Recovery In Ischemic Stroke Patients Research Articles

High-frequency magnetic paired associated stimulation promotes motor function recovery in ischemic stroke patients: a study protocol for single-center, sham stimulation randomized controlled trials (H2MPAS)

BackgroundNumerous studies have validated the clinical effectiveness of electromagnetic pairing-associated stimulation. Building upon this foundation, we have developed a novel approach involving high-frequency magnetic paired-associated stimulation, aiming to enhance clinical applicability and potentially improve efficacy. However, the clinical effectiveness of this approach remains unclear. Our objective is to demonstrate the therapeutic efficacy of this novel approach by employing high-frequency pairing to intervene in patients experiencing motor dysfunction following a stroke.MethodsThis is a single-center, single-blind, sham stimulation controlled clinical trial involving patients with upper limb motor dysfunction post-stroke. The intervention utilizes paired magnetic stimulation, combining peripheral and central magnetic stimulation, in patients with Brunnstrom stage III–V stroke lasting from 3 months to 1 year. Evaluation of patients’ upper limb motor function occurred before the intervention and after 3 weeks of intervention. Follow-up visits will be conducted after 5 weeks and 3 months of intervention. The primary outcome measure is the Action Research Arm Test, with secondary measures including the Fugl-Meyer Assessment-upper, Modified Barthel Index, modified Tardieu scale, functional near-infrared spectroscopy, and neuroelectrophysiology.DiscussionThe high-frequency magnetic paired associative stimulation used in this study combined high-frequency magnetic stimulation with paired stimulation, potentially facilitating both cortical excitation through high-frequency stimulation and specific circuit enhancement through paired stimulation. As dual-coil magnetic stimulation equipment becomes increasingly popular, magnetic-magnetic paired associated stimulation may offer patients improved clinical outcomes at reduced costs.Trial registrationChinese Clinical Trial Registry,ChiCTR2400083363. Registered on 23 April 2024.

A lesion‐aware automated processing framework for clinical stroke magnetic resonance imaging

AbstractMagnetic resonance imaging (MRI) and MRI based computational modelling studies provide insights into severity and recovery of ischemic stroke patients. The presence of brain lesions, however, can heavily distort and impair state‐of‐the‐art processing frameworks due to abnormal intensity values and tissue distortions. In this study, we introduce and validate the novel “Lesion Aware automated Processing Pipeline (LeAPP).” LeAPP automatically processes clinical stroke MRI data while significantly reducing the impact of pathological artefacts on processing outputs such as structural and functional connectomes (SC, FC). This helps to advance the identification of biomarkers for recovery and mechanism‐based intervention planning using MRI as well as computational approaches. We extended existing frameworks, such as the Human Connectome Project (HCP) minimal processing pipeline, introducing correction steps, and implementing and modifying functional and diffusion processing to cope with MRI acquisition protocols more typical for the clinical context. A total of 51 participants (36 patients, 15 age‐matched controls) were processed across four time points for patients (3–5, 30–40, 85–95, 340–380 days after stroke onset) and one time point for controls. We validated performance using artificial lesioned brains (N = 81), derived from healthy brains and informed by real stroke lesions. The quality of reconstructing the ground truth was quantified on whole brain level and for lesion affected and unaffected regions‐of‐interest (ROIs) for brain parcellations and for SCs. Volume based agreement was evaluated using metrics such as dice coefficient, volume difference or ROI center‐of‐gravity distance while SC based agreement was defined as the difference in network metrics (e.g., node strength, clustering coefficient, or centrality). The observed deviations in reconstructed ground truth brain parcellations and structural connectomes from lesioned brains were significantly reduced for LeAPP, compared to the performance of existing pipelines such as HCP minimal processing pipeline. For instance, in the case of lesion affected ROIS we achieved a mean dice coefficient (where a value of one represents total agreement as defined by an exact overlap of both ROIs) of 0.81 with LeAPP, compared to 0.75 for HCP (p < .0001*). Additionally, the average measured ROI distance (where a value of zero represents no difference) for lesion ROIs was 0.87 for LeAPP in contrast to 1.7 for HCP (p < .0001*), indicating an overall superior performance of LeAPP. The pipeline generates standardized output files ready for brain network modelling for instance with The Virtual Brain software. This novel open‐source automated processing framework contributes to reproducible research and provides a robust framework for automated processing of clinical stroke MRI data, supporting the identification of brain network‐based biomarkers of stroke recovery.

