Atrial Fibrillation In Patients With Stroke Attributed to Large- or Small-Vessel Disease: 3-Year Results From the STROKE AF Randomized Clinical Trial.

Importance: The STROKE AF study found that in patients with prior ischemic stroke attributed to large-artery atherosclerotic disease (LAD) or small-vessel occlusive disease (SVD), 12% developed AF over 1 year when monitored with an insertable cardiac monitor (ICM). The occurrence over subsequent years is unknown. Objectives: To compare the rates of AF detection through 3 years of follow-up between an ICM vs site-specific usual care in patients with prior ischemic stroke attributed to LAD or SVD. Design, Setting, and Participants: This multicenter, randomized (1:1) clinical trial took place at 33 sites in the US with enrollment between April 2016 and July 2019 and 3-year follow-up through July 2022. Eligible patients were aged 60 years or older, or aged 50 to 59 years with at least 1 additional stroke risk factor and had an index ischemic stroke attributed to LAD or SVD within 10 days prior to ICM insertion. Of the 496 patients enrolled, 492 were randomized and 4 were excluded. Interventions: ICM monitoring vs site-specific usual care. Main Outcomes and Measures: The prespecified long-term outcome of the trial was AF detection through study follow-up (up to 3 years). AF was defined as an episode lasting more than 30 seconds, adjudicated by an expert committee. Results: In total, 492 patients were randomized and included in the analyses (median [IQR] age, 66 [60-74] years; 307 men [62.4%] and 185 women [37.6%]), of whom 314 completed 3-year follow-up (63.8%). The incidence rate of AF at 3 years was 21.7% (46 patients) in the ICM group vs 2.4% (5 patients) in the control group (hazard ratio, 10.0; 95% CI, 4.0-25.2; P < .001). Conclusions and Relevance: Patients with ischemic stroke attributed to LAD or SVD face an increasing risk of AF over time and most of the AF occurrences are not reliably detected by standard medical monitoring methods. One year of negative monitoring should not reassure clinicians that patients who have experienced stroke will not develop AF over the next 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT02700945.

Mapping Lesion-Related Epilepsy to a Human Brain Network.

Importance: It remains unclear why lesions in some locations cause epilepsy while others do not. Identifying the brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions. Objective: To assess whether lesion locations associated with epilepsy map to specific brain regions and networks. Design, Setting, and Participants: This case-control study used lesion location and lesion network mapping to identify the brain regions and networks associated with epilepsy in a discovery data set of patients with poststroke epilepsy and control patients with stroke. Patients with stroke lesions and epilepsy (n = 76) or no epilepsy (n = 625) were included. Generalizability to other lesion types was assessed using 4 independent cohorts as validation data sets. The total numbers of patients across all datasets (both discovery and validation datasets) were 347 with epilepsy and 1126 without. Therapeutic relevance was assessed using deep brain stimulation sites that improve seizure control. Data were analyzed from September 2018 through December 2022. All shared patient data were analyzed and included; no patients were excluded. Main Outcomes and Measures: Epilepsy or no epilepsy. Results: Lesion locations from 76 patients with poststroke epilepsy (39 [51%] male; mean [SD] age, 61.0 [14.6] years; mean [SD] follow-up, 6.7 [2.0] years) and 625 control patients with stroke (366 [59%] male; mean [SD] age, 62.0 [14.1] years; follow-up range, 3-12 months) were included in the discovery data set. Lesions associated with epilepsy occurred in multiple heterogenous locations spanning different lobes and vascular territories. However, these same lesion locations were part of a specific brain network defined by functional connectivity to the basal ganglia and cerebellum. Findings were validated in 4 independent cohorts including 772 patients with brain lesions (271 [35%] with epilepsy; 515 [67%] male; median [IQR] age, 60 [50-70] years; follow-up range, 3-35 years). Lesion connectivity to this brain network was associated with increased risk of epilepsy after stroke (odds ratio [OR], 2.82; 95% CI, 2.02-4.10; P < .001) and across different lesion types (OR, 2.85; 95% CI, 2.23-3.69; P < .001). Deep brain stimulation site connectivity to this same network was associated with improved seizure control (r, 0.63; P < .001) in 30 patients with drug-resistant epilepsy (21 [70%] male; median [IQR] age, 39 [32-46] years; median [IQR] follow-up, 24 [16-30] months). Conclusions and Relevance: The findings in this study indicate that lesion-related epilepsy mapped to a human brain network, which could help identify patients at risk of epilepsy after a brain lesion and guide brain stimulation therapies.

