Early antiplatelet therapy used for acute ischemic stroke and intracranial hemorrhage

In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical Cases.We evaluate their claims on the benefit of use of Aspirin in the early management of patients with ischemic stroke.We also comment on their contention of using aspirin in the early management of patients with intracranial hemorrhage,a practice not seen in modern medicine.Large clinical trials such as the International Stroke Trial and the Chinese Acute Stroke Trial have shown the benefit of Aspirin use within 48 h of patients with Acute Ischemic Stroke.The findings were corroborated in the open-label trial performed by Zhang et al in a smaller sample group of 25 patients where they showed improvement in functional scores at 90 days without an increase in adverse events.As such,this intervention is also recommended by the American Heart Association stroke guidelines from 2021.With regard to Intracranial hemorrhage,traditional practice has been to discontinue or avoid antiplatelet therapy in these patient groups.However,no studies have been done to evaluate this management strategy that is more borne out of the mechanism behind Aspirin’s effect on the coagulation pathway.Zhang et al evaluate the benefits of Aspirin on patients with low-volume intracranial hemorrhage,i.e.,less than 30 mL on computed tomo-graphy imaging,and show no increase in mortality.The caveat of this finding is that all outcomes were pooled into one group for results,and the number of patients was low.While more studies with larger patient groups are required,the data from Zhang et al suggests that patients with small-volume intracranial hemorrhages may benefit from Aspirin administration in the acute phase of management.

Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.

Stem cell-based ischemic stroke therapy:Novel modifications and clinical challenges

Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and paracrine abilities give hope for neuroprotection.Recent studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and pretreatment.Thesemethods improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic areas.However,many problems must be resolved before SC therapy can be clinically applied.These issues include production quality and quantity,stability during transportation and storage,as well as usage regulations.Herein,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy challenges.We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.

The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

Virtual Reality-Based Mirror Therapy for Upper Extremity Function among Stroke Patients:A Meta-analysis and Systematic Review

[Objectives]To investigate the evidence-based effect of virtual reality-based mirror therapy system(VR-MT)on upper extremity function among stroke patients.[Methods]A systematic electronic searching of the Medline,PubMed,Web of Science and CNKI was initially performed up to June 10,2024.The risk of bias of the included studies was evaluated using RevMan 5.4 software based on the Cochrane Handbook for Systematic Reviews.The random-effects model or fixed-effects models was employed to estimate the standardized mean difference(SMD).The subgroup analyses were conducted exploring theVR-MT type(immersive or non-immersive)and comparing with MT or control group.[Results]In total 8 studies with a total of 273 stroke patients were included in this review.The pooled analysis of these trials showed a statistically significant enhancement inFMA-UE scores(6 studies,SMD=0.72,[95%CI 0.37 to 1.06];P<0.0001,I^(2)=31%)and Box and Block Test(BBT)(3 studies,SMD=0.49,[95%C/0.05 to 0.93];P=0.03,I^(2)=0%),rather than Manual Function Test(MFT)scores(3 studies,SMD=0.38,[95%CI-0.09 to 0.84];P=0.11,I^(2)=0%)following the application of reality-based mirror therapy.Additionally,the subgroup analysis results indicated that immersive VR-MT can significantly improve FMA-UE(5studies,SMD=0.73,[95%CI 0.24 to 1.23];P=0.004,I^(2)=43%).In contrast,the overall effect of non-immersive VR-MT was non-significant(2 studies,SMD=0.33,[95%CI-0.69 to 1.34];P=0.53,I^(2)=72%).[Conclusions]In this systematic review and meta-analysis,our findings indicate that immersiveVR-MT has the potential to improve upper extremity function among stroke patients.

