Polygenic routes lead to parallel altitudinal adaptation in Heliosperma pusillum (Caryophyllaceae).

Understanding how organisms adapt to the environment is a major goal of modern biology. Parallel evolution-the independent evolution of similar phenotypes in different populations-provides a powerful framework to investigate the evolutionary potential of populations, the constraints of evolution, its repeatability and therefore its predictability. Here, we quantified the degree of gene expression and functional parallelism across replicated ecotype formation in Heliosperma pusillum (Caryophyllaceae), and gained insights into the architecture of adaptive traits. Population structure analyses and demographic modelling support a previously formulated hypothesis of parallel polytopic divergence of montane and alpine ecotypes. We detect a large proportion of differentially expressed genes (DEGs) underlying divergence within each replicate ecotype pair, with a strikingly low number of shared DEGs across pairs. Functional enrichment of DEGs reveals that the traits affected by significant expression divergence are largely consistent across ecotype pairs, in strong contrast to the nonshared genetic basis. The remarkable redundancy of differential gene expression indicates a polygenic architecture for the diverged adaptive traits. We conclude that polygenic traits appear key to opening multiple routes for adaptation, widening the adaptive potential of organisms.

Recurrent allopolyploidizations diversify ecophysiological traits in marsh orchids (Dactylorhiza majalis s.l.).

Whole-genome duplication has shaped the evolution of angiosperms and other organisms, and is important for many crops. Structural reorganization of chromosomes and repatterning of gene expression are frequently observed in allopolyploids, with physiological and ecological consequences. Recurrent origins from different parental populations are widespread among polyploids, resulting in an array of lineages that provide excellent models to uncover mechanisms of adaptation to divergent environments in early phases of polyploid evolution. We integrate here transcriptomic and ecophysiological comparative studies to show that sibling allopolyploid marsh orchid species (Dactylorhiza, Orchidaceae) occur in different habitats (low nutrient fens vs. meadows with mesic soils) and are characterized by a complex suite of intertwined, pronounced ecophysiological differences between them. We uncover distinct features in leaf elemental chemistry, light-harvesting, photoprotection, nutrient transport and stomata activity of the two sibling allopolyploids, which appear to match their specific ecologies, in particular soil chemistry differences at their native sites. We argue that the phenotypic divergence between the sibling allopolyploids has a clear genetic basis, generating ecological barriers that maintain distinct, independent lineages, despite pervasive interspecific gene flow. This suggests that recurrent origins of polyploids bring about a long-term potential to trigger and maintain functional and ecological diversity in marsh orchids and other groups.

Testing the potential contribution of Wolbachia to speciation when cytoplasmic incompatibility becomes associated with host-related reproductive isolation.

Endosymbiont-induced cytoplasmic incompatibility (CI) may play an important role in arthropod speciation. However, whether CI consistently becomes associated or coupled with other host-related forms of reproductive isolation (RI) to impede the transfer of endosymbionts between hybridizing populations and further the divergence process remains an open question. Here, we show that varying degrees of pre- and postmating RI exist among allopatric populations of two interbreeding cherry-infesting tephritid fruit flies (Rhagoletis cingulata and R. indifferens) across North America. These flies display allochronic and sexual isolation among populations, as well as unidirectional reductions in egg hatch in hybrid crosses involving southwestern USA males. All populations are infected by a Wolbachia strain, wCin2, whereas a second strain, wCin3, only co-infects flies from the southwest USA and Mexico. Strain wCin3 is associated with a unique mitochondrial DNA haplotype and unidirectional postmating RI, implicating the strain as the cause of CI. When coupled with nonendosymbiont RI barriers, we estimate the strength of CI associated with wCin3 would not prevent the strain from introgressing from infected southwestern to uninfected populations elsewhere in the USA if populations were to come into secondary contact and hybridize. In contrast, cytoplasmic-nuclear coupling may impede the transfer of wCin3 if Mexican and USA populations were to come into contact. We discuss our results in the context of the general paucity of examples demonstrating stable Wolbachia hybrid zones and whether the spread of Wolbachia among taxa can be constrained in natural hybrid zones long enough for the endosymbiont to participate in speciation.