Non-invasive brain stimulation effectively improves post-stroke sensory impairment: a systematic review and meta-analysis.

More than half of stroke patients experience sensory dysfunction that affects their quality of life. Previous training modalities are ineffective in improving sensory function. In contrast, non-invasive brain stimulation (NIBS) is a new promising intervention for stroke rehabilitation. The aim of this meta-analysis was to summarize the current effectiveness of NIBS in the treatment of post-stroke sensory dysfunction. Articles published in PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Chinese scientific journals full-text database (VIP), and Wanfang database from the inception to March 8, 2023 were searched. There were no restrictions on language. A total of 14 RCTs were included (combined n = 804). Moderate-quality evidence suggested that NIBS significantly improved sensory function after stroke, and significant effects were observed up to 1 year after the intervention. In subgroup analysis, treatment with transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS) was significantly more effective than controls for recovery of sensory function in stroke patients. Stimulation of the primary motor cortex (M1), primary somatosensory cortex (S1) or M1 + S1 stimulation sites significantly improved sensory function. NIBS for sensory dysfunction showed significant therapeutic potential in patients with different stages of stroke. No significant effects were observed in subjects with less than 10 NIBS stimulations. Significant therapeutic effects were observed with either high-frequency or low-frequency rTMS.

Virtual reality and motor imagery for early post-stroke rehabilitation.

BACKGROUND: Motor impairment is a common consequence of stroke causing difficulty in independent movement. The first month of post-stroke rehabilitation is the most effective period for recovery. Movement imagination, known as motor imagery, in combination with virtual reality may provide a way for stroke patients with severe motor disabilities to begin rehabilitation. METHODS: The aim of this study is to verify whether motor imagery and virtual reality help to activate stroke patients' motor cortex. 16 acute/subacute (< 6 months) stroke patients participated in this study. All participants performed motor imagery of basketball shooting which involved the following tasks: listening to audio instruction only, watching a basketball shooting animation in 3D with audio, and also performing motor imagery afterwards. Electroencephalogram (EEG) was recorded for analysis of motor-related features of the brain such as power spectral analysis in the [Formula: see text] and [Formula: see text] frequency bands and spectral entropy. 18 EEG channels over the motor cortex were used for all stroke patients. RESULTS: All results are normalised relative to all tasks for each participant. The power spectral densities peak near the [Formula: see text] band for all participants and also the [Formula: see text] band for some participants. Tasks with instructions during motor imagery generally show greater power spectral peaks. The p-values of the Wilcoxon signed-rank test for band power comparison from the 18 EEG channels between different pairs of tasks show a 0.01 significance of rejecting the band powers being the same for most tasks done by stroke subjects. The motor cortex of most stroke patients is more active when virtual reality is involved during motor imagery as indicated by their respective scalp maps of band power and spectral entropy. CONCLUSION: The resulting activation of stroke patient's motor cortices in this study reveals evidence that it is induced by imagination of movement and virtual reality supports motor imagery. The framework of the current study also provides an efficient way to investigate motor imagery and virtual reality during post-stroke rehabilitation.

Tratamientos agudos de recanalización en el ictus arterial isquémico pediátrico posnatal. Código ictus pediátrico / Acute recanalization treatments in postnatal paediatric ischaemic arterial strole. Paediatric stroke code

El ictus arterial isquémico infantil es una patología mucho menos conocida que en adultos debido a su menor frecuencia y a su diferente etiología. Sin embargo, es también una patología grave con una alta incidencia de secuelas severas y perennes, que sobrepasan el 50% de los casos. El manejo agudo del ictus arterial isquémico pediátrico posnatal (IAIPP) ha cambiado drásticamente en los últimos años, fundamentalmente en lo referente a los tratamientos de recanalización (trombólisis y terapias endovasculares). Estos tratamientos, que antes no se recomendaban en la edad infantil, se están afianzando cada vez más en la práctica diaria. Aunque los estudios realizados en niños no tienen un grado de evidencia alto por ser retrospectivos y porque el número de casos es bajo, soportan la idea de que dichos tratamientos son igual de seguros y eficaces que en los adultos siempre que se realicen con unos criterios de inclusión y exclusión determinados y dentro de un tiempo determinado desde el inicio de los síntomas (ventana terapéutica). En este artículo se revisa, a la luz de los conocimientos actuales, el manejo agudo del IAIPP. Debido a que la eficacia de estos tratamientos está íntimamente ligada al inicio precoz de los mismos, es necesaria la existencia de un código ictus infantil como ampliación del código ictus que se aplica a los adultos. Ha empezado a implantarse en España desde el año 2019 aunque todavía hay importantes zonas del país donde aún no se aplica. (AU)