Effects of Acupuncture and Tuina Combined with Rehabilitation Therapy on Oxidative Stress Response and Motor Function in Stroke Hemiplegia Patients

Objective:To explore the effects of acupuncture and tuina combined with rehabilitation therapy on oxidative stress response and motor function in stroke hemiplegia patients.Methods:Sixty stroke hemiplegia patients were randomly divided into observation and control groups,with 30 cases each.The control group received conventional rehabilitation therapy,while the observation group also underwent acupuncture and tuina.After 8 weeks of treatment,oxidative stress indicators[malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)],neurological deficit scores(NIHSS),Fugl-Meyer motor function scores(FMA),and activities of daily living(Barthel Index)were compared between the two groups.Results:Before treatment,there were no significant differences in MDA,NIHSS scores,FMA scores,and Barthel Index between the two groups(P>0.05).After 8 weeks,the observation group had lower MDA and NIHSS scores,but higher SOD,GSH-Px,FMA scores,and Barthel Index compared to the control group,with statistically significant differences(P<0.05).Conclusion:Acupuncture and tuina combined with rehabilitation therapy can effectively improve oxidative stress levels,promote neurological recovery,enhance motor function,and improve daily living activities in stroke hemiplegia patients.This combined therapy is recommended for clinical application.

Comprehensive Rehabilitation Therapy of Traditional Chinese Medicine Combined with Modern Rehabilitation Training Improves the Spasticity and Motor Function of Hemiplegia after Stroke

Objective:To analyze the impact of comprehensive rehabilitation therapy of traditional Chinese medicine(TCM)(based on modern rehabilitation training)on the spasticity and motor function in stroke patients with hemiplegia.Methods:Seventy-nine stroke and hemiplegia patients admitted to the hospital from June 2021 to June 2023 were selected and randomly divided into a control group(39 cases)using modern rehabilitation training,and an observation group combined with comprehensive TCM rehabilitation therapy(40 cases),over 1 month.The clinical index data of the two groups were compared.Results:There were differences in the clinical index data between the two groups.The total effective rate after 2 treatment in the observation group(92.50%)was higher than that of the control group(74.36%)(χ^(2)=4.727,P<0.05).All central sensitization inventory(CSI)and stroke quality of life(PRO)scores in both groups were lower after treatment,with the observation group having lower scores as compared to the control group(P<0.05).The scores of FMA(upper limbs,lower limbs),Barthel index scores,and Functional Ambulation Categories(FAC)scores of both groups increased after treatment,with the observation group having higher scores as compared to the control group(P<0.05).Conclusion:Comprehensive TCM rehabilitation therapy had a significant therapeutic effect on patients with hemiplegia after stroke.It improved the patient’s spasticity,limb movement,and walking function.Their daily living abilities and quality of life were also enhanced.

Treatment of Post-stroke Dysphagia by VitalStim Therapy Coupled with Conventional Swallowing Training

To investigate the effects of VitalStim therapy coupled with conventional swallowing training on recovery of post-stroke dysphagia,a total of 120 patients with post-stroke dysphagia were randomly and evenly divided into three groups：conventional swallowing therapy group,VitalStim therapy group,and VitalStim therapy plus conventional swallowing therapy group.Prior to and after the treatment,signals of surface electromyography（sEMG） of swallowing muscles were detected,swallowing function was evaluated by using the Standardized Swallowing Assessment（SSA） and Videofluoroscopic Swallowing Study（VFSS） tests,and swallowing-related quality of life（SWAL-QOL） was evaluated using the SWAL-QOL questionnaire.There were significant differences in sEMG value,SSA,VFSS,and SWAL-QOL scores in each group between prior to and after treatment.After 4-week treatment,sEMG value,SSA,VFSS and SWAL-QOL scores were significantly greater in the VitalStim therapy plus conventional swallowing training group than in the conventional swallowing training group and VitalStim therapy group,but no significant difference existed between conventional swallowing therapy group and VitalStim therapy group.It was concluded that VitalStim therapy coupled with conventional swallowing training was conducive to recovery of post-stroke dysphagia.