Comparative genome sequencing reveals insights into the dynamics of Wolbachia in native and invasive cherry fruit flies.

Wolbachia is a maternally inherited obligate endosymbiont that can induce a wide spectrum of effects in its host, ranging from mutualism to reproductive parasitism. At the genomic level, recombination within and between strains, transposable elements, and horizontal transfer of strains between host species make Wolbachia an evolutionarily dynamic bacterial system. The invasive cherry fruit fly Rhagoletis cingulata arrived in Europe from North America ~40 years ago, where it now co-occurs with the native cherry pest R. cerasi. This shared distribution has been proposed to have led to the horizontal transfer of different Wolbachia strains between the two species. To better understand transmission dynamics, we performed a comparative genome study of the strain wCin2 in its native United States and invasive European populations of R. cingulata with wCer2 in European R. cerasi. Previous multilocus sequence genotyping (MLST) of six genes implied that the source of wCer2 in R. cerasi was wCin2 from R. cingulata. However, we report genomic evidence discounting the recent horizontal transfer hypothesis for the origin of wCer2. Despite near identical sequences for the MLST markers, substantial sequence differences for other loci were found between wCer2 and wCin2, as well as structural rearrangements, and differences in prophage, repetitive element, gene content, and cytoplasmic incompatibility inducing genes. Our study highlights the need for whole-genome sequencing rather than relying on MLST markers for resolving Wolbachia strains and assessing their evolutionary dynamics.

The Use of Intracranial Vessel Wall Magnetic Resonance Imaging to Detect a Presumptive Syphilitic Brain Aneurysm.

ABSTRACT: Syphilitic intracranial aneurysm is a rare presentation of meningovascular syphilis in developed countries. In this case report, we discuss the utilization of the intracranial vessel wall magnetic resonance imaging in the management of a patient with a rare fusiform brain aneurysm, positive syphilis serologies, and inconclusive cerebrospinal fluid findings.

Adaptive sequence evolution is driven by biotic stress in a pair of orchid species (Dactylorhiza) with distinct ecological optima.

The orchid family is the largest in the angiosperms, but little is known about the molecular basis of the significant variation they exhibit. We investigate here the transcriptomic divergence between two European terrestrial orchids, Dactylorhiza incarnata and Dactylorhiza fuchsii, and integrate these results in the context of their distinct ecologies that we also document. Clear signals of lineage-specific adaptive evolution of protein-coding sequences are identified, notably targeting elements of biotic defence, including both physical and chemical adaptations in the context of divergent pools of pathogens and herbivores. In turn, a substantial regulatory divergence between the two species appears linked to adaptation/acclimation to abiotic conditions. Several of the pathways affected by differential expression are also targeted by deviating post-transcriptional regulation via sRNAs. Finally, D. incarnata appears to suffer from insufficient sRNA control over the activity of RNA-dependent DNA polymerase, resulting in increased activity of class I transposable elements and, over time, in larger genome size than that of D. fuchsii. The extensive molecular divergence between the two species suggests significant genomic and transcriptomic shock in their hybrids and offers insights into the difficulty of coexistence at the homoploid level. Altogether, biological response to selection, accumulated during the history of these orchids, appears governed by their microenvironmental context, in which biotic and abiotic pressures act synergistically to shape transcriptome structure, expression and regulation.

Global phosphoproteomic profiling reveals distinct signatures in B-cell non-Hodgkin lymphomas.

