Predictors of occlusion, long-term outcomes, and safety in a cohort of 674 aneurysms treated with the Pipeline embolization device.

OBJECTIVE: By providing a more physiological approach to the treatment of intracranial aneurysms, the Pipeline embolization device (PED) has revolutionized the endovascular treatment of aneurysms. Although there are many flow diverters on the market, the authors report their experience with the PED, the first flow diverter to be approved by the Food and Drug Administration. They aimed to assess the efficacy and safety of PED flow diversion for the treatment of a wide range of aneurysms, as well as to look at factors affecting occlusion. METHODS: This is a retrospective study of a prospectively maintained database of patients treated with the PED between January 2011 and December 2019. Charts were reviewed for patient, aneurysm, and procedure characteristics. The primary outcomes of interest were complication rates, occlusion outcomes (O'Kelly-Marotta grading scale), and functional outcomes (modified Rankin Scale [mRS]). Secondary outcomes included predictors of incomplete occlusion at 6 and 24 months of follow-up. RESULTS: The study cohort included 581 patients with 674 aneurysms. Most aneurysms (90.5%) were in the anterior circulation and had a saccular morphology (85.6%). Additionally, 638 aneurysms (94.7%) were unruptured, whereas 36 (5.3%) were acutely ruptured. The largest mean aneurysm diameter was 8.3 ± 6.1 mm. Complications occurred at a rate of 5.5% (n = 32). The complete occlusion rate was 89.3% at 24 months' follow-up, and 94.8% of patients had a favorable neurological outcome (mRS score 0-2) at the last follow-up. On multivariate analysis, predictors of incomplete aneurysm occlusion at 6 months were hypertension (OR 1.7, p = 0.03), previous aneurysm treatment (OR 2.4, p = 0.001), and increasing aneurysm neck diameter (OR 1.2, p = 0.02), whereas a saccular morphology was protective (OR 0.5, p = 0.05). Predictors of incomplete occlusion at 24 months were increasing aneurysm neck diameter (OR 1.2, p = 0.01) and previous aneurysm treatment (OR 2.3, p = 0.01). CONCLUSIONS: The study findings are corroborated by those of previous studies and trials. The complete occlusion rate was 89.3% at 24 months' follow-up, with 94.8% of patients having favorable functional outcomes (mRS score 0-2). Aneurysm treatment before PED deployment and an increasing aneurysm neck diameter increase the risk of incomplete occlusion at 6 and 24 months.

Brain-wide neuronal circuit connectome of human glioblastoma.

Glioblastoma (GBM), a universally fatal brain cancer, infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression 1-6 . Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic 7-9 . The extent of integration of GBM cells into brain-wide neuronal circuitry is not well understood. Here we applied a rabies virus-mediated retrograde monosynaptic tracing approach 10-12 to systematically investigate circuit integration of human GBM organoids transplanted into adult mice. We found that GBM cells from multiple patients rapidly integrated into brain-wide neuronal circuits and exhibited diverse local and long-range connectivity. Beyond glutamatergic inputs, we identified a variety of neuromodulatory inputs across the brain, including cholinergic inputs from the basal forebrain. Acute acetylcholine stimulation induced sustained calcium oscillations and long-lasting transcriptional reprogramming of GBM cells into a more invasive state via the metabotropic CHRM3 receptor. CHRM3 downregulation suppressed GBM cell invasion, proliferation, and survival in vitro and in vivo. Together, these results reveal the capacity of human GBM cells to rapidly and robustly integrate into anatomically and molecularly diverse neuronal circuitry in the adult brain and support a model wherein rapid synapse formation onto GBM cells and transient activation of upstream neurons may lead to a long-lasting increase in fitness to promote tumor infiltration and progression.

A Comparison of Outcomes Between Transfemoral Versus Transradial Access for Carotid Stenting.

