Search

Background Early prediction of functional outcome after rtPA helps clinicians in prognostic conversations with stroke patients and their families. Three prognostic tools have been developed in this regard: DRAGON, MRI-DRAGON, and S-TPI scales. These tools, all performing with a comparable accuracy, have been internally and externally validated in tertiary care centers. However, their performance in rural areas remains uncertain. This study addresses this gap in the literature by evaluating the effectiveness of those prognostic tools in stroke patients treated in a rural area of the Midwest. Methods We conducted a retrospective study of stroke patients treated with thrombolytics at Southern Illinois Healthcare Stroke Network from July 2017 to June 2024. Data on demographics, clinical presentations, laboratory values, neuroimaging, and stroke metrics were collected. modified Rankin Scale (mRS) at one month, classified into good (mRS ≤2) and poor (mRS ≥5) outcomes was noted. DRAGON and MRI-DRAGON scores were calculated. S-TPI model was built. Area under the receiver operating characteristic curve (AUC) with its 95% confidence interval was calculated for each prognostic model. Results A total of 279 patients were included in this study. Of those, 43% (n=119) were male. Median age (IQR) was 69 (57-80) years. NIHSS at presentation (IQR) was 7 (4-13). 12% of the cohort (n=34) had posterior circulation stroke. At one month, 66% of patients (n=185) had mRS≤2, whereas 14% of patients (n=39) mRS≥5. MRI-DRAGON showed the highest accuracy in predicting both good (AUC=0.86, 95%CI:0.81-0.90) and poor outcomes (AUC=0.84, 95%CI:0.76-0.91). DRAGON also demonstrated high accuracy for good (AUC=0.85, 95%CI:0.80 -0.89) and poor (AUC=0.82, 95%CI:0.75-0.90) outcomes. Conversely, in our population, the S-TPI model had the lowest accuracy for good (AUC=0.56, 95%CI:0.49-0.63) and poor (AUC=0.68, 95%CI:0.61-0.76) outcomes. Conclusions Among the available grading scores, MRI-DRAGON score can be considered the more accurate short-term prognostic tool for stroke patients treated with rtPA in the rural setting., (The Author(s). Published by S. Karger AG, Basel.)

Introduction and Problem Statement: The Neurocritical Care (NCC) Society Resident and Fellow Task Force's NEURON study concluded that learners had significant concerns regarding the need for educational improvement in NCC. To address these shortcomings, we identified the lack of an educational curriculum for trainees in NCC and developed a Twitter-based educational curriculum for trainees to improve knowledge in NCC., Objectives: The objectives of this study were to describe the pathophysiology, delineate a systematic diagnostic approach, and apply evidence-based strategies in the management of diseases in NCC., Methods and Curriculum Description: Ten trainees developed a Tweetorial (educational content available on Twitter)-based curriculum, with individual review by at least 2 NCC faculty. Learners were recruited through Twitter and randomized to 1 of 2 groups in a wait-list control prospective study. Group 1 completed the curriculum in the first 6 months of the 2021-2022 academic year, and group 2 completed the curriculum in the second half. Tweetorials were posted weekly on a private Twitter account only available to the active learner group. Learners were assessed by a multiple-choice format test (written by the trainees and reviewed by faculty) at 3 time points: before the first Tweetorial was released (preeducational curriculum assessment), after group 1 completed all tutorials and before group 2 started the curriculum (assessment 1), and after both groups finished (assessment 2). The primary outcome was the mean score on the second and third assessments., Results and Assessment Data: One hundred forty-six learners were assigned to group 1 or 2 using stratified block randomization including 99 (68%) Neurology residents, 81 (55%) US-based. Each group was composed of 73 participants. A total of 20 Tweetorials were published on a private Twitter account (@NeurocriticalE). Completed assessments were obtained from 100, 32, and 18 learners for the pre-educational curriculum assessment, assessment 1, and assessment 2, respectively. Group 1 and group 2 performed similarly in the pre-educational curriculum assessment. A potential for knowledge improvement was observed in group 1 at assessments 1 and 2 when compared with the learner group 2. Group 1 had more impressions, engagements, likes, URL clicks, and media views., Discussion and Lessons Learned: Although there was some learner attrition, our study demonstrates that social media can effectively deliver educational content and engage a diverse group of trainees around the globe., Competing Interests: The authors report no disclosures relevant to the manuscript. Go to Neurology.org/NE for full disclosures., (© 2023 American Academy of Neurology.)