Deregulation of signaling pathways controlled by protein phosphorylation underlies the pathogenesis of hematological malignancies; however, the extent to which deregulated phosphorylation may be involved in B-cell non-Hodgkin lymphoma (B-NHL) pathogenesis is largely unknown. To identify phosphorylation events important in B-NHLs, we performed mass spectrometry-based, label-free, semiquantitative phosphoproteomic profiling of 11 cell lines derived from three B-NHL categories: Burkitt lymphoma, follicular lymphoma, and mantle-cell lymphoma. In all, 6579 unique phosphopeptides, corresponding to 1701 unique phosphorylated proteins, were identified and quantified. The data are available via ProteomeXchange with identifier PXD000658. Hierarchical clustering highlighted distinct phosphoproteomic signatures associated with each lymphoma subtype. Interestingly, germinal center-derived B-NHL cell lines were characterized by phosphorylation of proteins involved in the B-cell receptor signaling. Of these proteins, phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) was identified with the most phosphorylated tyrosine peptides in Burkitt lymphoma and follicular lymphoma. PAG1 knockdown resulted in perturbation of the tyrosine phosphosignature of B-cell receptor signaling components. Significantly, PAG1 knockdown increased cell proliferation and response to antigen stimulation of these germinal center-derived B-NHLs. These data provide a detailed annotation of phosphorylated proteins in human lymphoid cancer. Overall, our study revealed the utility of unbiased phosphoproteome interrogation in characterizing signaling networks that may provide insights into pathogenesis mechanisms in B-cell lymphomas.

Integrated phosphoproteomic and metabolomic profiling reveals NPM-ALK-mediated phosphorylation of PKM2 and metabolic reprogramming in anaplastic large cell lymphoma.

The mechanisms underlying the pathogenesis of the constitutively active tyrosine kinase nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) expressing anaplastic large cell lymphoma are not completely understood. Here we show using an integrated phosphoproteomic and metabolomic strategy that NPM-ALK induces a metabolic shift toward aerobic glycolysis, increased lactate production, and biomass production. The metabolic shift is mediated through the anaplastic lymphoma kinase (ALK) phosphorylation of the tumor-specific isoform of pyruvate kinase (PKM2) at Y105, resulting in decreased enzymatic activity. Small molecule activation of PKM2 or expression of Y105F PKM2 mutant leads to reversal of the metabolic switch with increased oxidative phosphorylation and reduced lactate production coincident with increased cell death, decreased colony formation, and reduced tumor growth in an in vivo xenograft model. This study provides comprehensive profiling of the phosphoproteomic and metabolomic consequences of NPM-ALK expression and reveals a novel role of ALK in the regulation of multiple components of cellular metabolism. Our studies show that PKM2 is a novel substrate of ALK and plays a critical role in mediating the metabolic shift toward biomass production and tumorigenesis.

Fusion peptides from oncogenic chimeric proteins as putative specific biomarkers of cancer.

Chromosomal translocations encoding chimeric fusion proteins constitute one of the most common mechanisms underlying oncogenic transformation in human cancer. Fusion peptides resulting from such oncogenic chimeric fusions, though unique to specific cancer subtypes, are unexplored as cancer biomarkers. Here we show, using an approach termed fusion peptide multiple reaction monitoring mass spectrometry, the direct identification of different cancer-specific fusion peptides arising from protein chimeras that are generated from the juxtaposition of heterologous genes fused by recurrent chromosomal translocations. Using fusion peptide multiple reaction monitoring mass spectrometry in a clinically relevant scenario, we demonstrate the specific, sensitive, and unambiguous detection of a specific diagnostic fusion peptide in clinical samples of anaplastic large cell lymphoma, but not in a diverse array of benign lymph nodes or other forms of primary malignant lymphomas and cancer-derived cell lines. Our studies highlight the utility of fusion peptides as cancer biomarkers and carry broad implications for the use of protein biomarkers in cancer detection and monitoring.

TCR-dependent and -independent activation underlie liver-specific regulation of NKT cells.

