Symptomatic carotid webs require aggressive intervention.

OBJECTIVE: Carotid web (CaWeb) is a rare form of fibromuscular dysplasia that can produce embolic stroke. Misdiagnosis of symptomatic CaWeb as "cryptogenic stroke" or "embolic stroke of unknown source" is common and can lead to recurrent, catastrophic neurologic events. Reports of CaWeb in the literature are scarce, and their natural history is poorly understood. Appropriate management remains controversial. METHODS: CaWeb was defined as a single, shelf-like, linear projection in the posterolateral carotid bulb causing a filling defect on computed tomography angiography (CTA) or cerebral angiography. Cases of symptomatic CaWeb at a single institution with a high-volume stroke center were identified through collaborative evaluation by vascular neurologists and vascular surgeons. RESULTS: Fifty-two patients with symptomatic CaWeb were identified during a 6-year period (2016-2022). Average age was 49 years (range, 29-73 years), 35 of 52 (67%) were African American, and 18 of 52 (35%) were African American women under age 50. Patients initially presented with stroke (47/52; 90%) or transient ischemic attack (5/52; 10%). Stenosis was <50% in 49 of 52 patients (94%) based on NASCET criteria, and 0 of 52 (0%) CaWebs were identified with carotid duplex. Definitive diagnosis was made by CTA examined in multiple planes or cerebral angiography examined in a lateral projection to adequately assess the posterolateral carotid bulb, where 52 of 52 (100%) of CaWebs were seen. Early in our institutional experience, 10 of 52 patients (19%) with symptomatic CaWeb were managed initially with dual antiplatelet and statin therapy or systemic anticoagulation; all suffered ipsilateral recurrent stroke at an average interval of 43 months (range, 1-89 months), and five were left with permanent deficits. Definitive treatment included carotid endarterectomy in 27 of 50 (56%) or carotid stenting in 23 of 50 (46%). Two strokes were irrecoverable, and intervention was deferred. Web-associated thrombus was observed in 20 of 50 (40%) on angiography or grossly upon carotid exploration. Average interval from initial stroke to intervention was 39 days. After an average follow-up of 38 months, there was no reported postintervention stroke or mortality. CONCLUSIONS: To our knowledge, this is the largest single-institution analysis of symptomatic CaWeb yet reported. Our series demonstrates that carotid duplex is inadequate for diagnosis, and that medical management is unacceptable for symptomatic CaWeb. Recurrent stroke occurred in all patients managed early in our experience with medical therapy alone. We have since adopted an aggressive interventional approach in cases of symptomatic CaWeb, with no postoperative stroke reported over an average follow-up of 38 months. In younger patients presenting with cryptogenic stroke, especially African American women, detailed review of lateral cerebral angiography or multi-planar, fine-cut CTA images is required to accurately rule out or diagnose CaWeb and avoid recurrent neurologic events.

Detection of marine oil-like features in Sentinel-1 SAR images by supplementary use of deep learning and empirical methods: Performance assessment for the Great Barrier Reef marine park.

Continuous monitoring of oil discharges in coastal and open ocean waters using Earth Observation (EO) has undeniably contributed to diminishing their occurrence wherever a detection system was in place, such as in Europe (EMSA's CleanSeaNet) or in the United States (NOAA's OR&R). This study describes the development and testing of a semi-automated oil slick detection system tailored to the Great Barrier Reef (GBR) marine park solely based on EO data as no such service was routinely available in Australia until recently. In this study, a large, curated, historical global dataset of SAR imagery acquired by Sentinel-1 SAR, now publicly available, is used to assess classification techniques, namely an empirical approach and a deep learning model, to discriminate between oil-like features and look-alikes in the scenes acquired over the marine park. An evaluation of this detection system on 10 Sentinel-1 SAR images of the GBR using two performance metrics - the detection accuracy and the false-positive rate (FPR) - shows that the classifiers perform best when combined (accuracy >98 %; FPR 0.01) rather than when used separately. This study demonstrates the benefit of sequentially combining classifiers to improve the detection and monitoring of unreported oil discharge events in SAR imagery. The workflow has also been tested outside the GBR, demonstrating its robustness when applied to other regions such as Australia's Northwest Shelf, Southeast Asia and the Pacific.

GATM and GAMT synthesize creatine locally throughout the mammalian body and within oligodendrocytes of the brain.

