with Sparate Samples Pretest-Posttest design, Pre treatment ischemic stroke patients who have not given supplements of Snakehead fish (H1) and post treatment of ischemic stroke patients who have been given supplement Snakehead fish dose 3 times a day for 14 day (H14). Clinical outcome in grades of serum albumin levels, NIHSS and Barthel index. Analysis outcome with SPSS Shapiro wilk test, Wilcoxon signed test , and Mann whitney testOutcome post treatment decrease NIHSS score (p = 0,000, &lt;0,05), increased Barthel index score (p = 0,000, &lt;0,05), increased serum albumin level (p = 0.000, &lt;0,05). Snakehead fish supplement can decrease NIHSS score, increase barthel index score and serum albumin level post given for 14 day.

The Clinical Efficacy of Clopidogrel Bisulfate Tablets Combined with Olmesartan Medoxomil for Ischemic Stroke with Hypertension and the Effect of Angiotensin II Type 1 Receptor Level on Prognosis.

Background Ischemic stroke combined with hypertension can increase risks of stroke recurrence and death. Aim The aim of this study is to investigate the clinical efficacy of clopidogrel bisulfate tablets combined with olmesartan medoxomil in the treatment of ischemic stroke patients with hypertension and the effect of angiotensin II type 1 receptor (AT1R) level on prognosis. Methods Ninety ischemic stroke patients with hypertension were chosen for continuous treatment with clopidogrel bisulfate tablets and olmesartan medoxomil for 12 months. The Modified Edinburgh Scandinavian Stroke Scale (MESSS) score, Brunnstrom score, Barthel score, death, recurrence, and progression of cerebrovascular residual lesions were observed and recorded during the treatment period. According to the plasma AT1R expression of the patients before treatment, the patients were divided into a high-AT1R group and low-AT1R group. Then, survival analysis was performed. Results Compared with pretreatment, the MESSS scores of the patients at the first, second, third, sixth, ninth, and twelfth months after treatment were reduced (p < 0.01) while the Brunnstrom score and Barthel score were prominently boosted (p < 0.01). Compared with the low-AT1R group, patients in the high-AT1R group had higher rates of stroke recurrence and progression of residual cerebrovascular lesions (p < 0.05). Conclusion Clopidogrel bisulfate tablets combined with olmesartan medoxomil has prominent clinical effects in the treatment of ischemic stroke patients with hypertension, evidently improving the prognosis. In addition, the level of AT1R may be a vital factor affecting the prognosis.

Thrombectomy is a cost-saving procedure up to 24h after onset.

The treatment of ischemic stroke due to large-vessel occlusion has been revolutionized by mechanical thrombectomy (MT), as multiple trials have consistently shown improved functional outcomes compared to standard medical management both in the early and late time windows after symptom onset. However, MT is an interventional procedure that is more costly than best supportive care (BSC). We set out to study the cost-utility and budget impact of MT + BSC versus BSC alone for large-vessel occlusion using a combined decision tree and Markov model. The analysis was conducted from a Belgian payer perspective over a lifetime horizon, and health states were defined by the modified Rankin Scale (mRS). The treatment effect of MT + BSC combined clinical outcomes from all published early and late treatment window studies showing improved mRS after 90days. Resource use and utilities were informed by an observational Belgian study of 569 stroke patients. Long-term mRS transitions were sourced from the Oxford Vascular study. MT + BSC generated 1.31 additional quality-adjusted life years and resulted in cost savings of €10,216 per patient over lifetime. Deterministic sensitivity analyses demonstrated dominance of MT over a wide range of parameter inputs. In a Belgian setting, adding MT to BSC within an early time window for 1575 eligible stroke patients every year produced cost savings between €6.3 million (year 1) and €14.6 million (year 5), or a total cost saving of €56.2 million over 5years. Mechanical thrombectomy is a highly cost-effective treatment for ischemic stroke patients, providing quality-adjusted survival at lower health care cost, both when given in an early time window, as well as in a late time window.