Constraint-induced movement therapy in treatment of acute and sub-acute stroke: a meta-analysis of 16 randomized controlled trials

OBJECTIVE： The aim of this meta-analysis was to evaluate the clinical efficacy of constraint-induced movement therapy in acute and sub-acute stroke. DATA SOURCES： The key words were stroke, cerebrovascular accident, constraint-induced therapy, forced use, and randomized controlled trial. The databases, including China National Knowledge Infrastructure, WanFang, Weipu Information Resources System, Chinese Biomedical Literature Database, PubMed, Med- line, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, were searched for studies on randomized controlled trials for treating acute or sub-acute stroke published before March 2016. DATA SELECTION： We retrieved relevant randomized controlled trials that compared constraint-induced movement therapy in treatment of acute or sub-acute stroke with traditional rehabilitation therapy （tradi- tional occupational therapy）. Patients were older than 18 years, had disease courses less than 6 months, and were evaluated with at least one upper extremity function scale. Study quality was evaluated, and data that met the criteria were extracted. Stata 11.0 software was used for the meta-analysis. OUTCOME MEASURES： Fugl-Meyer motor assessment of the arm, the action research-arm test, a motor activity log for amount of use and quality of movement, the Wolf motor function test, and a modified Bar- thel index. RESULTS： A total of 16 prospective randomized controlled trials （379 patients in the constraint-induced movement-therapy group and 359 in the control group） met inclusion criteria. Analysis showed significant mean differences in favor of constraint-induced movement therapy for the Fugl-Meyer motor assessment of the arm （weighted mean difference （WMD） = 10.822; 95% confidence intervals （95% CI）： 7.419-14.226）, the action research-arm test （WMD = 10.718; 95% CI： 5.704-15.733）, the motor activity log for amount of use and quality of movement （WMD = 0.812; 95% CI： 0.331-1.293） and the modified Barthel index （WMD = 10.706; 95% CI： 4.417-16.966）. CONCLUSION： Constraint-induced movement therapy may be more beneficial than traditional rehabili- tation therapy for improving upper limb function after acute or sub-acute stroke.

Speech and language therapy for aphasia following subacute stroke

The aim of this study was to investigate the time window, duration and intensity of optimal speech and language therapy applied to aphasic patients with subacute stroke in our hospital. The study consisted of 33 patients being hospitalized for stroke rehabilitation in our hospital with first stroke but without previous history of speech and language therapy. Sixteen sessions of impairment-based speech and language therapy were applied to the patients, 30-60 minutes per day, 2 days a week, for 8 successive weeks. Aphasia assess- ment in stroke patients was performed with Giilhane Aphasia Test-2 before and after treatment. Compared with before treatment, fluency of speech, listening comprehension, reading comprehension, oral motor evaluation, automatic speech, repetition and naming were improved after treatment. This suggests that 16 seesions of speech and language therapy, 30-60 minutes per day, 2 days a week, for 8 successive weeks, are effective in the treatment of aphasic patients with subacute stroke.

Who benefits from percutaneous closure of patent foramen ovale vs medical therapy for stroke prevention? In-depth and updated metaanalysis of randomized trials

BACKGROUND A few randomized clinical trials(RCT) and their meta-analyses have found patent foramen ovale closure(PFOC) to be beneficial in prevention of stroke compared to medical therapy. Whether the benefit is extended across all groups of patients remains unclear.AIM To evaluate the efficacy and safety of PFOC vs medical therapy in different groups of patients presenting with stroke, we performed this meta-analysis of RCTs.METHODS Electronic search of PubMed, EMBASE, Cochrane Central, CINAHL and ProQuest Central and manual search were performed from inception through September 2018 for RCTs. Ischemic stroke(IS), transient ischemic attack(TIA), a composite of IS, TIA and systemic embolism(SE), mortality, major bleeding,atrial fibrillation(AF) and procedural complications were the major outcomes.Random-effects model was used to perform analyses.RESULTS Meta-analysis of 6 RCTs including 3560 patients showed that the PFOC,compared to medical therapy reduced the risk of IS [odds ratio: 0.34; 95%confidence interval: 0.15-0.78; P = 0.01] and the composite of IS, TIA and SE [0.55(0.32-0.93); P = 0.02] and increased the AF risk [4.79(2.35-9.77); P < 0.0001]. No statistical difference was observed in the risk of TIA [0.86(0.54-1.38); P = 0.54],mortality [0.74(0.28-1.93); P = 0.53] and major bleeding [0.81(0.42-1.56); P = 0.53]between two strategies. Subgroup analyses showed that compared to medical therapy, PFOC reduced the risk of stroke in persons who were males, ≤ 45 years of age and had large shunt or atrial septal aneurysm.CONCLUSION In certain groups of patients presenting with stroke, PFOC is beneficial in preventing future stroke compared to medical therapy.