The enzymes glycine amidinotransferase, mitochondrial (GATM also known as AGAT) and guanidinoacetate N-methyltransferase (GAMT) function together to synthesize creatine from arginine, glycine, and S-Adenosyl methionine. Deficiency in either enzyme or the creatine transporter, CT1, results in a devastating neurological disorder, Cerebral Creatine Deficiency Syndrome (CCDS). To better understand the pathophysiology of CCDS, we mapped the distribution of GATM and GAMT at single cell resolution, leveraging RNA sequencing analysis combined with in vivo immunofluorescence (IF). Using the mouse as a model system, we find that GATM and GAMT are coexpressed in several tissues with distinct and overlapping cellular sources, implicating local synthesis as an important mechanism of creatine metabolism in numerous organs. Extending previous findings at the RNA level, our analysis demonstrates that oligodendrocytes express the highest level of Gatm and Gamt of any cell type in the body. We confirm this finding in the mouse brain by IF, where GATM localizes to the mitochondria of oligodendrocytes, whereas both oligodendrocytes and cerebral cortical neurons express GAMT. Interestingly, the latter is devoid of GATM. Single nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) analysis of 4 brain regions highlights a similar primacy of oligodendrocytes in the expression of GATM and GAMT in the human central nervous system. Importantly, an active putative regulatory element within intron 2 of human GATM is detected in oligodendrocytes but not neurons.

Dorsal Hand Rejuvenation: A Systematic Review of the Literature.

BACKGROUND: Dorsal hand appearance undergoes changes with aging. Grading systems have been designed to provide numerical scores to dorsal hand appearance. Various modalities have been utilized to improve the aesthetic appearance and rejuvenate the dorsal hand. METHODS: The MEDLINE database was searched for articles investigating dorsal hand rejuvenation. Studies were grouped by method including fat grafting, injectable filler, laser/light-based treatments and miscellaneous treatments. Treatment protocols and outcomes were compiled along with patient information and complications. RESULTS: Forty-six articles were identified for inclusion. This included 9 studies of fat grafting procedures, 20 studies of injectable filler, 10 studies of laser/light-based treatments and 7 miscellaneous. Most studies showed overall good results with high patient satisfaction. Satisfaction rates were lower in laser/light-based treatments compared with the other modalities. The average patient age for included studies ranged from 41.5 to 69. Across all studies, 96.8% of patients were female and 3.2% male. CONCLUSIONS: Procedures for dorsal hand rejuvenation in the literature include procedures to address volume atrophy and superficial wrinkling. These procedures are overall safe with most studies reporting no complications or only mild adverse events. With high satisfaction rates and anecdotal reports of increasing patient interest, these procedures represent a developing area in aesthetic surgery likely to continue increasing in popularity. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Diffusion Tensor Imaging and Tractography Utilized in the Resection of a Midbrain Cavernous Malformation.

Background: Diffusion tensor imaging (DTI) is a magnetic resonance-based imaging technique that can provide important information about the underlying structure and integrity of the white matter in the brain. Tractography, a DTI postprocessing technique, can provide a detailed model of individual white matter fiber tracts. Knowledge of these tracts may be beneficial in the surgical planning and execution for neurosurgical patients. Case Report: We review the basic principles behind DTI and present an illustrative case in which DTI was used to delineate the relationship of eloquent white matter tracts to a cavernous malformation in a patient undergoing resection. Conclusion: The use of DTI during preoperative planning allows the neurosurgeon to understand if a lesion is disrupting, infiltrating, or altering the course of local white matter tracts. With the combined use of DTI and intraoperative neuronavigation, the neurosurgeon can better identify and avoid white matter tracts, not only in the local area of resection but also during approach to the lesion, thereby reducing the risk of damage to vital cortical pathways and subsequent functional impairment.

Development of a deformable lung phantom with 3D-printed flexible airways.