The fate of invariant NKT (iNKT) cells following activation remains controversial and unclear. We systemically examined how iNKT cells are regulated following TCR-dependent and -independent activation with α-galactosylceramide (αGC) or IL-18 plus IL-12, respectively. Our studies reveal activation by αGC or IL-18 plus IL-12 induced transient depletion of iNKT cells exclusively in the liver that was independent of caspase 3-mediated apoptosis. The loss of iNKT cells was followed by repopulation and expansion of phenotypically distinct cells via different mechanisms. Liver iNKT cell expansion following αGC, but not IL-18 plus IL-12, treatment required an intact spleen and IFN-γ. Additionally, IL-18 plus IL-12 induced a more prolonged expansion of liver iNKT cells compared with αGC. iNKT cells that repopulate the liver following αGC had higher levels of suppressive receptors PD-1 and Lag3, whereas those that repopulate the liver following IL-18 plus IL-12 had increased levels of TCR and ICOS. In contrast to acute treatment that caused a transient loss of iNKT cells, chronic αGC or IL-18 plus IL-12 treatment caused long-term systemic loss requiring an intact thymus for repopulation of the liver. This report reveals a previously undefined role for the liver in the depletion of activated iNKT cells. Additionally, TCR-dependent and -independent activation differentially regulate iNKT cell distribution and phenotype. These results provide new insights for understanding how iNKT cells are systemically regulated following activation.

The need for a systematic approach to statin switching: an analysis of real-world experience.

BACKGROUND: In the advent of generic statins becoming increasingly available and with the recent addition of atorvastatin to the generic market, healthcare providers are often encouraged by payers to switch from a branded statin to an alternate, less costly agent. OBJECTIVE: The aim of this study was to determine the impact of a therapeutic switch on cholesterol goal attainment among patients with existing cardiovascular disease (CVD) or risk factors for CVD. STUDY DESIGN: A cross-sectional, multisite retrospective review of patient records evaluating low-density lipoprotein cholesterol (LDL-C) control before and after switching statins was conducted. METHODS: Participants were 18 to 89 years olds who were stable on statin therapy and had 1 or more risk factors for CVD. Patients meeting switch criteria (n = 833) were evaluated for changes in their statin therapy and LDL-C goal attainment. Drug/dose information, cholesterol values, and goal attainment in accordance with National Cholesterol Education Panel Third Adult Treatment Panel guidelines were determined before and after the switch. Dose potency was based on mean LDL-C reductions. RESULTS: Data were collected from 22 US sites. Risk factors for CVD were common, with 88.5% of patients identified as high risk. Overall, patients' mean LDL-C levels improved from 87.1 to 81.5 mg/dL, and goal attainment increased from 75.5% to 82.5% (P < .05). Switches to a comparable or higher statin/dose improved mean LDL-C and goal attainment (P < .05). However, in patients transitioned to a lower statin/dose equivalency (36.4%), mean LDL-C level increased from 79.8 to 85.6 mg/dL and goal attainment fell from 84.2% to 78.6% (P < .05). Logistic regression confirmed that LDL-C goal attainment was reduced by 53% in patients switched to a lower statin/dose (odds ratio, 0.47; 95% confidence interval, 0.30-0.76; P = .002) compared with patients switched to an equipotent dose. The use of adjunctive lipid-lowering therapies increased in patients switched to a lower statin/dose (P < .05). CONCLUSIONS: Cholesterol values and goal attainment can be negatively impacted when a systematic approach is not used and patients are switched to lower potency therapies.

The COVID-19 pandemic's impact on all-cause mortality disparities in Medicare: By race, income, chronic health, mental/behavioral health, disability.

