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Patent foramen ovale (PFO) and atrial septal defects (ASDs) are two types of interatrial communications with unique clinical presentations and management strategies. The PFO is a normal part of fetal development that typically closes shortly after birth but may persist in as many as 25% to 30% of adults. The communication between atria may result in paradoxic embolism and embolic stroke. On the other hand, ASDs (anatomically defined as secundum, primum, sinus venosus, and coronary sinus in order of prevalence) typically result in right heart volume overload and are often associated with other congenital defects. The diagnostic methods, treatment options including surgical and percutaneous approaches, and potential complications are described. Both conditions underline the significance of precise diagnosis and appropriate management to mitigate risks and ensure optimal patient outcomes., Competing Interests: Disclosure C.H. Lin is a proctor for Abbott., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study was undertaken to examine averted stroke in optimized stroke systems., Methods: This secondary analysis of a multicenter trial from 2014 to 2020 compared patients treated by mobile stroke unit (MSU) versus standard management. The analytical cohort consisted of participants with suspected stroke treated with intravenous thrombolysis. The main outcome was a tissue-defined averted stroke, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis and no acute infarction/hemorrhage on imaging. An additional outcome was stroke with early symptom resolution, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis., Results: Among 1,009 patients with a median last known well to thrombolysis time of 87 minutes, 159 (16%) had tissue-defined averted stroke and 276 (27%) had stroke with early symptom resolution. Compared with standard management, MSU care was associated with more tissue-defined averted stroke (18% vs 11%, adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.13-2.98) and stroke with early symptom resolution (31% vs 21%, aOR = 1.74, 95% CI = 1.12-2.61). The relationships between thrombolysis treatment time and averted/early recovered stroke appeared nonlinear. Most models indicated increased odds for stroke with early symptom resolution but not tissue-defined averted stroke with earlier treatment. Additionally, younger age, female gender, hyperlipidemia, lower National Institutes of Health Stroke Scale, lower blood pressure, and no large vessel occlusion were associated with both tissue-defined averted stroke and stroke with early symptom resolution., Interpretation: In optimized stroke systems, 1 in 4 patients treated with thrombolysis recovered within 24 hours and 1 in 6 had no demonstrable brain injury on imaging. ANN NEUROL 2024;95:347-361., (© 2023 American Neurological Association.)

Mutations in Cullin-3 (Cul3), a conserved gene encoding a ubiquitin ligase, are strongly associated with autism spectrum disorder (ASD). Here, we characterize ASD-related pathologies caused by neuron-specific Cul3 knockdown in Drosophila. We confirmed that neuronal Cul3 knockdown causes short sleep, paralleling sleep disturbances in ASD. Because sleep defects and ASD are linked to metabolic dysregulation, we tested the starvation response of neuronal Cul3 knockdown flies; they starved faster and had lower triacylglyceride levels than controls, suggesting defects in metabolic homeostasis. ASD is also characterized by increased biomarkers of oxidative stress; we found that neuronal Cul3 knockdown increased sensitivity to hyperoxia, an exogenous oxidative stress. Additional hallmarks of ASD are deficits in social interactions and learning. Using a courtship suppression assay that measures social interactions and memory of prior courtship, we found that neuronal Cul3 knockdown reduced courtship and learning compared to controls. Finally, we found that neuronal Cul3 depletion alters the anatomy of the mushroom body, a brain region required for memory and sleep. Taken together, the ASD-related phenotypes of neuronal Cul3 knockdown flies establish these flies as a genetic model to study molecular and cellular mechanisms underlying ASD pathology, including metabolic and oxidative stress dysregulation and neurodevelopment., (© 2024. The Author(s).)