In children, arterial ischemic stroke is a much less understood disease compared to in adults due to its lower frequency and different aetiology. However, it is also a serious disease, with a high incidence of severe and permanent sequelae that exceeds 50% of total cases. The acute management of postnatal arterial ischaemic stroke (MNAIS) has changed drastically in recent years, chiefly on account of recanalization treatments (thrombolysis and endovascular therapies). These treatments, which used to not be recommended in childhood, are increasingly implemented in everyday clinical practice. Although the evidence from studies carried out in children is not of high quality due to their retrospective design and the small number of reported cases, they support the hypothesis that these treatments are as safe and effective as they are in adults as long as appropriate eligibility criteria are applied and they are used within a certain time from the onset of symptoms (therapeutic window). This article reviews the MNAIS based on the current scientific evidence. Since the efficacy of these treatments is highly dependent on their early initiation, a paediatric stroke code needs to be in place as an extension of the stroke code applied to adults. It has started to be introduced in Spain since 2019, although there are still large areas of the country where it has yet to be applied. (AU)

Optimal Intensity and Duration of Walking Rehabilitation in Patients With Chronic Stroke: A Randomized Clinical Trial.

Importance: For walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization. Objective: To assess the optimal training intensity (vigorous vs moderate) and minimum training duration (4, 8, or 12 weeks) needed to maximize immediate improvement in walking capacity in patients with chronic stroke. Design, Setting, and Participants: This multicenter randomized clinical trial using an intent-to-treat analysis was conducted from January 2019 to April 2022 at rehabilitation and exercise research laboratories. Survivors of a single stroke who were aged 40 to 80 years and had persistent walking limitations 6 months or more after the stroke were enrolled. Interventions: Participants were randomized 1:1 to high-intensity interval training (HIIT) or moderate-intensity aerobic training (MAT), each involving 45 minutes of walking practice 3 times per week for 12 weeks. The HIIT protocol used repeated 30-second bursts of walking at maximum safe speed, alternated with 30- to 60-second rest periods, targeting a mean aerobic intensity above 60% of the heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40% of the HRR, progressing up to 60% of the HRR as tolerated. Main Outcomes and Measures: The main outcome was 6-minute walk test distance. Outcomes were assessed by blinded raters after 4, 8, and 12 weeks of training. Results: Of 55 participants (mean [SD] age, 63 [10] years; 36 male [65.5%]), 27 were randomized to HIIT and 28 to MAT. The mean (SD) time since stroke was 2.5 (1.3) years, and mean (SD) 6-minute walk test distance at baseline was 239 (132) m. Participants attended 1675 of 1980 planned treatment visits (84.6%) and 197 of 220 planned testing visits (89.5%). No serious adverse events related to study procedures occurred. Groups had similar 6-minute walk test distance changes after 4 weeks (HIIT, 27 m [95% CI, 6-48 m]; MAT, 12 m [95% CI, -9 to 33 m]; mean difference, 15 m [95% CI, -13 to 42 m]; P = .28), but HIIT elicited greater gains after 8 weeks (58 m [95% CI, 39-76 m] vs 29 m [95% CI, 9-48 m]; mean difference, 29 m [95% CI, 5-54 m]; P = .02) and 12 weeks (71 m [95% CI, 49-94 m] vs 27 m [95% CI, 3-50 m]; mean difference, 44 m [95% CI, 14-74 m]; P = .005) of training; HIIT also showed greater improvements than MAT on some secondary measures of gait speed and fatigue. Conclusions and Relevance: These findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In patients with chronic stroke, vigorous walking exercise produced significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks were needed to maximize immediate gains. Trial Registration: ClinicalTrials.gov Identifier: NCT03760016.

Exploratory Study on the Clinical use of EEG for the People with Chronic Stroke and Their Correlation with the Neuropsychological Outcome.