Constraint-induced movement therapy promotes brain functional reorganization in stroke patients with hemiplegia

Stroke patients with hemiplegia exhibit flexor spasms in the upper limb and extensor spasms in the lower limb, and their movement patterns vary greatly. Constraint-induced movement therapy is an upper limb rehabilitation technique used in stroke patients with hemiplegia; however, studies of lower extremity rehabilitation are scarce. In this study, stroke patients with lower limb hemiplegia underwent conventional Bobath therapy for 4 weeks as baseline treatment, followed by constraint-induced movement therapy for an additional 4 weeks. The 10-m maximum walking speed and Berg balance scale scores significantly improved following treatment, and lower extremity motor function also improved. The results of functional MRI showed that constraint-induced movement therapy alleviates the reduction in cerebral functional activation in patients, which indicates activation of functional brain regions and a significant increase in cerebral blood perfusJon. These results demonstrate that constraint-induced movement therapy promotes brain functional reorganization in stroke patients with lower limb hemiplegia.

Phase Ⅰ/Ⅱ randomized controlled trial of autologous bone marrow-derived mesenchymal stem cell therapy for chronic stroke

AIM To examine the safety and efficacy of mesenchymal stem cell(MSC) therapy for intracerebral haemorrhage with neurological dysfunctions for a year.METHODS MSC were ex vivo expanded from 29 mL(17-42 mL) autologous bone marrow. Patients were randomized to have two intravenous injections of autologous MSC or placebos in four weeks apart. Neurological functions and clinical outcomes were monitored before treatment and at 12^(th), 16^(th), 24^(th), 36^(th) and 60^(th) week upon completion of^(th)e treatment. RESULTS A mean of 4.57 × 10~7(range: 1.43 × 10~7-8.40 × 10~7) MSC per infusion was administered accounting to 8.54 × 10~5(2.65 × 10~5-1.45 × 10~6) per kilogram body weight in two occasions. There was neither adverse event at time of administration nor sign of de novo tumour development among patients after monitoring for a year post MSC therapy. Neuro-restoration and clinical improvement in terms of modified Barthel index, functional independence measure and extended Glasgow Outcome Scale were evident among patients having MSC therapy compared to patients receiving placebos. CONCLUSION Intravenous administration of autologous bone marrowderived MSC is safe and has the potential of improving neurological functions in chronic stroke patients with severe disability.

Successful recanalization with multimodality endovascular interventional therapy in acute ischemic stroke

Stroke is an important cause of death and disability in adults. However, effective treatments for patients with acute ischemic stroke are limited. Intravenous recombinant tissue plasminogen activator(iv rtPA) within 4.5 h after onset has been approved as a standard treatment for patients with acute ischemic stroke. However, due to time constraints, less than one percent of acute ischemic stroke patients in Thailand are able to obtain iv rtPA. Although endovascular interventional therapy has not yet been approved as standard treatment in acute ischemic stroke, it is the one of the potentially effective treatment options. There are several reliable methods of endovascular therapy for acute ischemic stroke patients. Endovascular interventional therapy has rarely been done in Thailand. We report seven patients with successful recanalization after endovascular treatment in acute large vessel stroke from a single stroke center in Thailand. Patient screening and selection with multimodal imaging protocol and multimodality methods of endovascular interventional therapy are described.