Background: Few data exist on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials. A recent trial of mobile stroke units (MSUs) demonstrated faster treatment and improved outcomes, and included PD patients., Aim: To determine outcomes with tissue plasminogen activator (tPA), and benefit of MSU versus management by emergency medical services (EMS), for PD patients., Methods: Primary outcomes were utility-weighted modified Rankin Scale (uw-mRS). Linear and logistic regression models compared outcomes in patients with versus without PD, and PD patients treated by MSU versus standard management by EMS. Time metrics, safety, quality of life, and health-care utilization were compared., Results: Of the 1047 tPA-eligible ischemic stroke patients, 254 were with PD (baseline mRS 2-5) and 793 were without PD (baseline mRS 0-1). Although PD patients had worse 90-day uw-mRS, higher mortality, more health-care utilization, and worse quality of life than non-disabled patients, 53% returned to at least their baseline mRS, those treated faster had better outcome, and there was no increased bleeding risk. Comparing PD patients treated by MSU versus EMS, 90-day uw-mRS was 0.42 versus 0.36 (p = 0.07) and 57% versus 46% returned to at least their baseline mRS. There was no interaction between disability status and MSU versus EMS group assignment (p = 0.67) for 90-day uw-mRS., Conclusion: PD did not prevent the benefit of faster treatment with tPA in the BEST-MSU study. Our data support inclusion of PD patients in the MSU management paradigm., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.C. Grotta has received grants from Patient-Centered Outcomes Research Institute (PCORI), NIH, Genentech, CSL Behring, and Chiesi; is a consultant for Frazer, advison the scientific advisory board for Haemonetics and Acticor, and on the DSMB for Prolong Pharma. J.L. Saver receives contracted hourly payments from Bayer, Biogen, Roche, Genentech, Medtronic, Novo Nordisk, and Occlutech for service on clinical trial steering committees and DSMBs. The remaining authors have no disclosures.

Stroke is one of the leading causes of death and disability in the world. Despite intensive research on automatic stroke lesion segmentation from non-invasive imaging modalities including diffusion-weighted imaging (DWI), challenges remain such as a lack of sufficient labeled data for training deep learning models and failure in detecting small lesions. In this paper, we propose BBox-Guided Segmentor, a method that significantly improves the accuracy of stroke lesion segmentation by leveraging expert knowledge. Specifically, our model uses a very coarse bounding box label provided by the expert and then performs accurate segmentation automatically. The small overhead of having the expert provide a rough bounding box leads to large performance improvement in segmentation, which is paramount to accurate stroke diagnosis. To train our model, we employ a weakly-supervised approach that uses a large number of weakly-labeled images with only bounding boxes and a small number of fully labeled images. The scarce fully labeled images are used to train a generator segmentation network, while adversarial training is used to leverage the large number of weakly-labeled images to provide additional learning signals. We evaluate our method extensively using a unique clinical dataset of 99 fully labeled cases (i.e., with full segmentation map labels) and 831 weakly labeled cases (i.e., with only bounding box labels), and the results demonstrate the superior performance of our approach over state-of-the-art stroke lesion segmentation models. We also achieve competitive performance as a SOTA fully supervised method using less than one-tenth of the complete labels. Our proposed approach has the potential to improve stroke diagnosis and treatment planning, which may lead to better patient outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Inhibitors of enzymes that inactivate amine neurotransmitters (dopamine, serotonin), such as catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), are thought to increase neurotransmitter levels and are widely used to treat Parkinson's disease and psychiatric disorders, yet the role of these enzymes in regulating behavior remains unclear. Here, we investigated the genetic loss of a similar enzyme in the model organism Drosophila melanogaster. Because the enzyme Ebony modifies and inactivates amine neurotransmitters, its loss is assumed to increase neurotransmitter levels, increasing behaviors such as aggression and courtship and decreasing sleep. Indeed, ebony mutants have been described since 1960 as "aggressive mutants," though this behavior has not been quantified. Using automated machine learning-based analyses, we quantitatively confirmed that ebony mutants exhibited increased aggressive behaviors such as boxing but also decreased courtship behaviors and increased sleep. Through tissue-specific knockdown, we found that ebony's role in these behaviors was specific to glia. Unexpectedly, direct measurement of amine neurotransmitters in ebony brains revealed that their levels were not increased but reduced. Thus, increased aggression is the anomalous behavior for this neurotransmitter profile. We further found that ebony mutants exhibited increased aggression only when fighting each other, not when fighting wild-type controls. Moreover, fights between ebony mutants were less likely to end with a clear winner than fights between controls or fights between ebony mutants and controls. In ebony vs. control fights, ebony mutants were more likely to win. Together, these results suggest that ebony mutants exhibit prolonged aggressive behavior only in a specific context, with an equally dominant opponent., (© 2023. The Author(s).)