Objective. To measure the EEG signals of the people with chronic stroke in eyes-closed and eyes-open condition and study their relationship with the cognitive function and mental wellbeing. Methods. The investigators would conduct cognitive and mental wellbeing tests on recruited subjects. Their EEG signal was acquired by the 16-channel EEG system. The absolute power under different frequency bands and EEG indices (delta alpha ratio and pairwise derived brain symmetry index) in different eye conditions was calculated. Pearson's correlation was conducted to investigate the association between the clinical tests and the EEG index. Results. 32 subjects were recruited for the study. There was a significant correlation between the pairwise derived brain symmetry index (pdBSI) in eyes-open condition with the Stroop Test (p = .002), Paced Auditory Serial Addition Test-3 s (p = .008)/2 s (p = .002) and WHO-5 well-being scale (p = .023). Conclusions. There is a significant correlation between the brain symmetry index and the cognitive and wellbeing assessment. Brain symmetry index over the delta frequency has been found to be the most useful parameter relating to the clinical score.Significance:It is recommended to use EEG as an adjunctive neuropsychological assessment in clinics for people with chronic stroke, especially for clients who could not undertake conventional assessments (eg aphasia, attention problem).Highlights: There is a significant correlation between the EEG index and the clinical neuropsychological assessmentPairwise Derived Brain Symmetry index in delta frequency range correlated with most of the neuropsychological outcome.It is feasible for us to adopt EEG as an adjunctive assessment in clinical settings.

Poor collateral flow with severe hypoperfusion explains worse outcome in acute stroke patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with poorer functional outcomes in acute stroke patients. It has been hypothesized that this is due to poor collateral recruitment. AIMS: This study aimed to investigate the relationship between AF and collaterals with outcome in thrombectomy patients. METHODS: This retrospective cohort study identified 1036 acute ischemic patients from the INternational Stroke Perfusion Imaging REgistry. The cohort was divided into two groups: 432 with AF and 604 without AF. Patients were stratified by collateral grades as good, moderate, and poor. Within each collateral grade, the prediction of AF versus No AF for good outcome (3-month modified Rankin Scale of 0-2) was determined. Then, within each collateral grade, perfusion was compared between those with and without AF. RESULTS: AF was negatively associated with good outcome in patients with poor collaterals (26.7% vs 51.2% for AF vs No AF, odds ratio = 0.32 (95% confidence interval = 0.22-0.50), p < 0.001), but not in patients with good (50.9% vs 58.1% for AF vs No AF, odds ratio = 0.75 (0.46-1.23), p = 0.249) or moderate collaterals (43.6% vs 50.9% for AF vs No AF, odds ratio = 0.75 (0.47-1.18), p = 0.214). AF was associated with severe hypoperfusion only in patients with poor collateral flow (54.0 vs 35.5 mL for AF vs No AF, p < 0.001). CONCLUSIONS: AF-related stroke is associated with more severe hypoperfusion and worse outcome in those with poor collaterals.

Spatial neglect in the digital age: Influence of presentation format on patients' test behavior.

OBJECTIVE: Computerized neglect tests could significantly deepen our disorder-specific knowledge by effortlessly providing additional behavioral markers that are hardly or not extractable from existing paper-and-pencil versions. This study investigated how testing format (paper versus digital), and screen size (small, medium, large) affect the Center of cancelation (CoC) in right-hemispheric stroke patients in the Letters and the Bells cancelation task. Our second objective was to determine whether a machine learning approach could reliably classify patients with and without neglect based on their search speed, search distance, and search strategy. METHOD: We compared the CoC measure of right hemisphere stroke patients with neglect in two cancelation tasks across different formats and display sizes. In addition, we evaluated whether three additional parameters of search behavior that became available through digitization are neglect-specific behavioral markers. RESULTS: Patients' CoC was not affected by test format or screen size. Additional search parameters demonstrated lower search speed, increased search distance, and a more strategic search for neglect patients than for control patients without neglect. CONCLUSION: The CoC seems robust to both test digitization and display size adaptations. Machine learning classification based on the additional variables derived from computerized tests succeeded in distinguishing stroke patients with spatial neglect from those without. The investigated additional variables have the potential to aid in neglect diagnosis, in particular when the CoC cannot be validly assessed (e.g., when the test is not performed to completion).

Cortical reactivity to transcranial magnetic stimulation predicts risk of post-stroke delirium.