PURPOSE: Deformable lung phantoms have been proposed to investigate four-dimensional (4D) imaging and radiotherapy delivery techniques. However, most phantoms mimic only the lung and tumor without pulmonary airways. The purpose of this study was to develop a reproducible, deformable lung phantom with three-dimensional (3D)-printed airways. METHODS: The phantom consists of: (a) 3D-printed flexible airways, (b) flexible polyurethane foam infused with iodinated contrast agents, and (c) a motion platform. The airways were simulated using publicly available breath-hold computed tomography (CT) image datasets of a human lung through airway segmentation, computer-aided design modeling, and 3D printing with a rubber-like material. The lung was simulated by pouring liquid expanding foam into a mold with the 3D-printed airways attached. Iodinated contrast agents were infused into the lung phantom to emulate the density of the human lung. The lung/airways phantom was integrated into our previously developed motion platform, which allows for compression and decompression of the phantom in the superior-inferior direction. We quantified the reproducibility of the density (lung), motion/deformation (lung and airways), and position (airways) using breath-hold CT scans (with the phantom compressed and decompressed) repeated every two weeks over a 2-month period as well as 4D CT scans (with the phantom continuously compressed and decompressed) repeated twice over four weeks. The density reproducibility was quantified with a difference image (created by subtracting the rigidly registered baseline and the repeated images) in each of the compressed and decompressed states. Reproducibility of the motion/deformation was evaluated by comparing the baseline displacement vector fields (DVFs) derived from deformable image registration (DIR) between the compressed and decompressed phantom CT images with those of repeated scans and calculating the difference in the displacement vectors. Reproducibility of the airway position was quantified based on DIR between the baseline and repeated images. RESULTS: For the breath-hold CT scans, the mean difference in lung density between baseline and week 8 was -1.3 (standard deviation 33.5) Hounsfield unit (HU) in the compressed state and 0.4 (36.8) HU in the decompressed state, while large local differences were observed around the high-contrast structures (caused by small misalignments). By visual inspection, the DVFs (between the compressed and decompressed states) at baseline and last time point (week 8 for the breath-hold CT scans) demonstrated a similar pattern. The mean lengths of displacement vector differences between baseline and week 8 were 0.5 (0.4) mm for the lung and 0.3 (0.2) mm for the airways. The mean airway displacements between baseline and week 8 were 0.6 (0.5) mm in the compressed state and 0.6 (0.4) mm in the decompressed state. We also observed similar results for the 4D CT scans (week 0 vs week 4) as well as for the breath-hold CT scans at other time points (week 0 vs weeks 2, 4, and 6). CONCLUSIONS: We have developed a deformable lung phantom with 3D-printed airways based on a human lung CT image. Our findings indicate reproducible density, motion/deformation, and position. This phantom is based on widely available materials and technology, which represents advantages over other deformable phantoms.

Gadolinium Deposition in Neurology Clinical Practice.

Background: Magnetic resonance imaging (MRI) enhanced with gadolinium-based contrast agents (GBCAs) is an essential tool in the diagnosis and management of many neurologic diseases, including multiple sclerosis, brain tumors, and infections. The clinical utility of GBCAs is evidenced by their widespread use. GBCAs are produced in macrocyclic and linear forms. Since 2014, evidence has suggested that repeated administration of GBCAs can lead to gadolinium deposition in the brain. Methods: We review the literature on gadolinium deposition, including both animal and human studies, as well as the literature on GBCA-associated health outcomes. Additionally, we summarize and discuss the updated medical society recommendations and perspectives on GBCA use in clinical practice. Results: The first publication reporting gadolinium deposition in the human brain was published in 2014. Since that seminal report, multiple studies have demonstrated that exposure to linear GBCAs is associated with gadolinium deposition in the dentate nucleus and globus pallidus as seen on brain MRI. Macrocyclic GBCA exposure has not convincingly been associated with gadolinium deposition evident on brain MRI. Conclusion: Clear evidence demonstrates that GBCAs lead to gadolinium deposition in the brain in a dose-dependent manner; however, only linear GBCAs have been associated with gadolinium deposition visualized on MRI. To date, no evidence links gadolinium deposition with any adverse health outcome. Updated medical society guidelines emphasize the importance of an individualized risk-benefit analysis with each administration of GBCAs.

Survey of Current Management Practices for Carotid Webs.

Background: Carotid webs are thick, fibrous intimal bands that appear as intraluminal shelf-like defects at the carotid bifurcation on vascular imaging. These lesions are a potential underrecognized cause of cryptogenic ischemic stroke. Although the recognition of carotid webs has increased, no evidence-based treatment guidelines are available. We surveyed subspecialists across multiple neurologic disciplines to assess the state of current clinical practice. Methods: An 8-question multiple-choice style survey of neurologists and radiologists assessed familiarity with this disease entity, preferred imaging modalities, and management strategies for asymptomatic and symptomatic (producing stroke) carotid webs. Responses were collected through SurveyMonkey software via anonymous responses to a posted survey link on the Society of Neurointerventional Surgery website in addition to invitation emails sent to colleagues in corresponding fields. Results: Of the 74 total respondents, 64% identified as neurointerventionalists. Respondents identified computed tomography angiography as the most commonly used imaging modality to place carotid webs in the differential diagnosis (57% of respondents' preference), while conventional digital subtraction angiogram was the preferred modality to confirm a web (54% of respondents' preference). Respondents preferred single and dual antiplatelet therapy to manage asymptomatic and acute stroke-producing carotid webs, while invasive treatment was most commonly sought for webs producing recurrent strokes. Conclusion: Familiarity with carotid webs varied across subspecialties. We found some consensus among respondents on the imaging modality preferred to identify webs, on asymptomatic carotid web management, and on recurrently symptomatic (multiple strokes) carotid web management. Less consistency was seen regarding preferences for confirmatory imaging and management of acutely symptomatic (initial stroke) carotid webs.