Background: Socioeconomic deprivation drives poor functional outcomes after intracerebral hemorrhage (ICH). Stroke severity and background cerebral small vessel disease (CSVD) burden have each been linked to socioeconomic status and independently contribute to worse outcomes after ICH, providing distinct, plausible pathways for the effects of deprivation. We investigate whether admission stroke severity or cerebral small vessel disease (CSVD) mediates the effect of socioeconomic deprivation on 90-day functional outcomes., Methods: Electronic medical record data, including demographics, treatments, comorbidities, and physiological data, were analyzed. CSVD burden was graded from 0 to 4, with severe CSVD categorized as ≥3. High deprivation was assessed for patients in the top 30% of state-level area deprivation index scores. Severe disability or death was defined as a 90-day modified Rankin Scale score of 4-6. Stroke severity (NIH stroke scale (NIHSS)) was classified as: none (0), minor (1-4), moderate (5-15), moderate-severe (16-20), and severe (21+). Univariate and multivariate associations with severe disability or death were determined, with mediation evaluated through structural equation modelling., Results: A total of 677 patients were included (46.8% female; 43.9% White, 27.0% Black, 20.7% Hispanic, 6.1% Asian, 2.4% Other). In univariable modelling, high deprivation (odds ratio: 1.54; 95% confidence interval: [1.06-2.23]; p = 0.024), severe CSVD (2.14 [1.42-3.21]; p < 0.001), moderate (8.03 [2.76-17.15]; p < 0.001), moderate-severe (32.79 [11.52-93.29]; p < 0.001), and severe stroke (104.19 [37.66-288.12]; p < 0.001) were associated with severe disability or death. In multivariable modelling, severe CSVD (3.42 [1.75-6.69]; p < 0.001) and moderate (5.84 [2.27-15.01], p  < 0.001), moderate-severe (27.59 [7.34-103.69], p  < 0.001), and severe stroke (36.41 [9.90-133.85]; p < 0.001) independently increased odds of severe disability or death; high deprivation did not. Stroke severity mediated 94.1% of deprivation's effect on severe disability or death ( p  = 0.005), while CSVD accounted for 4.9% ( p  = 0.524)., Conclusion: CSVD contributed to poor functional outcome independent of socioeconomic deprivation, while stroke severity mediated the effects of deprivation. Improving awareness and trust among disadvantaged communities may reduce admission stroke severity and improve outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Potter, Tannous, Pan, Bako, Johnson, Baig, Kelly, McCane, Garg, Gadhia, Misra, Volpi, Britz, Chiu and Vahidy.)

In an emergency room (ER) setting, stroke triage or screening is a common challenge. A quick CT is usually done instead of MRI due to MRI's slow throughput and high cost. Clinical tests are commonly referred to during the process, but the misdiagnosis rate remains high. We propose a novel multimodal deep learning framework, DeepStroke, to achieve computer-aided stroke presence assessment by recognizing patterns of minor facial muscles incoordination and speech inability for patients with suspicion of stroke in an acute setting. Our proposed DeepStroke takes one-minute facial video data and audio data readily available during stroke triage for local facial paralysis detection and global speech disorder analysis. Transfer learning was adopted to reduce face-attribute biases and improve generalizability. We leverage a multi-modal lateral fusion to combine the low- and high-level features and provide mutual regularization for joint training. Novel adversarial training is introduced to obtain identity-free and stroke-discriminative features. Experiments on our video-audio dataset with actual ER patients show that DeepStroke outperforms state-of-the-art models and achieves better performance than both a triage team and ER doctors, attaining a 10.94% higher sensitivity and maintaining 7.37% higher accuracy than traditional stroke triage when specificity is aligned. Meanwhile, each assessment can be completed in less than six minutes, demonstrating the framework's great potential for clinical translation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