Association of IL-6 rs1800795, but not TNF-α rs1800629, and IL-1β rs16944 polymorphisms’ genotypes with recovery of ischemic stroke patients following thrombolysis

ABSTRACT Objectives Inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 can cause brain injury, slow recovery, and adverse effects (ADEs) in ischemic stroke (IS) patients treated with recombinant tissue plasminogen activator (rtPA). We explored the relationship between selected polymorphisms within TNF-α, IL-1β and IL-6 genes, and post-IS outcome and ADEs in patients treated with rtPA. Methods One hundred and sixty-six patients with IS treated with rtPA were included in this study. The modified Rankin Scale (mRS) was used to assess functional recovery 3 months after IS likewise thrombolytic therapy efficacy. Patients were classified into groups with favorable (0–1) or poor recovery based on their mRS score at the ninetieth day post-IS. During hospitalization, ADEs following rtPA were monitored. TNF-α-308 G/A (rs1800629), IL-1β-511 G/A (rs16944), and IL-6-174 G/C (rs1800795) polymorphisms were genotyped using Real-Time PCR. SPSS software version 22.0 was used for statistical analyses. Results Patients with the TNF-α-308 G/A GG genotype had a higher mean NIHSS value at admission (12.75 ± 5.176) than those carrying A-allele (10.56 ± 3.979;p = 0.016). Individuals with the CC genotype of the IL-6-174 G/C polymorphism had significantly lower NIHSS scores (8.79 ± 5.053) than those with G-allele (12.06 ± 6.562) 24 hours after rtPA (p = 0.050). Patients with the GG genotype of the IL-6-174 G/C polymorphism had a significantly poorer outcome (p = 0.024; OR = 2.339; 95%CI 1.121–4.880), while patients who were G-allele carriers of the Il-6–174 G/C polymorphism and had the AA genotype of the IL-1β-511 G/A polymorphism were statistically significantly more likely to experience hemorrhagic transformation (p = 0.046; OR = 2.7273; 95%CI 1.0414–7.1426). Conclusion GG genotype of the IL-6-174 G/C polymorphism is associated with poor recovery after IS treated with rtPA therapy.

Quality metrics in the management of acute stroke in Greece during the first 5 years of Registry of Stroke Care Quality (RES-Q) implementation.

Establishment of a prospective stroke registry may promote the documentation and improvement of acute stroke care. We present the status of stroke management in Greece using the Registry of Stroke Care Quality (RES-Q) dataset. Consecutive patients with acute stroke were prospectively registered in RES-Q registry by contributing sites in Greece during the years 2017-2021. Demographic and baseline characteristics, acute management, and clinical outcomes at discharge were recorded. Stroke quality metrics, with a specific interest in the association between acute reperfusion therapies and functional recovery in ischemic stroke patients are presented. A total of 3590 acute stroke patients were treated in 20 Greek sites (61% men, median age 64 years; median baseline NIHSS 4; 74% ischemic stroke). Acute reperfusion therapies were administered in almost 20% of acute ischemic stroke patients, with a door to needle and door to groin puncture times of 40 and 64 min, respectively. After adjustment for contributing sites, the rates of acute reperfusion therapies were higher during the time epoch 2020-2021 compared to 2017-2019 (adjusted OR 1.31; 95% CI 1.04-1.64; p < 0.022; Cochran-Mantel-Haenszel test). After propensity-score-matching, acute reperfusion therapies administration was independently associated with higher odds of reduced disability (one point reduction across all mRS scores) at hospital discharge (common OR 1.93; 95% CI 1.45-2.58; p < 0.001). Implementation and maintenance of a nationwide stroke registry in Greece may guide the stroke management planning, so that prompt patient transportation, acute reperfusion therapies, and stroke unit hospitalization become more widely accessible, improving the functional outcomes of stroke patients.

Circulating MicroRNAs and Extracellular Vesicle-Derived MicroRNAs as Predictors of Functional Recovery in Ischemic Stroke Patients: A Systematic Review and Meta-Analysis.

Stroke accounts for the second leading cause of death and a major cause of disability, with limited therapeutic strategy in both the acute and chronic phases. Blood-based biomarkers are intensively researched and widely recognized as useful tools to predict the prognoses of patients confronted with therapeutically limited diseases. We performed a systematic review of the circulating biomarkers in IS patients with prognostic value, with a focus on microRNAs and exosomes as predictive biomarkers of motor and cognitive recovery. We identified 63 studies, totalizing 72 circulating biomarkers with prognostic value in stroke recovery, as follows: 68 miRNAs and exosomal-miRNAs being identified as predictive for motor recovery after stroke, and seven biomarkers being predictive for cognitive recovery. Twelve meta-analyses were performed using effect sizes (random-effects and fixed-effects model). The most significant correlation findings obtained after pooling were with miR-21, miR-29b, miR-125b-5p, miR-126, and miR-335. We identified several miRNAs that were correlated with clinical outcomes of stroke severity and recovery after ischemic stroke, providing predictive information on motor and cognitive recovery. Based on the current state of research, we identified serum miR-9 and neutrophil miR-29b as the most promising biomarkers for in-depth follow-up studies, followed by serum miR-124 and plasma miR-125b.

The Combination of Whole-Brain Features and Local-Lesion Features in DSC-PWI May Improve Ischemic Stroke Outcome Prediction.

Accurate and reliable outcome predictions can help evaluate the functional recovery of ischemic stroke patients and assist in making treatment plans. Given that recovery factors may be hidden in the whole-brain features, this study aims to validate the role of dynamic radiomics features (DRFs) in the whole brain, DRFs in local ischemic lesions, and their combination in predicting functional outcomes of ischemic stroke patients. First, the DRFs in the whole brain and the DRFs in local lesions of dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) images are calculated. Second, the least absolute shrinkage and selection operator (Lasso) is used to generate four groups of DRFs, including the outstanding DRFs in the whole brain (Lasso (WB)), the outstanding DRFs in local lesions (Lasso (LL)), the combination of them (combined DRFs), and the outstanding DRFs in the combined DRFs (Lasso (combined)). Then, the performance of the four groups of DRFs is evaluated to predict the functional recovery in three months. As a result, Lasso (combined) in the four groups achieves the best AUC score of 0.971, which improves the score by 8.9% compared with Lasso (WB), and by 3.5% compared with Lasso (WB) and combined DRFs. In conclusion, the outstanding combined DRFs generated from the outstanding DRFs in the whole brain and local lesions can predict functional outcomes in ischemic stroke patients better than the single DRFs in the whole brain or local lesions.

Therapeutic Benefits of Adropin in Aged Mice After Transient Ischemic Stroke via Reduction of Blood-Brain Barrier Damage.

Adropin is a peptide encoded by the energy homeostasis-associated gene (Enho) that is highly expressed in the brain. Aging and stroke are associated with reduced adropin levels in the brain and plasma. We showed that treatment with synthetic adropin provides long-lasting neuroprotection in permanent ischemic stroke. However, it is unknown whether the protective effects of adropin are observed in aged animals following cerebral ischemia/reperfusion. We hypothesized that adropin provides neuroprotection in aged mice subjected to transient middle cerebral artery occlusion. Aged (18-24 months old) male mice were subjected to 30 minutes of middle cerebral artery occlusion followed by 48 hours or 14 days of reperfusion. Sensorimotor (weight grip test and open field) and cognitive tests (Y-maze and novel object recognition) were performed at defined time points. Infarct volume was quantified by 2,3,5-triphenyltetrazolium chloride staining at 48 hours or Cresyl violet staining at 14 days post-middle cerebral artery occlusion. Blood-brain barrier damage, tight junction proteins, and MMP-9 (matrix metalloproteinase-9) were assessed 48 hours after middle cerebral artery occlusion by ELISA and Western blots. Genetic deletion of Enho significantly increased infarct volume and worsened neurological function, whereas overexpression of adropin dramatically reduced stroke volume compared to wild-type controls. Postischemic treatment with synthetic adropin peptide given at the onset of reperfusion markedly reduced infarct volume, brain edema, and significantly improved locomotor function and muscular strength at 48 hours. Delayed adropin treatment (4 hours after the stroke onset) reduced body weight loss, infarct volume, and muscular strength dysfunction, and improved long-term cognitive function. Postischemic adropin treatment significantly reduced blood-brain barrier damage. This effect was associated with reduced MMP-9 and preservation of tight junction proteins by adropin treatment. These data unveil a promising neuroprotective role of adropin in the aged brain after transient ischemic stroke via reducing neurovascular damage. These findings suggest that poststroke adropin therapy is a potential strategy to minimize brain injury and improve functional recovery in ischemic stroke patients.