Comparison of Polypropylene and Bioabsorbable Mesh for Abdominal Wall Reinforcement following Microsurgical Breast Reconstruction.

BACKGROUND: Abdominal wall morbidity following microvascular breast reconstruction continues to be an area of interest due to both functional and aesthetic concerns. Donor-site closure technique has been shown to affect bulge and hernia rates and ranges from primary closure to various uses of mesh. Few studies to date have compared types of mesh. The present study compares BARD polypropylene to bioabsorbable GORE Bio-A (polyglycolic acid/trimethylene carbonate) mesh used as a fascial underlay with primary fascial closure. METHODS: A retrospective review of all consecutive deep inferior epigastric artery-based microvascular breast reconstructions, including perforator and muscle-sparing flaps, performed between September 2014 and February 2017 was performed. All patients underwent primary fascial closure with mesh underlay. Risk factors for the formation of an abdominal bulge or hernia were identified by multivariate logistic regression. RESULTS: Eighty-seven patients, with 123 abdominal donor sites, were included. Heavy-weight polypropylene mesh was used for 58 donor sites, while polyglycolic acid/trimethylene carbonate mesh was used in 65 donor sites. The overall incidence of bulge or hernia was 11.4%. The bioabsorbable cohort experienced significantly more bulges/hernias than the polypropylene mesh cohort (20% vs. 1.7% by donor site). Time to diagnosis of bulge was longer for the bioabsorbable group (219 ± 107 vs. 69 days). Flap type and perforator row were not associated with bulge/hernia. The polyglycolic acid/trimethylene carbonate mesh was associated with a 13.3-fold risk of bulge/hernia (p = 0.016). CONCLUSION: Polyglycolic acid/trimethylene carbonate mesh is not appropriate for anterior rectus fascia reinforcement following abdominal tissue transfer.

Interleukin-4 activated macrophages mediate immunity to filarial helminth infection by sustaining CCR3-dependent eosinophilia.

Eosinophils are effectors in immunity to tissue helminths but also induce allergic immunopathology. Mechanisms of eosinophilia in non-mucosal tissues during infection remain unresolved. Here we identify a pivotal function of tissue macrophages (Mϕ) in eosinophil anti-helminth immunity using a BALB/c mouse intra-peritoneal Brugia malayi filarial infection model. Eosinophilia, via C-C motif chemokine receptor (CCR)3, was necessary for immunity as CCR3 and eosinophil impairments rendered mice susceptible to chronic filarial infection. Post-infection, peritoneal Mϕ populations proliferated and became alternatively-activated (AAMϕ). Filarial AAMϕ development required adaptive immunity and interleukin-4 receptor-alpha. Depletion of Mϕ prior to infection suppressed eosinophilia and facilitated worm survival. Add back of filarial AAMϕ in Mϕ-depleted mice recapitulated a vigorous eosinophilia. Transfer of filarial AAMϕ into Severe-Combined Immune Deficient mice mediated immunological resistance in an eosinophil-dependent manner. Exogenous IL-4 delivery recapitulated tissue AAMϕ expansions, sustained eosinophilia and mediated immunological resistance in Mϕ-intact SCID mice. Co-culturing Brugia with filarial AAMϕ and/or filarial-recruited eosinophils confirmed eosinophils as the larvicidal cell type. Our data demonstrates that IL-4/IL-4Rα activated AAMϕ orchestrate eosinophil immunity to filarial tissue helminth infection.

Differentiation of idiopathic spinal cord herniation from dorsal arachnoid webs on MRI and CT myelography.