Effect of action observation therapy on daily activities and motor recovery in stroke patients

Objective:To evaluate the effects of action observation therapy,which is based on mirror neuron theory,on upper limb function and activities of daily living in patients with stroke.Methods:Sixty-one patients with stroke were randomly divided into two groups;those in the control group received routine rehabilitation treatment and nursing,whereas those in the experimental group additionally received eight weeks of action observation therapy for 30 min,six times per week.Patients receiving action observation therapy watched videos depicting a model performing specific motor actions typically performed in daily life before enacting the same actions themselves.All patients were assessed using the FugleMeyer assessment,Barthel index and the modified Ashworth scale at baseline and at eight weeks,after treatment.Results:After the eight weeks of treatment,both groups of patients exhibited significant improvement in all the measurements(all p<0.05).Furthermore,the FugleMeyer assessment,Barthel index and modified Ashworth scale scores were significantly higher in the experimental group compared to the control group(all p<0.05).Conclusion:Action observation therapy significantly improves upper extremity motor function and performance of activities of daily living,and alleviates upper limb spasticity in patients with stroke.

Does a combined intervention program of repetitive transcranial magnetic stimulation and intensive occupational therapy affect cognitive function in patients with post-stroke upper limb hemiparesis?

Low-frequency repetitive transcranial magnetic stimulation（LF-r TMS） to the contralesional hemisphere and intensive occupational therapy（i OT） have been shown to contribute to a significant improvement in upper limb hemiparesis in patients with chronic stroke. However, the effect of the combined intervention program of LF-r TMS and i OT on cognitive function is unknown. We retrospectively investigated whether the combined treatment influence patient＇s Trail-Making Test part B（TMT-B） performance, which is a group of easy and inexpensive neuropsychological tests that evaluate several cognitive functions. Twenty-five patients received 11 sessions of LF-r TMS to the contralesional hemisphere and 2 sessions of i OT per day over 15 successive days. Patients with right- and left-sided hemiparesis demonstrated significant improvements in upper limb motor function following the combined intervention program. Only patients with right-sided hemiparesis exhibited improved TMT-B performance following the combined intervention program, and there was a significant negative correlation between Fugl-Meyer Assessment scale total score change and TMT-B performance. The results indicate the possibility that LF-r TMS to the contralesional hemisphere combined with i OT improves the upper limb motor function and cognitive function of patients with right-sided hemiparesis. However, further studies are necessary to elucidate the mechanism of improved cognitive function.

Endovascular treatment vs drug therapy alone in patients with mild ischemic stroke and large infarct cores

BACKGROUND Treatment decision making is strictly associated with the outcomes in patients with ischemic stroke who show a large core infarct.Medical care alone may result in suboptimal treatment efficacy,and endovascular treatment may be accompanied by safety issues.Whether endovascular treatment is superior to medical care is not well investigated in the clinical studies.AIM To investigate the efficacy of endovascular treatment and drug therapy alone in mild ischemic stroke patients with large infarct cores.METHODS Fifty patients with mild ischemic stroke and 50 patients with acute ischemic stroke caused by anterior large vessel occlusion were selected at the First Affiliated Hospital of Hebei North University between January 2021 and December 2021.Patients were divided into an endovascular therapy group and a drug therapy group according to different treatment methods.In the endovascular therapy group,there were 28 patients with minor stroke and 22 patients with large infarct cores.The drug therapy group had 22 patients with minor stroke and 28 patients with large infarct cores.The National Institutes of Health Stroke Scale(NIHSS) scores were collected and compared between the two groups immediately after the operation and 24 h and 7 d after the operation.The modified Rankin scale(m RS) and/or activity of daily living were assessed at hospital discharge.RESULTS There was no significant difference in NIHSS scores between the two groups before the operation(P > 0.05).NIHSS scores were lower in the endovascular therapy group than in the drug therapy group at 24 h and 7 d after the operation and at hospital discharge(all P < 0.05).The incidence of early neurologic deterioration was significantly lower in the endovascular therapy group than in the drug therapy group(P < 0.05).At hospital discharge,the m RS score was lower in the endovascular treatment group than in the drug therapy group,and the activity of daily living score was better in the endovascular treatment group than in the drug therapy group(all P < 0.05).During a follow-up of 3 mo,17 patients(34.0%) had good prognosis(m RS ≤ 2),33 patients(66.0%) had poor prognosis(m RS > 2),and 11 patients(22.0%) died.In the medical treatment group,16 patients(m RS ≤ 2) had good prognosis(32.0%),34 patients(m RS > 2) had poor prognosis(68.0%),and 14 patients(28.0%) died.There was no significant difference in prognosis and mortality between the two groups(P > 0.05).CONCLUSION Endovascular therapy can improve NIHSS score and m RS score in patients with mild ischemic stroke and large infarct cores.It is suitable for clinical application.