Frontoparietal network activation is associated with motor recovery in ischemic stroke patients

Strokes cause lesions that damage brain tissue, disrupt normal brain activity patterns and can lead to impairments in motor function. Although modulation of cortical activity is central to stimulation-based rehabilitative therapies, aberrant and adaptive patterns of brain activity after stroke have not yet been fully characterized. Here, we apply a brain dynamics analysis approach to study longitudinal brain activity patterns in individuals with ischemic pontine stroke. We first found 4 commonly occurring brain states largely characterized by high amplitude activations in the visual, frontoparietal, default mode, and motor networks. Stroke subjects spent less time in the frontoparietal state compared to controls. For individuals with dominant-hand CST damage, more time spent in the frontoparietal state from 1 week to 3-6 months post-stroke was associated with better motor recovery over the same time period, an association which was independent of baseline impairment. Furthermore, the amount of time spent in brain states was linked empirically to functional connectivity. This work suggests that when the dominant-hand CST is compromised in stroke, resting state configurations may include increased activation of the frontoparietal network, which may facilitate compensatory neural pathways that support recovery of motor function when traditional motor circuits of the dominant-hemisphere are compromised.

Research advances in prevention and treatment of cerebral ischemia-reperfusion injury by targeting mitochondrial quality control

Cerebral ischemia-reperfusion injury(CIRI) is an important factor hindering the recovery of ischemic stroke patients after blood flow recanalization. Mitochondria, serving as the &quot;energy chamber&quot; of cells, have multiple important physiological functions, such as supplying energy, metabolizing reactive oxygen species, storing calcium, and mediating programmed cell death. During CIRI, oxidative stress, calcium overload, inflammatory response, and other factors can easily lead to neuronal mitochondrial dyshomeostasis, which is the key pathological link leading to secondary injury. As reported, the mitochondrial quality control(MQC) system, mainly including mitochondrial biosynthesis, kinetics, autophagy, and derived vesicles, is an important endogenous mechanism to maintain mitochondrial homeostasis and plays an important protective role in the damage of mitochondrial structure and function caused by CIRI. This paper reviewed the mechanism of MQC and the research progress on MQC-targeting therapy of CIRI in recent 10 years to provide theoretical references for exploring new strategies for the prevention and treatment of ischemic stroke with traditional Chinese medicine.

Lactobacillus plantarum-derived extracellular vesicles protect against ischemic brain injury via the microRNA-101a-3p/c-Fos/TGF-β axis