OBJECTIVE Dorsal arachnoid webs (DAWs) and spinal cord herniation (SCH) are uncommon abnormalities affecting the thoracic spinal cord that can result in syringomyelia and significant neurological morbidity if left untreated. Differentiating these 2 entities on the basis of clinical presentation and radiological findings remains challenging but is of vital importance in planning a surgical approach. The authors examined the differences between DAWs and idiopathic SCH on MRI and CT myelography to improve diagnostic confidence prior to surgery. METHODS Review of the picture archiving and communication system (PACS) database between 2005 and 2015 identified 6 patients with DAW and 5 with SCH. Clinical data including demographic information, presenting symptoms and neurological signs, and surgical reports were collected from the electronic medical records. Ten of the 11 patients underwent MRI. CT myelography was performed in 3 patients with DAW and in 1 patient with SCH. Imaging studies were analyzed by 2 board-certified neuroradiologists for the following features: 1) location of the deformity; 2) presence or absence of cord signal abnormality or syringomyelia; 3) visible arachnoid web; 4) presence of a dural defect; 5) nature of dorsal cord indentation (abrupt "scalpel sign" vs "C"-shaped); 6) focal ventral cord kink; 7) presence of the nuclear trail sign (endplate irregularity, sclerosis, and/or disc-space calcification that could suggest a migratory path of a herniated disc); and 8) visualization of a complete plane of CSF ventral to the deformity. RESULTS The scalpel sign was positive in all patients with DAW. The dorsal indentation was C-shaped in 5 of 6 patients with SCH. The ventral subarachnoid space was preserved in all patients with DAW and interrupted in cases of SCH. In no patient was a web or a dural defect identified. CONCLUSIONS DAW and SCH can be reliably distinguished on imaging by scrutinizing the nature of the dorsal indentation and the integrity of the ventral subarachnoid space at the level of the cord deformity.

Neurologic and Head and Neck Manifestations of Sickle Cell Disease.

Sickle cell disease is a common, inherited disordered characterized by chronic hemolytic anemia with repetitive episodes of vasoocclusion resulting from deformed red blood cells. This article reviews the most significant neurologic and head and neck manifestations of this disease.

Venous Thrombosis: Causes and Imaging Appearance.

Cerebral venous sinus thrombosis is an elusive diagnosis with profound potential neurologic consequences. Although there are numerous reported predisposing conditions, by far the most common is a prothrombotic hypercoagulable state. Recent advances in MRI and computed tomography have improved diagnostic accuracy for this increasingly recognized disorder. Familiarity with imaging techniques and potential pitfalls is essential for accurate diagnosis and management of these patients.

Comparative miRNA-Based Fingerprinting Reveals Biological Differences in Human Olfactory Mucosa- and Bone-Marrow-Derived Mesenchymal Stromal Cells.

Previously we reported that nestin-positive human mesenchymal stromal cells (MSCs) derived from the olfactory mucosa (OM) enhanced CNS myelination in vitro to a greater extent than bone-marrow-derived MSCs (BM-MSCs). miRNA-based fingerprinting revealed the two MSCs were 64% homologous, with 26 miRNAs differentially expressed. We focused on miR-146a-5p and miR-140-5p due to their reported role in the regulation of chemokine production and myelination. The lower expression of miR-140-5p in OM-MSCs correlated with higher secretion of CXCL12 compared with BM-MSCs. Addition of CXCL12 and its pharmacological inhibitors to neural co-cultures supported these data. Studies on related miR-146a-5p targets demonstrated that OM-MSCs had lower levels of Toll-like receptors and secreted less pro-inflammatory cytokines, IL-6, IL-8, and CCL2. OM-MSCs polarized microglia to an anti-inflammatory phenotype, illustrating potential differences in their inflammatory response. Nestin-positive OM-MSCs could therefore offer a cell transplantation alternative for CNS repair, should these biological behaviors be translated in vivo.

Functional Neuroimaging: Fundamental Principles and Clinical Applications.

Functional imaging modalities, such as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), are rapidly changing the scope and practice of neuroradiology. While these modalities have long been used in research, they are increasingly being used in clinical practice to enable reliable identification of eloquent cortex and white matter tracts in order to guide treatment planning and to serve as a diagnostic supplement when traditional imaging fails. An understanding of the scientific principles underlying fMRI and DTI is necessary in current radiological practice. fMRI relies on a compensatory hemodynamic response seen in cortical activation and the intrinsic discrepant magnetic properties of deoxy- and oxyhemoglobin. Neuronal activity can be indirectly visualized based on a hemodynamic response, termed neurovascular coupling. fMRI demonstrates utility in identifying areas of cortical activation (i.e., task-based activation) and in discerning areas of neuronal connectivity when used during the resting state, termed resting state fMRI. While fMRI is limited to visualization of gray matter, DTI permits visualization of white matter tracts through diffusion restriction along different axes. We will discuss the physical, statistical and physiological principles underlying these functional imaging modalities and explore new promising clinical applications.

Potential of glyburide to reduce intracerebral edema in brain metastases.

Metastatic disease to the brain results in significant morbidity because of edema in the central nervous system. Current anti-edema therapies are either expensive or result in unwanted long-term side effects. Sulfonylurea receptor 1 (Sur1) is a transmembrane protein that, when activated in the central nervous system, allows for unregulated sodium influx into cells, a process that has been linked to cytotoxic edema formation in ischemic stroke, subarachnoid hemorrhage, spinal cord injury, traumatic brain injury, and, most recently, brain metastases. In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema.