Assessment of corticospinal tract remodeling based on diffusion tensor imaging in the treatment of motor dysfunction after ischemic stroke by acupuncture: A meta-analysis.

BACKGROUND: To investigate the efficacy of acupuncture in improving motor dysfunction after ischemic stroke (IS) and to investigate the effect of acupuncture on corticospinal tract (CST) remodeling using diffusion tensor imaging. METHODS: Published literature on the effect of acupuncture on CST remodeling after IS using diffusion tensor imaging in the form of randomized controlled trials (RCTs) were systematically retrieved and screened from Cochrane Library, Web of Science, PubMed, Embase, CNKI, CBM, VIP, and Wanfang databases from inception to December 2022. The methodological quality of the included studies was critically and independently evaluated by 2 reviewers using the Cochrane Risk of Bias Assessment Tool for RCTs. The correlated data were extracted using the pre-designed form, and all analyses were performed using Reviewer Manager version 5.4. RESULTS: Eleven eligible RCTs involving 459 patients were eventually included. The combined evidence results showed that the acupuncture group significantly improved patients' National Institute of Health stroke scale, Fugl-Meyer Assessment Scale, and Barthel index compared with conventional medical treatment. The acupuncture group significantly promoted remodeling of the CST, as reflected by an increase in fractional anisotropy (FA) throughout the CST [MD = 0.04, 95% CI (0.02, 0.07), P = .001], and in addition, subgroup analysis showed that the acupuncture group significantly improved FA in the infarct area compared with conventional medical treatment at around 4 weeks [MD = 0.04, 95% CI (0.02, 0.06), P = .0002] and FA of the affected cerebral peduncle [MD = 0.03, 95% CI (0.00, 0.07), P = .02]. Also, compared with conventional medical treatment, the acupuncture group significantly increased average diffusion coefficient of the affected cerebral peduncle [MD = -0.21, 95% CI (-0.28, -0.13), P < .00001]. CONCLUSION: The results of the meta-analysis suggest that acupuncture therapy can improve the clinical manifestations of motor dysfunction in patients after IS and advance a possibly beneficial effect on CST remodeling. However, due to the number and quality of eligible studies, these findings need to be further validated in more standardized, rigorous, high-quality clinical trials.

Longitudinal Monitoring of Microstructural Alterations in Cerebral Ischemia with in Vivo Diffusion-weighted MR Spectroscopy.

Background The time course of cellular damage after acute ischemic stroke (IS) is currently not well known, and specific noninvasive markers of microstructural alterations linked to inflammation are lacking, which hinders the monitoring of anti-inflammatory treatment. Purpose To evaluate the temporal pattern of neuronal and glial microstructural changes after stroke using in vivo single-voxel diffusion-weighted MR spectroscopy. Materials and Methods In this prospective longitudinal study, participants with IS and healthy volunteers (HVs) underwent MRI at 3.0 T. In participants with IS, apparent diffusion coefficients (ADCs) and concentrations of total N-acetyl-aspartate (tNAA), total creatine (tCr), and total choline (tCho) were measured in volumes of interest (VOIs), including the lesion VOI (VOIles) and the contralateral VOI (VOIcl) at 2 weeks, 1 month, and 3 months after IS. HVs were examined once, with VOIs located in the same brain regions as participants with IS. Within- and between-group differences and longitudinal changes were examined using linear mixed-effects models. Results Twenty participants with IS (mean age, 61 years ± 13 [SD]; 12 women) and 20 HVs (mean age, 59 years ± 13; 12 women) were evaluated. No differences in ADCs or concentrations were observed in VOIcl between HVs and participants with IS. In participants with IS, the ADC of tCr was higher in VOIles than in VOIcl at 1 month (+14.4%, P = .004) and 3 months after IS (+19.0%, P < .001), while the ADC of tCho was higher only at 1 month (+16.7%, P = .001). No difference in the ADC of tNAA was observed between the two VOIs at any time point. tNAA and tCr concentrations were lower in VOIles than in VOIcl and were stable over time (approximately -50% and -30%, respectively; P < .001). Conclusion High diffusivity of choline-containing compounds and total creatine (tCr) in the ischemic lesion 1 month after ischemic stroke (IS) indicates glial morphologic changes, suggesting that active inflammation is still ongoing at this time point. High tCr diffusivity up to 3 months after IS likely reflects the presence of astrogliosis at the chronic stage of cerebral ischemia. Clinical trial registration no. NCT02833961 © RSNA, 2022 Online supplemental material is available for this article.