Currently, the reported source of extracellular vesicles (EVs) for the treatment of ischemic stroke（IS）is limited to mammals. Moreover, these EVs are restricted to clinical translation by the high cost of cell culture. In this respect, Lactobacillus plantarum culture is advantaged by low cost and high yield. However, it is poorly understood whether Lactobacillus plantarum-derived EVs (LEVs) are applicable for the treatment of IS. Here, our results demonstrated that LEVs reduced apoptosis in ischemic neuron both in vivo and in vitro. As revealed by high-throughput sequencing, miR-101a-3p expression was significantly elevated by LEV treatment in OGD/R-induced neurons, as confirmed in the tMCAO mice treated with LEVs. Mechanistically, c-Fos was directly targeted by miR-101a-3p. In addition, c-Fos determined ischemia-induced neuron apoptosis in vivo and in vitro through the TGF-β1 pathway, miR-101a-3p inhibition aggravated ischemia-induced neuron apoptosis in vitro and in vivo, and miR-101a-3p overexpression produced the opposite results. Hsa-miR-101–3p was downregulated in the plasma of patients with IS but upregulated in the patients with neurological recovery after rt-PA intravenous thrombolysis. In conclusion, Our results demonstrated for the first time that LEVs might inhibit neuron apoptosis via the miR-101a-3p/c-Fos/TGF-β axis, and has-miR-101–3p is a potential marker of neurological recovery in IS patients.

Prediction of motor recovery after ischemic stroke: Clinical and diffusion tensor imaging study

BackgroundThe severity of stroke-induced disruption to the corticospinal tract (CST) would be predictable to affect motor outcome. Diffusion tensor imaging (DTI) is a noninvasive technique that can be applied to assess the structural integrity of the CST. Aim of the workTo assess the value of DTI in patients early presenting with acute ischemic stroke as a prognostic modality to predict the clinical outcome Patients and methodsThirty-four patients with acute ischemic stroke underwent clinical assessment using the National Institutes of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), Medical Research Council (MRC) score, Morticity Index (MI), and DTI to detect the degree of reduction of fractional anisotropy (FA), and pattern of CST at baseline and after 6 months follow up. Seventeen age, sex matched controls underwent DTI assessment. ResultsThe stroke patients showed a significant reduction in the baseline FA values of the CSTs on the affected sides compared to the contralateral sides and controls. Moreover, they showed lower mean baseline FA lesion side and FA ratio(rFA) compared to follow up. The patients with high baseline FA, rFA showed good recovery response with cut off values of 0.483, 0.948 respectively. There was a significant negative correlation between baseline FA on the lesion side, rFA and follow up NIHSS, and MRS scores and they had a significant positive correlation with follow up MI scores. Conclusion: Patients with higher baseline FA, rFA values were correlated with better motor recovery, and could predict the motor recovery in ischemic stroke patients.

Potential Neurogenesis and Neuroprotective Effects of Epigallocatechin-3-gallate (EGCG) in Green Tea (Camellia sinensis) Through Microglia M2 Induction Process and NLRP3 Inhibition as an Innovation for Ischemic Stroke Adjuvant Therapy: A Review

Stroke is a condition that results from the obstruction or rupture of blood arteries in the brain, cutting off blood flow to the brain and causing the death of brain cells. Stroke is divided into two types based on the cause: ischemic stroke and hemorrhagic stroke. Ischemic stroke is the most common kind of stroke, accounting for around 87% of all strokes. The high occurrence of ischemic stroke has a wide-ranging influence on society. Because ischemic stroke still has a high prevalence and limited treatment options, a therapeutic breakthrough that can assist reduce mortality and morbidity from stroke, particularly ischemic stroke, is needed. Consuming green tea (Camellia sinensis), which has neurogenetic and neuroprotective benefits, is one of the advances that can be used. This literature was compiled through online searches using Pubmed, Sciencedirect, NIH NCBI, and Google Scholar instruments. It is known that green tea with the active ingredient Epigallocatechin-3-gallate (EGCG) has the potential to induce neurogenesis in ischemic conditions by inducing microglia to polarize to M2 and can inhibit pro-inflammatory mediators through inhibition of NOD-like Receptor Protein-3 (NLRP3) so that the pyroptosis process will also be inhibited, in this way EGCG also has the potential to become an ingredient that provides a neuroprotective effect. These two major processes will aid in the recovery of ischemic stroke patients.