The management of phantom limb pain (PLP) is still challenging due to a partial understanding of its neurophysiological mechanisms. Structural neuroimaging features are potential biomarkers. However, only a few studies assessed their correlations with clinical severity and treatment response. This study aims to explore the association between brain gray matter volume (GMV) with phantom limb manifestations severity and PLP improvement after neuromodulatory treatments (transcranial direct current stimulation and mirror therapy). Voxel-based morphometry analyses and functional decoding using a reverse inference term-based meta-analytic approach were used. We included 24 lower limb traumatic amputees with moderate to severe PLP. We found that alterations of cortical GMV were correlated with PLP severity but not with other clinical manifestations. Less PLP severity was associated with larger brain clusters GMV in the non-affected prefrontal, insula (non-affected mid-anterior region), and bilateral thalamus. However, only the insula cluster survived adjustments. Moreover, the reverse inference meta-analytic approach revealed that the found insula cluster is highly functionally connected to the contralateral insula and premotor cortices, and the decoded psychological processes related to this cluster were "rating," "sustained attention," "impulsivity, " and "suffering." Moreover, we found that responders to neuromodulatory treatment have higher GMV in somatosensory areas (total volume of S1 and S2) in the affected hemisphere at baseline, compared to non-responders, even after adjustments., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: A significant proportion of strokes occur while patients are hospitalized for other reasons. Numerous stroke scales have been developed and validated for use in pre-hospital and emergency department settings, and there is growing interest to adapt these scales for use in the inpatient setting. We aimed to validate existing stroke scales for inpatient stroke codes., Methods: We retrospectively reviewed charts from inpatient stroke code activations at an urban academic medical center from January 2016 through December 2018. Receiver operating characteristic analysis was performed for each specified stroke scale including NIHSS, FAST, BE-FAST, 2CAN, FABS, TeleStroke Mimic, and LAMS. We also used logistic regression to identify independent predictors of stroke and to derive a novel scale., Results: Of the 958 stroke code activations reviewed, 151 (15.8%) had a final diagnosis of ischemic or hemorrhagic stroke. The area under the curve (AUC) of existing scales varied from .465 (FABS score) to .563 (2CAN score). Four risk factors independently predicted stroke: (1) recent cardiovascular procedure, (2) platelet count less than 50 × 10 9 per liter, (3) gaze deviation, and (4) presence of unilateral leg weakness. Combining these 4 factors into a new score yielded an AUC of .653 (95% confidence interval [CI] .604-.702)., Conclusion: This study suggests that currently available stroke scales may not be sufficient to differentiate strokes from mimics in the inpatient setting. Our data suggest that novel approaches may be required to help with diagnosis in this unique population., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Missed or delayed diagnosis of acute stroke, or false-negative stroke (FNS), at initial emergency department (ED) presentation occurs in ≈9% of confirmed stroke patients. Failure to rapidly diagnose stroke can preclude time-sensitive treatments, resulting in higher risks of severe sequelae and disability. In this study, we developed and tested a modified version of a structured medical record review tool, the Safer Dx Instrument, to identify FNS in a subgroup of hospitalized patients with stroke to gain insight into sources of ED stroke misdiagnosis., Methods: We conducted a retrospective cohort study at 2 unaffiliated comprehensive stroke centers. In the development and confirmatory cohorts, we applied the Safer Stroke-Dx Instrument to report the prevalence and documented sources of ED diagnostic error in FNS cases among confirmed stroke patients upon whom an acute stroke was suspected by the inpatient team, as evidenced by stroke code activation or urgent neurological consultation, but not by the ED team. Inter-rater reliability and agreement were assessed using interclass coefficient and kappa values (κ)., Results: Among 183 cases in the development cohort, the prevalence of FNS was 20.2% (95% CI, 15.0-26.7). Too narrow a differential diagnosis and limited neurological examination were common potential sources of error. The interclass coefficient for the Safer Stroke-Dx Instrument items ranged from 0.42 to 0.91, and items were highly correlated with each other. The κ for diagnostic error identification was 0.90 (95% CI, 0.821-0.978) using the Safer Stroke-Dx Instrument. In the confirmatory cohort of 99 cases, the prevalence of FNS was 21.2% (95% CI, 14.2-30.3) with similar sources of diagnostic error identified., Conclusions: Hospitalized patients identified by stroke codes and requests for urgent neurological consultation represent an enriched population for the study of diagnostic error in the ED. The Safer Stroke-Dx Instrument is a reliable tool for identifying FNS and sources of diagnostic error.