Neural regeneration by regionally induced stem cells within poststroke brains: Novel therapy perspectives for stroke patients

Ischemic stroke is a critical disease which causes serious neurological functional loss such as paresis. Hope for novel therapies is based on the increasing evidence of the presence of stem cell populations in the central nervous system (CNS) and the development of stem-cell-based therapies for stroke patients. Although mesenchymal stem cells (MSCs) represented initially a promising cell source, only a few transplanted MSCs were present near the injured areas of the CNS. Thus, regional stem cells that are present and/or induced in the CNS may be ideal when considering a treatment following ischemic stroke. In this context, we have recently showed that injury/ischemia-induced neural stem/progenitor cells (iNSPCs) and injury/ischemia-induced multipotent stem cells (iSCs) are present within post-stroke human brains and post-stroke mouse brains. This indicates that iNSPCs/iSCs could be developed for clinical applications treating patients with stroke. The present study introduces the traits of mouse and human iNSPCs, with a focus on the future perspective for CNS regenerative therapies using novel iNSPCs/iSCs.

Percutaneous Patent Foramen Ovale Closure versus Medical Therapy in Cryptogenic Stroke: An Update Meta-Analysis of Randomized Controlled Trials

Objectives: Concerns regarding the real efficacy of transcatheter patent foramen ovale (PFO) closure versus medical therapy in patients with cryptogenic stroke remained unresolved. We performed a meta-analysis using the randomized controlled trials on the efficacy and safety of transcatheter PFO closure in patients with cryptogenic stroke. Methods: Web of Science, EMBASE, PubMed, and the Cochrane Library were searched for relevant randomized controlled trials (RCTs). The primary outcome was recurrent stroke and transient-ischemic attack (TIA). Original data, hazard ratio (HR) with 95% confidence interval (95% CI) were abstracted to calculate a pooled effect size. Results: Our meta-analysis showed benefit with device closure when compared with medical therapy with an HR of 0.54 (95% CI: 0.39 - 0.74, P = 0.108) in the intention-to-treat cohort, 0.44 (95% CI: 0.24 - 0.82, P = 0.103) in the per-protocol populations, and 0.43 (95% CI: 0.31 - 0.60, P = 0.019) in the as-treated populations. There was a significantly higher incidence of new-onset atrial fibrillation in PFO closure patients (OR = 4.53, 95% CI: 2.58 - 7.97, P = 0.094). PFO Patients with an atrial septal aneurysm benefit from device closure (OR = 0.39, 95% CI: 0.22 - 0.69, P = 0.053). Patients with a substantial PFO shunt benefit the greatest with device closure with a pooled OR of 0.27 (95% CI: 0.14 - 0.56, P = 0.525). Conclusions: The meta-analysis concluded that PFO closure was associated with significantly lower risk of recurrent stroke in PFO patients with cryptogenic stroke than with medical therapy alone. The benefit of PFO closure was greater in patients with a substantial shunt and atrial septal aneurysm. PFO closure was associated with higher rates of new-onset atrial fibrillation.

Withania somnifera: a pre-clinical study on neuroregenerative therapy for stroke

Stroke management exerts insurmountable societal and economic burden on the patient as well as their caregivers. In the year 2010 alone, the direct and indirect costs of stroke care amounted to 36.5 billion dollars （Go et al., 2014）. Despite concentrated efforts to develop a safe, effective drug for stroke, we have not discovered one since the introduction of recombinant tissue plasminogen activator （rtPA）--the standalone FDA-approved therapy for stroke. While rtPA is highly effective, it needs to be given within 3-4.5 hours of the onset of stroke symptoms （Zivin, 2009）. This is often complicated by the delay in the commencement of treatment due to preliminary inclusion parameters that are required to be ascertained before rtPA administration.