OBJECTIVE: Post-stroke delirium (PSD) is a frequent and with regard to outcome unfavorable complication in acute stroke. The neurobiological mechanisms predisposing to PSD remain poorly understood, and biomarkers predicting its risk have not been established. We tested the hypothesis that hypoexcitable or disconnected brain networks predispose to PSD by measuring brain reactivity to transcranial magnetic stimulation with electroencephalography (TMS-EEG). METHODS: We conducted a cross-sectional study in 33 acute stroke patients within 48 hours of stroke onset. Brain reactivity to single-pulse TMS of dorsolateral prefrontal cortex, primary motor cortex and superior parietal lobule of the right hemisphere was quantified by response intensity, effective connectivity, perturbational complexity index (PCIST), and natural frequency of the TMS-EEG response. PSD development was clinically tracked every 8 hours before and for 7 days following TMS-EEG. RESULTS: Fourteen patients developed PSD while 19 patients did not. The PSD group showed lower excitability, effective connectivity, PCIST and natural frequency compared to the non-PSD group. The maximum PCIST over all three TMS sites demonstrated largest classification accuracy with a ROC-AUC of 0.943. This effect was independent of lesion size, affected hemisphere and stroke severity. Maximum PCIST and maximum natural frequency correlated inversely with delirium duration. CONCLUSIONS: Brain reactivity to TMS-EEG can unravel brain network states of reduced excitability, effective connectivity, perturbational complexity and natural frequency that identify acute stroke patients at high risk for development of delirium. SIGNIFICANCE: Findings provide novel insight into the pathophysiology of pre-delirium brain states and may promote effective delirium prevention strategies in those patients at high risk.

Del laboratorio a la clínica en el ictus isquémico agudo. Modelos experimentales in vitro e in vivo / From the laboratory to the clinic in acute ischaemic stroke. In vitro and in vivo experimental models

Introducción: La enfermedad cerebrovascular es una de las principales causas de muerte, discapacidad y demencia en el mundo. La forma más frecuente de la enfermedad, el ictus isquémico, sólo tiene un fármaco disponible, el activador tisular del plasminógeno, y pocos pacientes pueden beneficiarse de esta terapia por los estrictos criterios de inclusión establecidos para su uso. Esta circunstancia hace crucial la búsqueda de nuevas formas de tratamiento para combatir las secuelas de la enfermedad, y para ello es necesario el desarrollo de nuevos modelos biomiméticos que permitan conocer mejor su evolución. Desarrollo: En esta revisión, actualizamos las plataformas y modelos más utilizados en los últimos años para estudiar la fisiopatología del ictus isquémico. Por un lado, repasamos las plataformas bi- y tridimensionales sobre las que se llevan a cabo los ensayos in vitro y, por otro lado, describimos los modelos experimentales in vivo más utilizados en la actualidad, así como las técnicas para evaluar el daño isquémico. Conclusiones: El desarrollo de buenos modelos experimentales tiene como fin último encontrar nuevas formas de tratamiento y, de esta manera, mejorar el pronóstico y la calidad de vida de los pacientes; por ello, es importante generar nuevos dispositivos in vitro y refinar más aún los modelos in vivo para hacer posible una buena traslación a la clínica.(AU)

Introduction: Cerebrovascular disease is one of the leading causes of death, disability and dementia around the world. For the most common form of the disease, ischaemic stroke, there is only one drug available, tissue plasminogen activator, and few patients can benefit from this therapy because of the strict inclusion criteria established for its use. This circumstance makes it crucial to search for new forms of treatment to combat the sequelae of the disease, and this requires the development of new biomimetic models that allow for a better understanding of its evolution. Development: In this review, we update the platforms and models most widely used in recent years to study the pathophysiology of ischaemic stroke. On the one hand, we review the two- and three-dimensional platforms on which in vitro assays are carried out and, on the other, we describe the most commonly used in vivo experimental models and techniques for assessing ischaemic damage. Conclusions: The ultimate aim of developing good experimental models is to find new forms of treatment and thus improve patients’ prognosis and quality of life. It is therefore important to generate new in vitro devices and to further refine in vivo models to enable a good clinical translation.(AU)

Deep Convolution Generative Adversarial Network-Based Electroencephalogram Data Augmentation for Post-Stroke Rehabilitation with Motor Imagery.

The motor imagery brain-computer interface (MI-BCI) system is currently one of the most advanced rehabilitation technologies, and it can be used to restore the motor function of stroke patients. The deep learning algorithms in the MI-BCI system require lots of training samples, but the electroencephalogram (EEG) data of stroke patients is quite scarce. Therefore, the expansion of EEG data has become an important part of stroke clinical rehabilitation research. In this paper, a deep convolution generative adversarial network (DCGAN) model is proposed to generate artificial EEG data and further expand the scale of the stroke dataset. First, multichannel one-dimensional EEG data is converted into a two-dimensional EEG spectrogram using EEG2Image based on the modified S-transform. Then, DCGAN is used to artificially generate EEG data based on MI. Finally, the validity of the generated artificial EEG data is proved. This paper preliminarily indicates that generating artificial stroke data is a promising strategy, which contributes to the further development of stroke clinical rehabilitation.