The disrupted topological properties of structural networks showed recovery in ischemic stroke patients: a longitudinal design study

IntroductionStroke is one of the leading causes of substantial disability worldwide. Previous studies have shown brain functional and structural alterations in adults with stroke. However, few studies have examined the longitudinal reorganization in whole-brain structural networks in stroke.MethodsHere, we applied graph theoretical analysis to investigate the longitudinal topological organization of white matter networks in 20 ischemic stroke patients with a one-month interval between two timepoints. Two sets of clinical scores, Fugl-Meyer motor assessment (FMA) and neurological deficit scores (NDS), were assessed for all patients on the day the image data were collected.ResultsThe stroke patients exhibited significant increases in FMA scores and significant reductions in DNS between the two timepoints. All groups exhibited small-world organization (σ > 1) in the brain structural network, including a high clustering coefficient (γ > 1) and a low normalized characteristic path length (λ ≈ 1). However, compared to healthy controls, stroke patients showed significant decrease in nodal characteristics at the first timepoint, primarily in the right supplementary motor area, right middle temporal gyrus, right inferior parietal lobe, right postcentral gyrus and left posterior cingulate gyrus. Longitudinal results demonstrated that altered nodal characteristics were partially restored one month later. Additionally, significant correlations between the nodal characteristics of the right supplementary motor area and the clinical scale scores (FMA and NDS) were observed in stroke patients. Similar behavioral-neuroimaging correlations were found in the right inferior parietal lobe.ConclusionAltered topological properties may be an effect of stroke, which can be modulated during recovery. The longitudinal results and the neuroimaging-behavioral relationship may provide information for understanding brain recovery from stroke. Future studies should detect whether observed changes in structural topological properties can predict the recovery of daily cognitive function in stroke.

Cerebrolysin Combined with Rehabilitation Enhances Motor Recovery and Prevents Neural Network Degeneration in Ischemic Stroke Patients with Severe Motor Deficits.

The objective of this study was to evaluate whether Cerebrolysin combined with rehabilitation therapy supports additional motor recovery in stroke patients with severe motor impairment. This study analyzed the combined data from the two phase IV prospective, multicenter, randomized, double-blind, placebo-controlled trials. Stroke patients were included within seven days after stroke onset and were randomized to receive a 21-day treatment course of either Cerebrolysin or placebo with standardized rehabilitation therapy. Assessments were performed at baseline, immediately after the treatment course, and 90 days after stroke onset. The plasticity of the motor system was assessed by diffusion tensor imaging and resting state fMRI. In total, 110 stroke patients were included for the full analysis set (Cerebrolysin n = 59, placebo n = 51). Both groups showed significant motor recovery over time. Repeated-measures analysis of varianceshowed a significant interaction between time and type of intervention as measured by the Fugl–Meyer Assessment (p < 0.05). The Cerebrolysin group demonstrated less degenerative changes in the major motor-related white matter tracts over time than the placebo group. In conclusion, Cerebrolysin treatment as an add-on to a rehabilitation program is a promising pharmacologic approach that is worth considering in order to enhance motor recovery in ischemic stroke patients with severe motor impairment.

Does the Initiation of Fluoxetine Postacute Stroke Result in Improved Functional Recovery?: A Critically Appraised Topic.

Stroke is a leading cause of disability worldwide. Selective serotonin reuptake inhibitors are often prescribed following stroke due to high rates of depression. Interest in selective serotonin reuptake inhibitor use for poststroke motor and functional recovery was generated after the publication of the Fluoxetine for motor recovery after acute ischemic stroke (FLAME) trial in 2011, which showed improved motor recovery in ischemic stroke patients with moderate to severe motor deficits. The objective of this study was to critically assess current evidence regarding the use of fluoxetine compared with placebo for poststroke functional recovery. The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario and question, literature search, critical appraisal, results, evidence summary, commentary, and clinical bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, clinical epidemiologists, and content experts in the field of cerebrovascular neurology and physical medicine and rehabilitation. A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared the functional outcomes of subjects poststroke receiving fluoxetine versus placebo. There was no significant difference in functional outcome measured by the Modified Rankin Scale between the 2 groups. Prespecified secondary analysis showed significantly decreased rates of depression in the fluoxetine group, but significantly increased rates of bone fracture. Among patients with stroke, early initiation of fluoxetine did not result in improved functional recovery. Lower rates of depression were observed in the fluoxetine-treated group; however these patients experienced higher rates of bone fracture.