Background: Pulmonary embolism (PE) and acute ischemic stroke (AIS) are common disorders with high morbidity and mortality, rarely presenting simultaneously. There is a paucity of data regarding the management of this uncommon presentation. The treatment of these two entities is complex in the acute phase due to the concomitant need for thrombolysis in AIS and anticoagulation for PE., Methods: We retrospectively reviewed confirmed ischemic stroke cases to identify patients presented with simultaneous PE from June 2018 to May 2019. Additionally, a literature review was performed. Two reviewers assessed the manuscripts' quality, and relevant data regarding clinical course and management was extracted., Results: We reviewed 439 patient charts, identifying two cases of concomitant AIS and PE. Additionally, twelve articles (n = 15 subjects) fulfilled our literature review criteria for a total of 17 cases, including ours. Intravenous anticoagulation (70.5%) was the most frequent intervention targeting both disorders. Therapies such as intravenous thrombolysis (23.53% (n = 4)) and mechanical thrombectomy (23.53% (n = 4)) were specific in AIS. Catheter-directed thrombolysis (5.88%) was used for PE. Clinical outcomes were favorable (asymptomatic or mild disable symptoms) in 47.05% (N = 8) of patients, while 41.17% had poor outcomes (severe disable symptoms or death)., Conclusions: AIS and PE stand for a challenge when they present simultaneously. The evaluation of risks and benefits of therapies such as intravenous thrombolysis, mechanical thrombectomy, and catheter-directed-thrombolysis in the clinical context is essential. According to our review, the ischemic stroke burden guides systemic anticoagulation decisions over interventional procedures when the hemodynamic status remains unaffected., (© 2021 The Authors.)

Background and Purpose: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with stroke. The role of sex on stroke outcome has not been investigated. To objective of this paper is to describe the characteristics of a diverse cohort of acute stroke patients with COVID-19 disease and determine the role of sex on outcome., Methods: This is a retrospective study of patients with acute stroke and SARS-CoV-2 infection admitted between March 15 to May 15, 2020 to one of the six participating comprehensive stroke centers. Baseline characteristics, stroke subtype, workup, treatment and outcome are presented as total number and percentage or median and interquartile range. Outcome at discharge was determined by the modified Rankin Scale Score (mRS). Variables and outcomes were compared for males and females using univariate and multivariate analysis., Results: The study included 83 patients, 47% of which were Black, 28% Hispanics/Latinos, and 16% whites. Median age was 64 years. Approximately 89% had at least one preexisting vascular risk factor (VRF). The most common complications were respiratory failure (59%) and septic shock (34%). Compared with females, a higher proportion of males experienced severe SARS-CoV-2 symptoms requiring ICU hospitalization (73% vs. 49%; p = 0.04). When divided by stroke subtype, there were 77% ischemic, 19% intracerebral hemorrhage and 3% subarachnoid hemorrhage. The most common ischemic stroke etiologies were cryptogenic (39%) and cardioembolic (27%). Compared with females, males had higher mortality (38% vs. 13%; p = 0.02) and were less likely to be discharged home (12% vs. 33%; p = 0.04). After adjustment for age, race/ethnicity, and number of VRFs, mRS was higher in males than in females (OR = 1.47, 95% CI = 1.03-2.09)., Conclusion: In this cohort of SARS-CoV-2 stroke patients, most had clinical evidence of coronavirus infection on admission and preexisting VRFs. Severe in-hospital complications and worse outcomes after ischemic strokes were higher in males, than females., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aim: Ipsilateral nonstenotic carotid disease is increasingly recognized as an etiology of ischemic stroke, however tailored treatment strategies are lacking. We aimed to examine clinical characteristics and treatment effects in patients with minor ischemic stroke associated with ipsilateral nonstenotic carotid disease in the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial., Methods: We performed an exploratory analysis of the interaction of the treatment effects of aspirin plus clopidogrel versus aspirin monotherapy, stratified by presence of ipsilateral nonstenotic carotid disease in patients with minor ischemic stroke in the POINT trial., Results: For this exploratory analysis, 167 patients presenting with ischemic stroke and ipsilateral nonstenotic carotid disease, defined as 1%-49% carotid stenosis ipsilateral to the corresponding territory of ischemic stroke, and 833 patients no carotid disease were included. Compared to patients with no carotid disease, patients with ipsilateral nonstenotic carotid disease were older (68.5 ± 11.3 years versus 61.3 ± 12.8 years; P < 0.001), and had a higher prevalence of hypertension (76.6% versus 59.2%, P < 0.001), ischemic heart disease (13.8% versus 5.4%, P < 0.001), and tobacco use (past: 34.1% versus 25.2%, P = 0.005; present: 27.5% versus 22.8%, P = 0.005). 5.4% of patients with ipsilateral nonstenotic carotid disease had recurrent ischemic stroke within 14 days. Patients receiving dual antiplatelet therapy had a numerical reduction in recurrent ischemic stroke compared to patients receiving aspirin monotherapy, however the exploratory analysis was underpowered to detect a statistically significant difference in treatment effect (HR 0.50, 95% CI 0.18-1.40, P = 0.19)., Conclusion: Patients with minor ischemic stroke and ipsilateral nonstenotic carotid disease had a high risk of early stroke recurrence in the POINT trial. Dual antiplatelet therapy provided a non-statistically significant reduction in recurrent ischemic stroke with no difference in safety outcomes compared to aspirin monotherapy. Further study is needed to determine if early and short duration dual antiplatelet therapy is beneficial for all patients with ipsilateral nonstenotic carotid disease., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Inc.)