BACKGROUND: The Medicare-enrolled population is heterogeneous across race, ethnicity, age, dual eligibility, and a breadth of chronic health, mental and behavioral health, and disability-related conditions, which may be differentially impacted by the COVID-19 pandemic. OBJECTIVE: To quantify changes in all-cause mortality prior-to and in the first year of the COVID-19 pandemic across Medicare's different sociodemographic and health-condition subpopulations. METHODS: This observational, population-based study used stratified bivariate regression to investigate Medicare fee-for-service subpopulation differences in pre-pandemic (i.e., 2019 versus 2016) and pandemic-related (2020 versus 2019) changes in all-cause mortality. RESULTS: All-cause mortality in the combined Medicare-Advantage (i.e., managed care) and fee-for-service beneficiary population improved by a relative 1% in the ten years that preceded the COVID-19 pandemic, but then escalated by a relative 15.9% in 2020, the pandemic's first year. However, a closer look at Medicare's fee-for-service subpopulations reveals critical differences. All-cause mortality had actually been worsening prior to the pandemic among most psychiatric and disability-related condition groups, all race and ethnicity groups except White Non-Hispanic, and Medicare-Medicaid dual-eligible (i.e., low-income) beneficiaries. Many of these groups then experienced all-cause mortality spikes in 2020 that were over twice that of the overall Medicare fee-for-service population. Of all 61 chronic health conditions studied, beneficiaries with schizophrenia were the most adversely affected, with all-cause mortality increasing 38.4% between 2019 and 2020. CONCLUSION: This analysis reveals subpopulation differences in all-cause mortality trends, both prior to and in year-one of the COVID-19 pandemic, indicating that the events of 2020 exacerbated preexisting health-related inequities.

A novel intrasaccular aneurysm device with high complete occlusion rate: initial results in a rabbit model.

BACKGROUND: Intrasaccular flow-disrupting devices are a safe and effective treatment strategy for intracranial aneurysms. We utilized high-frequency optical coherence tomography (HF-OCT) and digital subtraction angiography (DSA) to evaluate SEAL Arc, a new intrasaccular device, and compare the findings with the well-established Woven EndoBridge (WEB) device in an animal model of saccular aneurysms. METHODS: In a rabbit model, elastase-induced aneurysms were treated with SEAL Arc (n=11) devices. HF-OCT and DSA were performed after implant and repeated after 12 weeks. Device protrusion and malapposition were assessed at implant time and scored on a binary system. Aneurysm occlusion was assessed at 12 weeks with the WEB Occlusion Scale and dichotomized to complete (A and B) or incomplete (C and D) occlusion. The percentage of neointimal coverage after 12 weeks was quantified using HF-OCT. We compared these data to previously published historical controls treated with the gold-standard WEB device (n=24) in the same model. RESULTS: Aneurysm size and device placement were not significantly different between the two groups. Complete occlusion was demonstrated in 80% of the SEAL Arc devices, which compared favorably to the 21% of the aneurysms treated with WEB devices (P=0.002). Neointimal coverage across SEAL Arc devices was 86±15% compared with 49±27% for WEB (P=0.001). Protruding devices had significantly less neointimal coverage (P<0.001) as did incompletely occluded aneurysms (P<0.001). Histologically, all aneurysms treated with SEAL Arc devices were completely healed. CONCLUSION: Complete early aneurysm occlusion was frequently observed in the SEAL Arc treated aneurysms, with significant neointimal coverage after 12 weeks.

Treatment of a ruptured shallow trilobed cerebral aneurysm with the novel saccular endovascular aneurysm lattice (SEAL) device: A case report with one year follow-up.

Intrasaccular flow disruption is a viable alternative to other endovascular treatments for saccular or wide-necked bifurcation intracranial aneurysms; however, wide neck aneurysms with irregular shapes or shallow depth may not be amenable to treatment currently available intrasaccular devices. Here, we present the first ever case report of the novel Saccular Endovascular Aneurysm Lattice Embolization System (SEAL™). The versatile utility of the SEAL™ device is demonstrated in a patient with acute subarachnoid hemorrhage (SAH) from a ruptured, complex, left middle cerebral artery (MCA) trilobed shallow wide-necked bifurcation aneurysm. Deployment and implantation of the SEAL device were technically feasible, safe, and conformed well to the irregular shape of the complex, ruptured aneurysm. Immediate total aneurysm occlusion was observed after implantation. Importantly, 1-year angiographic follow-up demonstrated durable, complete occlusion with no safety concerns. The SEAL device is a promising new novel technology which has the potential to treat very shallow aneurysms with limited height and irregular, multilobulated aneurysms.