An intelligent-augmented lifelike avatar mobile app (iLAMA) that integrates computer vision and sensor readings to automate and streamline the NIH Stroke Scale (NIHSS) physical examination is presented. The user interface design is optimized for elderly patients while the app showcases an animated lifelike 3D model of a friendly physician who walks the user through the exam. The standardized NIHSS examination included in iLAMA consists of five core tasks. The first two tasks involve rolling the eyes to the left and then to the right, and then smiling as wide as the user can. The app determines facial landmarks and analyzes the palsy of the face. The next task is to extend the arm and hold the phone at the shoulder level, and the smart phone gyroscope is used to detect acceleration to determine possible weakness in the arm. Next, the app tracks the location of the hand keypoints and determines possible ataxia based on the precision and accuracy of the locations of the touches. Finally, the app determines the user's forward acceleration in walking and possible imbalances using the accelerometer. The app then sends analyzed results of these tasks to the neurologist or stroke specialist for review and decisions.Clinical Relevance- The physical examination of a stroke patient is a time consuming and repetitive process, and there is a lack of infrastructure and resource to monitor patient in post-stroke recovery after they leave the hospital for home or rehabilitation facilities. iLAMA app aims to automate a subset of the NIHSS physical examinations in measuring motor function recovery and also allows individual patients to track their performance over time. It will be an essential component in monitoring rehabilitation recovery and therapy effectiveness after hospitalization and can easily scaled to lo help millions of patients at a fraction of the cost.

Background: Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard management by emergency medical services (EMS). Whether and how much MSUs alter outcomes has not been extensively studied., Methods: In an observational, prospective, multicenter, alternating-week trial, we assessed outcomes from MSU or EMS management within 4.5 hours after onset of acute stroke symptoms. The primary outcome was the score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes according to a patient value system, derived from scores on the modified Rankin scale of 0 to 6, with higher scores indicating more disability). The main analysis involved dichotomized scores on the utility-weighted modified Rankin scale (≥0.91 or <0.91, approximating scores on the modified Rankin scale of ≤1 or >1) at 90 days in patients eligible for t-PA. Analyses were also performed in all enrolled patients., Results: We enrolled 1515 patients, of whom 1047 were eligible to receive t-PA; 617 received care by MSU and 430 by EMS. The median time from onset of stroke to administration of t-PA was 72 minutes in the MSU group and 108 minutes in the EMS group. Of patients eligible for t-PA, 97.1% in the MSU group received t-PA, as compared with 79.5% in the EMS group. The mean score on the utility-weighted modified Rankin scale at 90 days in patients eligible for t-PA was 0.72 in the MSU group and 0.66 in the EMS group (adjusted odds ratio for a score of ≥0.91, 2.43; 95% confidence interval [CI], 1.75 to 3.36; P<0.001). Among the patients eligible for t-PA, 55.0% in the MSU group and 44.4% in the EMS group had a score of 0 or 1 on the modified Rankin scale at 90 days. Among all enrolled patients, the mean score on the utility-weighted modified Rankin scale at discharge was 0.57 in the MSU group and 0.51 in the EMS group (adjusted odds ratio for a score of ≥0.91, 1.82; 95% CI, 1.39 to 2.37; P<0.001). Secondary clinical outcomes generally favored MSUs. Mortality at 90 days was 8.9% in the MSU group and 11.9% in the EMS group., Conclusions: In patients with acute stroke who were eligible for t-PA, utility-weighted disability outcomes at 90 days were better with MSUs than with EMS. (Funded by the Patient-Centered Outcomes Research Institute; BEST-MSU ClinicalTrials.gov number, NCT02190500.)., (Copyright © 2021 Massachusetts Medical Society.)

More than one third of ischemic strokes have an unidentifiable cause. Patent foramen ovale (PFO) plays a controversial role in this subset of patients. The evidence for and against the hypothesis of paradoxical embolism is reviewed and we discuss the optimal management of a PFO under different circumstances., (© 2016 Wiley Periodicals, Inc.)