SLC17A3 rs9379800 and Ischemic Stroke Susceptibility at the Northern Region of Malaysia

ObjectivesThe relationships of Paired Like Homeodomain 2 (PITX2), Ninjurin 2 (NINJ2), TWIST-Related Protein 1 (TWIST1), Ras Interacting Protein 1 (Rasip1), Solute Carrier Family 17 Member 3 (SLC17A3), Methylmalonyl Co-A Mutase (MUT) and Fer3 Like BHLH Transcription Factor (FERD3L) polymorphisms and gene expression with ischemic stroke have yet to be determined in Malaysia. Hence, this study aimed to explore the associations of single nucleotide polymorphisms (SNPs) and gene expression with ischemic stroke risk among population who resided at the Northern region of Malaysia. Materials and methodsStudy subjects including 216 ischemic stroke patients and 203 healthy controls were recruited upon obtaining ethical clearance. SNP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism assays. Gene expression levels were quantified by real-time polymerase chain reaction assays. Statistical and genetic analyses were conducted with SPSS version 22.2, PLINK version 1.07 and multifactor dimensionality reduction software. ResultsStudy subjects with G allele, CG or GG genotypes of SLC17A3 rs9379800 demonstrated increased risk of ischemic stroke with the odds ratios ranging from 1.76-fold to 3.14-fold (p<0.05). When stratified study subjects according to the ethnicity, SLC17A3 rs9379800 G allele and CG genotype contributed to 2.14- and 2.96-fold of ischemic stroke risk among Malay population significantly, in the multivariate analysis (p<0.05). However, no significant associations were observed for PITX2, NINJ2, TWIST1, Rasip1, and MUT polymorphisms with ischemic stroke risk in the multivariate analysis for the pooled cases and controls as well as when stratified them according to the ethnicity. Lower mRNA expression levels of Rasip1, SLC17A3, MUT and FERD3L were observed among cases (p<0.05). After FDR adjustment, the mRNA level of SLC17A3 remained significantly associated with ischemic stroke among Malay population (q=0.034). ConclusionIn conclusion, this study suggests that SLC17A3 rs9379800 polymorphism and its gene expression contribute to significant ischemic stroke risk among Malaysian population, particularly the Malay who resided at the Northern Region of the country. Our findings can provide useful information for the future diagnosis, management and treatment of ischemic stroke patients.

Post-stroke treatment of storax improves long-term outcomes of stroke in rats

Ethnopharmacological relevanceThe lack of widely applicable pharmacological treatments for ischemic stroke patients has led to a growing interest in traditional medicine. The identification of pharmacologically active components of the clinically used traditional medicine has been considered translationally significant. SuHeXiang Wan is a prescription containing 15 herbs approved by Chinese National Drug Administration (CNDA) for treating ischemic stroke. Storax is one of the main contents in this prescription and is believed to play a significant pharmacological role, which has been used to treat stroke for nearly 1000 years in traditional Chinese medicine. Emerging experimental investigations suggested Storax might be effective for treating ischemic stroke. Aim of the studyThis study aimed to test our hypothesis that post-stroke treatment of Storax can improve long-term outcomes of stroke. Materials and methodsMale Wistar rats (250–280 g) subjected to 2 h of MCAO following reperfusion were treated with Storax by intragastric at 1 h and repeated at 3 h, 6 h after stroke. In the first set experiment, an array of neurological function deficits assessments were tested before and after stroke, brain lesion size was examined at 28 days after ischemia. CD31 and synatophysin were analyzed by immunohistochemistry. In the second set experiment, markers of proinflammatory activation were determined at 24 h after stroke. ELISA was performed to analyze brain concentrations of TNF-α, IL-1β and circulating levels of iNOS, ET-1, and immunohistochemistry was performed to determine GFAP, IBA-1 and NF-κB p65. ResultsStorax significantly alleviated neurological deficits from 7 days after stroke and lasted until 28 days, corresponding to the significantly decreased lesion volume at 28 days after stroke; Meanwhile, Storax increased the density of CD31and SYP in peri-infarct areas. At 24 h after stroke, Storax significantly inhibited brain TNF-α, IL-1β expression and circulating iNOS, ET-1 levels, reduced the NF-κB/p65 positive cell number, and decreased activated microglia/macrophages and astrocytes cell numbers alongside reversed their morphological transformations. ConclusionOur experimental findings demonstrate treatment of Storax at the acute phase significantly improves long-term neurological outcomes in the focal stroke model of rats. We also speculate that inhibition of acute proinflammation activation by Storax might be associated with its beneficial pharmacological effect, but remain to define and elucidate in future investigation.