Cerebral Venous Sinus Thrombosis Associated With Coronavirus Disease 2019: Case Report and Review of the Literature.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with significant risk of acute thrombosis. We present a case report of a patient with cerebral venous sinus thrombosis (CVST) associated with COVID-19 and performed a literature review of CVST associated with COVID-19 cases. CASE REPORT: A 38-year-old woman was admitted with severe headache and acute altered mental status a week after confirmed diagnosis of COVID-19. Magnetic resonance imaging brain showed diffuse venous sinus thrombosis involving the superficial and deep veins, and diffuse edema of bilateral thalami, basal ganglia and hippocampi because of venous infarction. Her neurological exam improved with anticoagulation (AC) and was subsequently discharged home. We identified 43 patients presenting with CVST associated with COVID-19 infection. 56% were male with mean age of 51.8±18.2 years old. The mean time of CVST diagnosis was 15.6±23.7 days after onset of COVID-19 symptoms. Most patients (87%) had thrombosis of multiple dural sinuses and parenchymal changes (79%). Almost 40% had deep cerebral venous system thrombosis. Laboratory findings revealed elevated mean D-dimer level (7.14/mL±12.23 mg/L) and mean fibrinogen level (4.71±1.93 g/L). Less than half of patients had prior thrombotic risk factors. Seventeen patients (52%) had good outcomes (mRS <=2). The mortality rate was 39% (13 patients). CONCLUSION: CVST should be in the differential diagnosis when patients present with acute neurological symptoms in this COVID pandemic. The mortality rate of CVST associated with COVID-19 can be very high, therefore, early diagnosis and prompt treatment are crucial to the outcomes of these patients.

Limb-shaking transient ischemic attack masquerading as lumbar radiculopathy from pericallosal artery stenosis treated successfully with intracranial angioplasty and stenting.

The pericallosal artery is rarely associated with intracranial atherosclerotic disease and, until recently, was usually not amenable to endovascular therapy with balloon angioplasty and stenting. We present an elderly patient with postural left leg-shaking episodes secondary to pericallosal artery stenosis, which was treated initially with primary intracranial balloon angioplasty, and subsequently, angioplasty and stenting as a result of recurrent stenosis. Both procedures were preformed without complications, and the patient remained free of symptoms on 6-month follow-up. This case demonstrates unique clinical and neuroendovascular aspects; the isolated postural leg-shaking transient ischemic attacks, initially mistaken for radiculopathy and local joint etiology, were found later to be cerebrovascular ischemic in origin. Moreover, the correlation between the findings of computed tomography perfusion and angiography localized the lesion into the medial frontal lobe and pericallosal artery territory. In addition, the technical aspect provides insight into the current state of neuroendovascular techniques, addressing the difficulty of access into very small and distal intracranial arteries affected by stenosis.

Creation of a High-Yield AAV Vector Production Platform in Suspension Cells Using a Design-of-Experiment Approach.

Recombinant adeno-associated virus (rAAV) vectors are a leading gene delivery platform, but vector manufacturing remains a challenge. New methods are needed to increase rAAV yields and reduce costs. Past efforts to improve rAAV production have focused on optimizing a single variable at a time, but this approach does not account for the interactions of multiple factors that contribute to vector generation. Here, we utilized a design-of-experiment (DOE) methodology to optimize rAAV production in a HEK293T suspension cell system. We simultaneously varied the transgene, packaging, and helper plasmid ratios, the total DNA concentration, and the cell density to systematically evaluate the impact of each variable across 52 conditions. The results revealed a unique set of parameters with a lower concentration of transgene plasmid, a higher concentration of packaging plasmid, and a higher cell density than previously described protocols. Using this DOE-optimized protocol, we achieved unpurified yields approaching 3 × 1014 viral genomes (VGs)/L of cell culture. Additionally, we incorporated polyethylene glycol (PEG)-based virus precipitation, pH-mediated protein removal, and affinity chromatography to our downstream processing, enabling average purified yields of >1 × 1014 VGs/L for rAAV-EGFPs across 13 serotypes and capsid variants.

Management of intracranial pressure.