Outcome after acute ischemic stroke is linked to sex-specific lesion patterns.

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.

Real-World Experience with Artificial Intelligence-Based Triage in Transferred Large Vessel Occlusion Stroke Patients.

BACKGROUND AND PURPOSE: Randomized controlled trials have demonstrated the importance of time to endovascular therapy (EVT) in clinical outcomes in large vessel occlusion (LVO) acute ischemic stroke. Delays to treatment are particularly prevalent when patients require a transfer from hospitals without EVT capability onsite. A computer-aided triage system, Viz LVO, has the potential to streamline workflows. This platform includes an image viewer, a communication system, and an artificial intelligence (AI) algorithm that automatically identifies suspected LVO strokes on CTA imaging and rapidly triggers alerts. We hypothesize that the Viz application will decrease time-to-treatment, leading to improved clinical outcomes. METHODS: A retrospective analysis of a prospectively maintained database was assessed for patients who presented to a stroke center currently utilizing Viz LVO and underwent EVT following transfer for LVO stroke between July 2018 and March 2020. Time intervals and clinical outcomes were compared for 55 patients divided into pre- and post-Viz cohorts. RESULTS: The median initial door-to-neuroendovascular team (NT) notification time interval was significantly faster (25.0 min [IQR = 12.0] vs. 40.0 min [IQR = 61.0]; p = 0.01) with less variation (p < 0.05) following Viz LVO implementation. The median initial door-to-skin puncture time interval was 25 min shorter in the post-Viz cohort, although this was not statistically significant (p = 0.15). CONCLUSIONS: Preliminary results have shown that Viz LVO implementation is associated with earlier, more consistent NT notification times. This application can serve as an early warning system and a failsafe to ensure that no LVO is left behind.

Childhood ischaemic stroke in the basal ganglia can lead to fine motor and anxiety disorders: a retrospective analysis and follow-up of 109 cases.

BACKGROUND: Stroke in children easily causes long-term dysfunction. Whether the prognoses of motor and anxiety disorders are related to the affected stroke area has not been reported. METHODS: One hundred nine cases of children with ischaemic stroke were reviewed and divided into three groups: lenticular nucleus lesions only (lenticular nucleus group), lenticular nucleus and caudate head lesions (caudate head group), and lenticular nucleus and thalamus lesions (thalamus group). Overall prognosis was evaluated by the mRS score. The SCAS-P was used to evaluate anxiety in children aged ≥6 years. RESULTS: mRS scores were ≤ 2 points (mean: 0.62), no significant difference among groups. 3/21 (14.2%) patients in the caudate head group changed handedness, which is significantly higher than other groups. Patients with lesions in thalamus group had significantly higher SCAS-P scores. CONCLUSIONS: The overall prognosis of children with basal ganglia ischaemic stroke is good. However, hand preference changes and anxiety disorders may develop. Patients in the caudate head groups are more likely to suffer from fine motor disorders and changes in handedness. Patients within the thalamus group are more prone to anxiety than patients in the other groups. Anxiety disorders should be noted in children with basal ganglia stroke.

Functional connectivity of the retrosplenial cortex in rats with ischemic stroke is improved by electroacupuncture.