The neural mechanism of phantom limb pain (PLP) is related to the intense brain reorganization process implicating plasticity after deafferentation mostly in sensorimotor system. There is a limited understanding of the association between the sensorimotor system and PLP. We used a novel task-based functional magnetic resonance imaging (fMRI) approach to (1) assess neural activation within a-priori selected regions-of-interested (motor cortex [M1], somatosensory cortex [S1], and visual cortex [V1]), (2) quantify the cortical representation shift in the affected M1, and (3) correlate these changes with baseline clinical characteristics. In a sample of 18 participants, we found a significantly increased activity in M1 and S1 as well as a shift in motor cortex representation that was not related to PLP intensity. In an exploratory analyses (not corrected for multiple comparisons), they were directly correlated with time since amputation; and there was an association between increased activity in M1 with a lack of itching sensation and V1 activation was negatively correlated with PLP. Longer periods of amputation lead to compensatory changes in sensory-motor areas; and itching seems to be a protective marker for less signal changes. We confirmed that PLP intensity is not associated with signal changes in M1 and S1 but in V1., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

There are multiple available treatments to enhance stroke rehabilitation, although few interventions have confirmed significant clinical improvements on motor function in pivotal Randomized Clinical Trials. Development of large Randomized Clinical Trials is limited by several barriers and low enrollment rate is considered an important factor. Consequently, most of the evidence comes from small sample size studies, often leading to limited conclusions. According to the National Institute of Health (NIH), about 80% of clinical trials in the United States do not achieve their timelines, increasing research costs and postponing regulatory approval of new therapies. Given that the success of a Randomized Clinical Trial is dependent on enrolling an adequate number of subjects, effective strategies to enhance recruitment rates are highly desirable. In addition, given the resources and time limitations, it is important to understand which strategies are most cost-effective. In this manuscript, we summarize and discuss nine recruitment strategies used in an NIH R21 sponsored clinical trial, including medical records review and online advertising, among others. In addition, we developed an index to compare the time spent benefit of each approach and guide the allocation of the recruitment efforts. For this trial, online advertising and referral from health care professionals other than physicians were the strategies with greater time-benefit, leading to the largest number of stroke subjects enrolled.

Mirror therapy (MT) has been proposed as an effective rehabilitative strategy to alleviate pain symptoms in amputees with phantom limb pain (PLP). However, establishing the neural correlates associated with MT therapy have been challenging given that it is difficult to administer the therapy effectively within a magnetic resonance imaging (MRI) scanner environment. To characterize the functional organization of cortical regions associated with this rehabilitative strategy, we have developed a combined behavioral and functional neuroimaging protocol that can be applied in participants with a leg amputation. This novel approach allows participants to undergo MT within the MRI scanner environment by viewing real-time video images captured by a camera. The images are viewed by the participant through a system of mirrors and a monitor that the participant views while lying on the scanner bed. In this manner, functional changes in cortical areas of interest (e.g., sensorimotor cortex) can be characterized in response to the direct application of MT.

Selective serotonin reuptake inhibitors (SSRIs) are currently widely used in the field of the neuromodulation not only because of their anti-depressive effects but also due to their ability to promote plasticity and enhance motor recovery in patients with stroke. Recent studies showed that fluoxetine promotes motor recovery after stroke through its effects on the serotonergic system enhancing motor outputs and facilitating long term potentiation, key factors in motor neural plasticity. However, little is known in regards of the exact mechanisms underlying these effects and several aspects of it remain poorly understood. In this manuscript, we discuss evidence supporting the hypothesis that SSRIs, and in particular fluoxetine, modulate inhibitory pathways, and that this modulation enhances reorganization and reestablishment of excitatory-inhibitory control; these effects play a key role in learning induced plasticity in neural circuits involved in the promotion of motor recovery after stroke. This discussion aims to provide important insights and rationale for the development of novel strategies for stroke motor rehabilitation.

