Detangling the Structural Neural Correlates Associated with Resting versus Dynamic Phantom Limb Pain Intensity Using a Voxel-based Morphometry Analysis.

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.

Ipsilateral Nonstenotic Carotid Disease in Minor Ischemic Stroke: an Exploratory Analysis of The POINT Randomized Clinical Trial.

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.

Validating Existing Scales for Identification of Acute Stroke in an Inpatient Setting.

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 × 109 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.

Management dilemmas in acute ischemic stroke and concomitant acute pulmonary embolism: Case series and literature review.

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.

Safer Stroke-Dx Instrument: Identifying Stroke Misdiagnosis in the Emergency Department.

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.

Real-time Video Projection in an MRI for Characterization of Neural Correlates Associated with Mirror Therapy for Phantom Limb Pain.

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.

SSRI and Motor Recovery in Stroke: Reestablishment of Inhibitory Neural Network Tonus.

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.