BACKGROUND: The aim of this study was to investigate the central mechanism underlying the putative beneficial effects of electroacupuncture (EA) on learning and memory ability of rats with ischemic stroke-induced cognitive deficits by resting-state functional magnetic resonance imaging (fMRI). METHODS: A rat model of middle cerebral artery occlusion (MCAO)-induced cognitive deficit (MICD) was established. Rats were randomly assigned into a sham-operated control group (SC group, n = 12), untreated MICD model group (MICD group, n = 12), and MICD group receiving EA treatment at GV20 and GV24 (MICD + EA group, n = 12). RESULTS: Compared to the MICD group, rats in the MICD + EA group receiving EA at GV20 and GV24 exhibited significantly shortened escape latency times and crossed the position of the platform a significantly increased number of times during the Morris water maze test on the 14th day after EA, which suggested EA could significantly improve spatial learning and memory ability. Furthermore, compared to the MICD group, functional connectivity of the left retrosplenial cortex (RSC) with the left hippocampus, left RSC, right RSC, left cingulate gyrus, right cingulate gyrus, right tegmentum of midbrain, and right visual cortex was increased in the MICD + EA group; the MICD group showed decreased functional connectivity of the left RSC with the left hippocampus, right hippocampus, left RSC, right RSC, right amygdaloid body, left visual cortex, and right visual cortex. CONCLUSION: These findings suggest that EA at GV20 and GV24 might improve the learning and memory ability of MICD rats by increasing the functional connectivity between the RSC and hippocampus, cingulate gyrus and midbrain, which is encouraging for the potential treatment for cognitive impairment secondary to ischemia stroke.

Electroacupuncture promotes motor function and functional connectivity in rats with ischemic stroke: an animal resting-state functional magnetic resonance imaging study.

BACKGROUND: To evaluate whether electroacupuncture (EA) treatment at LI11 and ST36 could reduce motor impairments and enhance brain functional recovery in a rat model of ischemic stroke. METHODS: A rat model of middle cerebral artery occlusion (MCAO) was established. EA at LI11 and ST36 was started at 24 h (MCAO + EA group) after ischemic stroke modeling. Untreated model (MCAO) and sham-operated (Sham) groups were included as controls. The neurological deficits of all groups were assessed using modified neurologic severity scores (mNSS) at 24 h and 14 days after MCAO. To further investigate the effect of EA on infarct volume and brain function, functional magnetic resonance imaging was used to estimate the size of the brain lesions and neural activities of each group at 14 days after ischemic stroke. RESULTS: EA treatment of MCAO rats led to a significant reduction in the infarct volumes accompanied by functional recovery, reflected in improved mNSS outcomes and motor functional performances. Furthermore, functional connectivity between the left motor cortex and left cerebellum posterior lobe, right motor cortex, left striatum and bilateral sensory cortex were decreased in MCAO group but increased after EA treatment. CONCLUSION: EA at LI11 and ST36 could enhance the functional connectivity between the left motor cortex and the motor function-related brain regions, including the motor cortex, sensory cortex and striatum, in rats. EA exhibits potential as a treatment for ischemic stroke.

Longitudinal multiparametric MRI study of hydrogen-enriched water with minocycline combination therapy in experimental ischemic stroke in rats.

Free radicals are downstream mediators of several cytotoxic cascades contributing to ischemic brain injury. Molecular hydrogen (H2) is an antioxidant potentially useful in the treatment of stroke. Hydrogen is easy to deliver, biologically non-toxic and diffuses freely through all biological structures including the blood-brain barrier and cellular membranes. This study evaluated the efficacy of hydrogen treatments in a rat stroke model compared to vehicle-treated controls using multiparametric MRI and neurological tests. Additionally, comparison of H2 treatment alone was made with H2 combined with minocycline (H2M) treatment (12 rats per group). The primary findings were: i) H2 therapy reduced infarct volume in both H2 and H2M groups compared to controls at 1 and 7 days after stroke, and ii) both H2 and H2M improved neurologic functional recovery on day 7. The secondary outcomes were: iii) H2M treatment attenuated post-stroke hyperperfusion in the hyperacute phase, and iv) H2M markedly minimized white matter injury. In conclusion, this is the first study to use MRI to longitudinally study H2 and H2M treatment on ischemic stroke and the first study to compare H2 treatment combined with another potential stroke therapeutic (H2M).

Ponatinib-induced ischemic stroke in larval zebrafish for drug screening.