CLINICAL EVALUATION OF FUNCTIONAL ELECTRICAL STIMULATION EFFECTIVENESS OF ANTAGONISTIC MUSCLE GROUPS AT WRIST AND ANKLE IN PATIENTS AFTER ISCHEMIC STROKE IN LONG TERM FOLLOW UP

Introduction So far, no detailed evaluation of the results of neuromuscular therapy with functional electrical stimulation combined with kinesiotherapy in long-term observation with clinical methods assessing the scale of post-stroke deficits, muscle strength and the severity of the spasticity symptom on the more paresis side has been performed. Aim The aim of this study was to compare results of neuromuscular functional electrical stimulation algorithm (NMFES) associated with a uniform system of kinesiotherapy based mainly on proprioceptive neuromuscular facilitation (PNF) procedures versus the same system of applied kinesiotherapy alone in home-based treatment of ischemic stroke patients in two months follow up. Material and methods The same set of clinical studies has been applied to a group of 25 healthy volunteers once as well as three times (T0- at hospital ward up to 7 days after an incident, T1- after 21 days of treatment at a hospital ward, T2-after 62 days of home-based treatment) to the 50 patients after ischemic stroke divided into two groups, 25 subjects each (NMFES+K and K groups). Evaluation of treatment effects in two groups of patients was performed with NIHSS scale, Lovett’s scale and Ashworth’s scale. Results After 60 days of applied treatment, only patients of the NMFES+K group represented a statistically significant decrease of NIHSS scale score, indicating the retirement of stroke symptoms. The symptom of increased muscle tension evaluated in the Ashwort’s scale in patients of the NMFES+K group significantly decreased but not in patients of K group. The muscle force of extensor muscles of upper and lower extremities significantly increased only in patients of the NMFES+K group. In general, patients from both groups did not present significant abnormalities in sensory perception within dermatomes C5-C7 and L5-S1 on the more paretic side. Conclusions The proposed personalized, safe and controlled in use a NMFES electrostimulation algorithm gives better, and long-lasting functional effects than previously used as a standard, making it a targeted treatment method. In patients after an ischemic stroke, this treatment reduces post-stroke deficits, increases muscle strength, and reduces the severity of the spasticity symptom on the more paralyzed side. Keywords: ischemic stroke, rehabilitation, functional neuromuscular stimulation, proprioceptive neuromuscular facilitation, clinical evaluation

Potential of dual-layer spectral CT for the differentiation between hemorrhage and iodinated contrast medium in the brain after endovascular treatment of ischemic stroke patients

BackgroundOne possible complication after mechanical thrombectomy is hemorrhage. In conventional CT it is often difficult to differ between extravasation of iodinated contrast medium and blood. This differentiation, however, is essential for treatments with anticoagulants and antiplatelets. PurposeTo evaluate dual-layer spectral Computed Tomography (DLSCT) for the differentiation between intracranial hemorrhage and iodinated contrast medium in ischemic stroke patients after mechanical thrombectomy. Materials and methodsFirst, in vitro experiments were performed. Then, head CT images of 47 patients after mechanical thrombectomy were analyzed. Virtual non-contrast (VNC) images and iodine density maps (IDM) were calculated and evaluated. Region of interests (ROIs) analyses were performed. Sensitivity and specificity as well as ROC curves were calculated. ResultsIDM and VNC images enabled clear differentiation between blood and iodine and reliable quantification of different iodine concentrations in vitro. A total of 23 hyperdense areas were detected in 13 patients, classified as hemorrhage (n = 7), iodinated contrast medium (n = 4) and a mixture of both (n = 12). Sensitivity and specificity for the detection of blood was 100%. ConclusionDLSCT enables differentiation between intracranial hemorrhage and iodinated contrast medium in patients after mechanical thrombectomy and might improve diagnostic imaging in post-interventional stroke patients.