Study Design: Prospective cohort study., Objective: To understand whether patients actually perceive increased limitations as compared with their preoperative state due to stiffness after lumbar arthrodesis., Summary of Background Data: Lumbar arthrodesis by intention eliminates spinal motion in an attempt to decrease pain, deformity, and instability. Independent of pain, loss of mobility can impact ability to perform certain activities of daily living. The lumbar stiffness disability index (LSDI) is a validated measure of the effect of lumbar stiffness on functional activities. To date, no prospective evaluations of stiffness impacts on patient function after lumbar arthrodesis have been reported., Methods: The LSDI, 36-Item Short Form Health Survey, and Oswestry Disability Index were administered preoperatively and at 2-year minimum follow-up to 62 adult patients undergoing lumbar fusion for degenerative disease or spinal deformity. Patients also completed a satisfaction questionnaire at 2 years. Patients were separated according to the number of lumbar arthrodesis levels. Pre- and postoperative LSDI, 36-Item Short Form Health Survey physical composite score, and Oswestry Disability Index scores were compared using paired t tests., Results: Significant improvements in Oswestry Disability Index were observed across all arthrodesis levels, and significant improvements in physical composite score were observed at level 1 and at 5 or more levels. Patients undergoing 1-level arthrodesis demonstrated statistically significant decreases in LSDI scores, indicating less impact from stiffness than at baseline. Patients with 3 or 4 levels and 5 or more levels of arthrodesis showed increases in LSDI scores, although none reached significance with the numbers available. Forty-six percent of patients reported that low back stiffness created significant limitations in activities of daily living, although 97% indicated that they would undergo the same procedure again and 91% reported that any increase in stiffness was an acceptable trade-off for their functional improvements from lumbar arthrodesis., Conclusion: Patients undergoing elective lumbar arthrodesis reported relatively limited functional deficit due to stiffness at 2-year follow-up. Paradoxically, patients undergoing 1-level arthrodesis actually reported significantly less limitation due to stiffness postoperatively. Although the effects of stiffness did trend toward greater impacts among patients undergoing longer fusions, 91% of patients were satisfied with trade-offs of function and pain relief in exchange for perceived increases in lumbar stiffness.

Herpes zoster ophthalmicus (HZO) is a common viral infectious disorder affecting the ophthalmic division of the trigeminal nerve. A small subset of HZO patients present with the ophthalmic symptoms, but without an accompanied rash, a condition described as Herpes zoster sine herpete. Although HZO is well known to be associated with other central nervous system abnormalities, encephalitis and cerebral infarction are atypical and uncommon. We report an unusual case of presumed unilateral Herpes zoster ophthalmicus sine herpete that presented with trigeminal pain and uveitis and then progressed to encephalitis and bilateral cerebral infarctions despite treatment with acyclovir and corticosteroids. The diagnosis of HZV was confirmed by polymerase chain reaction testing on the cerebrospinal fluid., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A 60-year-old man presented with diplopia and neurocognitive deficits, which progressed rapidly over several months. Magnetic resonance imaging of the head revealed bilateral signal abnormalities and diffusion-weighted imaging restriction in bilateral basal ganglia, thalami, mesial temporal regions, and periaqueductal gray matter. Cerebrospinal fluid analysis was positive for 14-3-3 and tau proteins. The patient developed progressive neurocognitive decline followed by sleep disturbance and myoclonic jerking consistent with probable Creutzfeldt-Jakob disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We present the first case of a woman with no significant medical history who developed dissections of bilateral carotid and bilateral vertebral arteries, as well as a retinal artery occlusion, after a roller coaster ride. A 35-year-old woman developed right-sided neck pain followed by a frontal headache immediately after a roller coaster ride. Five days after the incident, she developed complete loss of vision in her right eye for two hours. Subsequently, the vision improved but remained significantly decreased. On presentation, her visual acuity was 20/200 in the right and 20/20 in the left eye. Her fundus exam revealed retinal edema in the superotemporal retinal artery distribution without any visible emboli. Her neurological exam was otherwise normal. The cerebral angiogram showed bilateral internal carotid and vertebral artery dissections. The patient remained stable with conservative therapy without further worsening of vision or any new neurological deficits. Outcomes for cervicocephalic arterial dissection are usually favorable, but early diagnosis is critical for initiation of appropriate treatment of possible complications. Physicians must have a high index of suspicion for arterial dissection when patients note any headache, neck pain or vertigo triggered by violent motion after leisure activities such as roller coaster rides.

Moyamoya vasculopathy is a progressive, occlusive vasculopathy leading to ischemic and hemorrhagic strokes. No treatments are established to treat acute ischemic stroke with moyamoya vasculopathy. A 3-year-old girl with moyamoya syndrome developed acute left hemiplegia. Emergent angiography showed near-occlusion of the supraclinoid segment of the right internal carotid artery. Balloon angioplasty was performed within 6 hours of symptom onset, with significant improvement in the child's neurological symptoms. This is the youngest case of intracranial balloon angioplasty, and this article discusses the paucity of data regarding angioplasty and other forms of endovascular intervention in pediatric cerebrovascular disease and moyamoya vasculopathy. Further study is needed to determine the safety and efficacy of endovascular intervention in these diseases.