Although intracranial hypertension may arise from diverse pathology, several basic principles remain paramount to understanding its dynamics; however, the management of elevated intracranial pressure (ICP) may be very complex. Initial management of common ICP exacerbants is important, such as addressing venous outflow obstruction with upright midline head positioning and treating agitation and pain with sedation and analgesia. Surgical decompression of mass effect may rapidly improve ICP elevation, but the impact on outcome is unclear. Considerable effort has been put forth to understand the roles of multimodal intensive care monitoring, osmolar therapy, cerebral metabolic suppression, and temperature augmentation in the advanced management of elevated ICP. Establishing a protocol-driven approach to the management of ICP enables the rapid bedside assessment of multiple physiologic variables to implement appropriate treatments, which limit the risk of developing secondary brain injury.

Pediatric cerebral angiography: analysis of utilization and findings.

Pediatric neuroendovascular procedures are being performed with increasing frequency, for various indications. Reported here is the experience of interventionally trained neurologists performing pediatric cerebral diagnostic angiography between August 1, 2005, and April 30, 2008, at a single tertiary institution. Data regarding patient demographics, diagnostic indication and angiographic diagnosis, procedural complications, and procedural specifications were recorded to assess practice patterns and to track procedural morbidity. In all, 42 patients had 46 procedures during the study period. Mean age was 9.97 years (standard deviation S.D. = 5.39; range, 0.3-18 years); 22/42 were male (52%). Known or suspected vascular malformation was the diagnostic indication for 20 patients; of these, 12 had an arteriovenous malformation, 5 had venous abnormalities, and 3 exhibited no angiographic vascular malformations. In 13 total procedures there was no angiographic pathology. General anesthesia was used in 29/46 procedures (63%). A total of 190 cerebral arteries were individually selected, with a mean number of vessels catheterized of 4.1 (S.D. = 1.7) per procedure. No procedural thromboembolic complications, iatrogenic arterial dissection, or neurologic or vascular access site complications occurred. In conclusion, pediatric cerebral angiography seems to be generally safe, although there should be a strong diagnostic indication, given the inherent procedural risk.

Interventional acute ischemic stroke therapy with intracranial self-expanding stent.

BACKGROUND AND PURPOSE: Rapid and safe recanalization of occluded intracranial arteries in acute ischemic stroke (AIS) is challenging. Newly available self-expanding intracranial atherosclerotic stents (SEIS), which can be deployed rapidly and safely, make acute stenting an option for treating AIS. We present the feasibility of this technique. METHODS: A retrospective analysis evaluated procedural protocols and clinical response to treatment in patients with AIS treated with SEIS. Descriptive statistics are presented with initial and follow-up National Institutes of Health Stroke Scale and modified Rankin Score. RESULTS: Nine patients with AIS underwent acute SEIS placement. There was successful deployment of the Neuroform (n=4) and Wingspan (n=4/5) stents in the M1/M2 (n=5) and M3 (n=1) middle cerebral artery segments, intracranial internal carotid artery (one of 2), and intracranial vertebrobasilar junction (one). Mean time of SEIS deployment from AIS onset was 5.1 hours. Complete (Thrombolysis in Cerebral Ischemia/Thrombolysis in Myocardial Ischemia 3) and partial/complete (Thrombolysis in Cerebral Ischemia/Thrombolysis in Myocardial Ischemia 2 or 3) recanalization occurred in 67% and 89%, respectively. One intracranial hemorrhage (11%) and one acute in-stent thrombosis (successfully treated with abciximab and balloon angioplasty) occurred. Stroke-related mortality occurred in 3 of 9 (33%) patients and survivors had modified Rankin Score < or = 2. Follow-up angiography (mean, 8 months; range, 2 to 14 months) in 4 of 9 patients showed no stent restenosis. CONCLUSIONS: This preliminary experience with SEIS in refractory AIS demonstrated the technical feasibility and high rate of recanalization with acute stenting. Long-term safety and strategies to limit in-stent thrombosis and optimize periprocedural management are crucial before initiating future randomized efficacy studies with SEIS in AIS refractory to standard therapy.