Background: We hypothesized in this study that transcranial direct current stimulation (tDCS) of primary motor cortex could exert top-down modulation over subcortical systems associated with autonomic control and thus be useful to revert some of the dysfunctional changes found in the autonomic nervous system (ANS) of subjects with spinal cord injuries (SCI)., Objective: To explore the acute effect of tDCS on ANS indexed by Heart Rate Variability (HRV) in individuals with SCI and analyze whether this effect depends on the gender, degree, level and time of injury., Methods: In this randomized, placebo-controlled, crossover, double-blinded study, 18 adults with SCI (32.9±7.9 years old) were included; the intervention consisted of a single 12-minute session of active tDCS (anodal, 2 mA) and a control session of sham tDCS applied over Cz (bihemispheric motor cortex). HRV was calculated using spectral analysis. Low-frequency (LF), high-frequency (HF), and LF/HF ratio variables were evaluated before, during, and post tDCS., Results: A two-way repeated measures ANOVA showed that after active (anodal) stimulation, LF/HF ratio was significantly increased (P = 0.013). There was a trend for an interaction between time and stimulation for both LF and HF (P = 0.052). Paired exploratory t-tests reported effects on the difference of time [post-pre] between stimulation conditions for LF (P = 0.052), HF (P = 0.052) and LF/HF (P = 0.003)., Conclusion: Anodal tDCS of the motor cortex modulated ANS activity in individuals with SCI independent of gender, type and time of lesion. These changes were in the direction of normalization of ANS parameters, thus confirming our initial hypothesis that an enhancement of cortical excitability by tDCS could at least partially restore some of the dysfunctional activity in the ANS system of subjects with SCI.

Background: Despite the multiple available pharmacological and behavioral therapies for the management of chronic phantom limb pain (PLP) in lower limb amputees, treatment for this condition is still a major challenge and the results are mixed. Given that PLP is associated with maladaptive brain plasticity, interventions that promote cortical reorganization such as non-invasive brain stimulation and behavioral methods including transcranial direct current stimulation (tDCS) and mirror therapy (MT), respectively, may prove to be beneficial to control pain in PLP. Due to its complementary effects, a combination of tDCS and MT may result in synergistic effects in PLP., Objective: The objective of this study is to evaluate the efficacy of tDCS and MT as a rehabilitative tool for the management of PLP in unilateral lower limb amputees., Methods: A prospective, randomized, placebo-controlled, double-blind, factorial, superiority clinical trial will be carried out. Participants will be eligible if they meet the following inclusion criteria: lower limb unilateral traumatic amputees that present PLP for at least 3 months after the amputated limb has completely healed. Participants (N=132) will be randomly allocated to the following groups: (1) active tDCS and active MT, (2) sham tDCS and active MT, (3) active tDCS and sham MT, and (4) sham tDCS and sham MT. tDCS will be applied with the anodal electrode placed over the primary motor cortex (M1) contralateral to the amputation side and the cathode over the contralateral supraorbital area. Stimulation will be applied at the same time of the MT protocol with the parameters 2 mA for 20 minutes. Pain outcome assessments will be performed at baseline, before and after each intervention session, at the end of MT, and in 2 follow-up visits. In order to assess cortical reorganization and correlate with clinical outcomes, participants will undergo functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) before and after the intervention., Results: This clinical trial received institutional review board (IRB) approval in July of 2015 and enrollment started in December of 2015. To date 2 participants have been enrolled. The estimate enrollment rate is about 30 to 35 patients per year; thus we expect to complete enrollment in 4 years., Conclusions: This factorial design will provide relevant data to evaluate whether tDCS combined with MT is more effective than each therapy alone, as well as with no intervention (sham/sham) in patients with chronic PLP after unilateral lower limb amputation. In addition, this randomized clinical trial will help to investigate the neurophysiological mechanisms underlying the disease, which could potentially provide relevant findings for further management of this chronic condition and also help to optimize the use of this novel intervention., Trial Registration: Clinicaltrials.gov NCT02487966; https://clinicaltrials.gov/ct2/show/NCT02487966 (Archived by WebCite at http://www.webcitation.org/6i3GrKMyf).