Regulatory T cells participate in the recovery of ischemic stroke patients

BackgroundRecent preclinical studies have shown that regulatory T cells (Treg) play a key role in the immune response after ischemic stroke (IS). However, the role of Treg in human acute IS has been poorly investigated. Our aim was to study the relationship between circulating Treg and outcome in human IS patients.MethodsA total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale ≤2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg was measured at admission, 48, 72 h and at day 7 after stroke onset.ResultsCirculating Treg levels were higher in IS patients compared to control subjects. Treg at 48 h were independently associated with good functional outcome (OR, 3.5; CI: 1.9–7.8) after adjusting by confounding factors. Patients with lower Treg at 48 h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg at 48 h (r = − 0.414) and 72 h (r = − 0.418) and infarct volume.ConclusionsThese findings suggest that Treg may participate in the recovery of IS patients. Therefore, Treg may be considered a potential therapeutic target in acute ischemic stroke.

A Systems Analysis of the Relationships Between Anemia and Ischemic Stroke Rehabilitation Based on RNA-Seq Data

Ischemic stroke (IS) is one of the main causes of morbidity and disability worldwide due to its complex mechanism. Anemia was characterized as a risk factor of IS because the direct connection between central nervous system, blood supply, and tissue oxygen delivery. As the key oxygen-carrying molecule in the blood, hemoglobin (Hb) may be decisive in the destiny of penumbral area or influence the brain recovery and neurologic function, which could finally affect the outcome of IS. However, more detailed information on the expression levels of Hb related genes were still lacking possibly because the concentration of Hb was determined by the genes’ expression several hours ago, which may make the research more difficult to perform. This time gap between gene expressions and protein concentration could make these genes predictive bio-markers for IS outcome. In this study, we choose 28 IS patients, of which 12 were suffering from anemia. Statistical analysis results showed that the outcomes of the patients were different when dividing them into two groups characterized by Hb concentration. 2 sex and age matched patients were first chosen to perform RNA-seq analysis on, on two occasions at two different time points, after which the Hb counts were tested at least 24 h after sequencing. Results showed that the outcome of anemia patients was poor compared with non-anemia patients. Two other patients were then chosen for analysis which excluded the coincidence of other factors. The results showed that the low value of Hb under 13 g/dL in men were closely related to the poor outcome of IS patients. Differently expressed Hb related genes were tested and six genes were shown to be positively correlated with the recovery degree of IS patients: ELANE, FGF23, HBB, PIEZO1, RASA4, and PRTN3. Gene CPM was shown to be negatively correlated with clinical outcomes. All of the seven genes were validated to be related to strokes using real-time PCR or literature searches. Taken together, these genes could be considered as new predictors for the recovery of IS patients.

Leukoaraiosis Predicts Short-term Cognitive But not Motor Recovery in Ischemic Stroke Patients During Rehabilitation

Background: Leukoaraiosis has been shown to impact functional outcomes after acute ischemic stroke. However, its association with domain specific recovery after ischemic stroke is uncertain. We sought to determine whether pre-existing leukoaraiosis is associated with short-term motor and cognitive recovery after stroke. Methods: We retrospectively studied ischemic stroke patients admitted to acute inpatient rehabilitation (AIR) between January 2013 and September 2015. Patient baseline characteristics, infarct volume, prestroke modified Rankin Scale, stroke cause, rehabilitation length of stay, and Functional Independence Measure (FIM) scores were recorded. Leukoaraiosis severity was graded on brain magnetic resonance imaging using the Fazekas scale. Multiple linear regression was used to determine factors independently associated with the total, cognitive, and motor FIM scores at AIR discharge, respectively. Results: Of 1600 ischemic stroke patients screened, 109 patients were included in the final analysis. After adjustment, the initial National Institute of Health Stroke Scale (β −0.541, confidence interval [CI] −0.993 to −0.888; P = 0.020) and pre-existing leukoaraiosis severity (β −1.448, CI −2.861 to −0.034; P = 0.045) independently predicted the total FIM score. Domain specific analysis showed that infarct volume (β −0.012, CI −0.019 to −0.005; P = 0.002) and leukoaraiosis severity (β −0.822, CI −1.223 to −0.410; P = 0.0001) independently predicted FIM cognitive scores at discharge from AIR. Leukoaraiosis did not predict FIM motor score (P = 0.17). Conclusions: Leukoaraiosis severity is an independent predictor of total and cognitive, but not motor FIM scores after AIR for acute ischemic stroke. This highlights that leukoaraiosis affects poststroke recovery in a domain specific fashion, information that may aid counseling of patients and families as well as tailor rehabilitative efforts.