Conventional mammalian ischemic stroke models for drug screening are technically challenging, laborious and time-consuming. In this study, using Ponatinib as an inducer, we developed and characterized a zebrafish ischemic stroke model. This zebrafish ischemic stroke had the cerebral vascular endothelial injury, thrombosis, reduced blood flow, inflammation and apoptosis as well as the reduced motility. The zebrafish ischemic stroke model was validated with 6 known human therapeutic drugs of ischemic stroke (Aspirin, Clopidogrel, Naoxintong capsules, Edaravone, Xingnaojing injection, Shuxuening injection). The mRNA levels of the neovascularization-related gene (vegfaa) and vascular endothelial growth factor receptor gene (VEGFR), neurodevelopment related genes (mbp and α1-tubulin), brain-derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF) were significantly downregulated; whereas apoptosis-related genes (caspase-3, caspase-7, caspase-9 and bax/bcl-2), and inflammatory factor genes (IL-1ß, IL-6, IL-10, TNF-α and NF-κB) were remarkably upregulated in the model. These results suggest that the pathophysiology of Ponatinib-induced zebrafish ischemic stroke is similar to that of human ischemic stroke patients and this whole animal model could be used to study the complex cellular and molecular pathogenesis of ischemic stroke and to rapidly identify therapeutic agents.

Characteristics of Recurrent Ischemic Stroke After Embolic Stroke of Undetermined Source: Secondary Analysis of a Randomized Clinical Trial.

Importance: The concept of embolic stroke of undetermined source (ESUS) unifies a subgroup of cryptogenic strokes based on neuroimaging, a defined minimum set of diagnostic tests, and exclusion of certain causes. Despite an annual stroke recurrence rate of 5%, little is known about the etiology underlying recurrent stroke after ESUS. Objective: To identify the stroke subtype of recurrent ischemic strokes after ESUS, to explore the interaction with treatment assignment in each category, and to examine the consistency of cerebral location of qualifying ESUS and recurrent ischemic stroke. Design, Setting, and Participants: The NAVIGATE-ESUS trial was a randomized clinical trial conducted from December 23, 2014, to October 5, 2017. The trial compared the efficacy and safety of rivaroxaban and aspirin in patients with recent ESUS (n = 7213). Ischemic stroke was validated in 309 of the 7213 patients by adjudicators blinded to treatment assignment and classified by local investigators into the categories ESUS or non-ESUS (ie, cardioembolic, atherosclerotic, lacunar, other determined cause, or insufficient testing). Five patients with recurrent strokes that could not be defined as ischemic or hemorrhagic in absence of neuroimaging or autopsy were excluded. Data for this secondary post hoc analysis were analyzed from March to June 2019. Interventions: Patients were randomly assigned to receive rivaroxaban, 15 mg/d, or aspirin, 100 mg/d. Main Outcomes and Measures: Association of recurrent ESUS with stroke characteristics. Results: A total of 309 patients (205 men [66%]; mean [SD] age, 68 [10] years) had ischemic stroke identified during the median follow-up of 11 (interquartile range [IQR], 12) months (annualized rate, 4.6%). Diagnostic testing was insufficient for etiological classification in 39 patients (13%). Of 270 classifiable ischemic strokes, 156 (58%) were ESUS and 114 (42%) were non-ESUS (37 [32%] cardioembolic, 26 [23%] atherosclerotic, 35 [31%] lacunar, and 16 [14%] other determined cause). Atrial fibrillation was found in 27 patients (9%) with recurrent ischemic stroke and was associated with higher morbidity (median change in modified Rankin scale score 2 [IQR, 3] vs 0 (IQR, 1]) and mortality (15% vs 1%) than other causes. Risk of recurrence did not differ significantly by subtype between treatment groups. For both the qualifying and recurrent strokes, location of infarct was more often in the left (46% and 54%, respectively) than right hemisphere (40% and 37%, respectively) or brainstem or cerebellum (14% and 9%, respectively). Conclusions and Relevance: In this secondary analysis of randomized clinical trial data, most recurrent strokes after ESUS were embolic and of undetermined source. Recurrences associated with atrial fibrillation were a minority but were more often disabling and fatal. More extensive investigation to identify the embolic source is important toward an effective antithrombotic strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT02313909.