The efficacy comparison of citalopram, fluoxetine, and placebo on motor recovery after ischemic stroke: a double-blind placebo-controlled randomized controlled trial

Objective: The present study aimed to assess the effectiveness of oral citalopram, compared with fluoxetine and a placebo, in patients with post-stroke motor disabilities. Design: A randomized double-blind placebo-controlled clinical trial was conducted between January 2015 and January 2016. Setting: The neurology department of a university-affiliated urban hospital in Tehran, Iran. Subjects: Ninety adult patients with acute ischemic stroke, hemiplegia, or hemiparesis and a Fugl-Meyer Motor Scale score of below 55 were included. Interventions: Participants were randomly allocated to one of three groups: Group A received 20 mg PO of fluoxetine daily, Group B received 20 mg PO of citalopram daily, and Group C received a placebo PO The duration of the therapy was 90 days. In addition to the medications, all of the participants received physiotherapy. Main measures: Functional status at 90 days, which was measured by the Fugl-Meyer Motor Scale score. Results: The initial mean (SD) Fugl-Meyer Motor Scale scores for the placebo, fluoxetine, and citalopram groups were 18.2 (11.42), 20.08 (14.53), and 17.07 (14.92), respectively. After 90 days, the scores were 27.96 (18.71) for the placebo group, 52.42 (26.24) for the fluoxetine group, and 50.89 (27.17) for the citalopram group. Compared with the placebo group, the mean Fugl-Meyer Motor Scale scores showed significant increases in the fluoxetine and citalopram groups (P = 0.001). Conclusion: There was no significant difference between citalopram and fluoxetine in facilitating post-stroke motor recovery in ischemic stroke patients. However, compared with a placebo, both drugs improved post-stroke motor function.

Prognostic models for complete recovery in ischemic stroke: a systematic review and meta-analysis

BackgroundPrognostic models have been increasingly developed to predict complete recovery in ischemic stroke. However, questions arise about the performance characteristics of these models. The aim of this study was to systematically review and synthesize performance of existing prognostic models for complete recovery in ischemic stroke.MethodsWe searched journal publications indexed in PUBMED, SCOPUS, CENTRAL, ISI Web of Science and OVID MEDLINE from inception until 4 December, 2017, for studies designed to develop and/or validate prognostic models for predicting complete recovery in ischemic stroke patients. Two reviewers independently examined titles and abstracts, and assessed whether each study met the pre-defined inclusion criteria and also independently extracted information about model development and performance. We evaluated validation of the models by medians of the area under the receiver operating characteristic curve (AUC) or c-statistic and calibration performance. We used a random-effects meta-analysis to pool AUC values.ResultsWe included 10 studies with 23 models developed from elderly patients with a moderately severe ischemic stroke, mainly in three high income countries. Sample sizes for each study ranged from 75 to 4441. Logistic regression was the only analytical strategy used to develop the models. The number of various predictors varied from one to 11. Internal validation was performed in 12 models with a median AUC of 0.80 (95% CI 0.73 to 0.84). One model reported good calibration. Nine models reported external validation with a median AUC of 0.80 (95% CI 0.76 to 0.82). Four models showed good discrimination and calibration on external validation. The pooled AUC of the two validation models of the same developed model was 0.78 (95% CI 0.71 to 0.85).ConclusionsThe performance of the 23 models found in the systematic review varied from fair to good in terms of internal and external validation. Further models should be developed with internal and external validation in low and middle income countries.