BACKGROUND: The transradial (TR) approach has emerged as an alternative to the transfemoral (TF) approach in carotid artery stenting (CAS) because of its perceived benefits in access site complications and overall patient experience. OBJECTIVE: To assess outcomes of TF vs TR approach for CAS. METHODS: This is a retrospective single-center review of patients receiving CAS through the TR or TF route between 2017 and 2022. All patients with symptomatic and asymptomatic carotid disease who underwent attempted CAS were included in our study. RESULTS: A total of 342 patients were included in this study: 232 underwent CAS through TF approach vs 110 through the TR route. On univariate analysis, the rate of overall complications was more than double for the TF vs TR cohort; however, this did not achieve statistical significance (6.5% vs 2.7%, odds ratio [OR] = 0.59 P = .36). The rate of cross-over from TR to TF was significantly higher on univariate analysis (14.6 % vs 2.6%, OR = 4.77, P = .005) and on inverse probability treatment weighting analysis (OR = 6.11, P < .001). The rate of in-stent stenosis (TR: 3.6% vs TF: 2.2%, OR = 1.71, P = .43) and strokes at follow-up (TF: 2.2% vs TR: 1.8%, OR = 0.84, P = .84) was not significantly different. Finally, median length of stay was comparable between both cohorts. CONCLUSION: The TR approach is safe, feasible, and provides similar rates of complications and high rates of successful stent deployment compared with the TF route. Neurointerventionalists adopting the radial first approach should carefully assess the preprocedural computed tomography angiography to identify patients amenable to TR approach for carotid stenting.

Comparison of Flow-Redirection Endoluminal Device and Pipeline Embolization Device in the Treatment of Intracerebral Aneurysms.

BACKGROUND: The use of flow diverters for treating intracranial aneurysms has been widely used in the past decade; however, data comparing pipeline embolization device (PED; Medtronic Inc) and flow-redirection endoluminal device (FRED; MicroVention) in the treatment of intracranial aneurysms remain scarce. OBJECTIVE: To compare the outcomes of PED and FRED in the treatment of intracranial aneurysms. METHODS: This is a single-center retrospective review of aneurysms treated with PED and FRED devices. Patients treated with PED or FRED were included. Cases requiring multiple or adjunctive devices were excluded. Primary outcome was complete aneurysm occlusion at 6 months. Secondary outcomes included good functional outcome, need for retreatment, and any complication. RESULTS: The study cohort comprised 150 patients, including 35 aneurysms treated with FRED and 115 treated with PED. Aneurysm characteristics including location and size were comparable between the 2 cohorts. 6-month complete occlusion rate was significantly higher in the PED cohort (74.7% vs 51.5%; P = .017) but lost significance after inverse probability weights. Patients in the PED cohort were associated with higher rates of periprocedural complications (3.5% vs 0%; P = .573), and the rate of in-stent stenosis was approximately double in the FRED cohort (15.2% vs 6.9%; P = .172). CONCLUSION: Compared with PED, FRED offers modest 6-month occlusion rates, which may be due to aneurysmal and baseline patient characteristics differences between both cohorts. Although not significant, FRED was associated with a higher complication rate mostly because of in-stent stenosis. Additional studies with longer follow-up durations should be conducted to further evaluate FRED thrombogenicity.

Transradial versus transfemoral access routes for diagnostic cerebral angiography: a large single-center comparative cost-analysis study.

OBJECTIVE: Recently, the transradial (TR) approach has become a common alternative because of its safety profile and increased patient satisfaction compared with the transfemoral (TF) route. Both routes are associated with their respective associated costs, and differences typically emerge on the basis of patient anatomy, operator expertise, and occurrence of complications. The authors' objective was to compare the overall costs of diagnostic cerebral angiography via both routes and to shed light on the individual equipment costs of each route. METHODS: This retrospective single-center study of 926 elective diagnostic angiograms was performed between December 2019 and March 2022. RESULTS: The study comprised of 314 and 612 angiograms performed through the TF and TR routes, respectively. A significantly greater proportion of female patients were included in the TF cohort (79.3% vs 67.8%, p < 0.001), and most other demographic characteristics and baseline modified Rankin Scale scores were comparable between cohorts. The overall cost of patients utilizing the TR route was comparable to that of the TF route (mean ± SD $12,591.80 ± $19,128.00 vs $12,789.50 ± 18,424.00, p = 0.88). However, the median cost of catheters was significantly higher in TR group ($55.20 vs $12.40, p = 0.03), while the median costs of closure devices ($87.00 vs $20.20 p < 0.001) and sheaths ($44.60 ± 11.3 vs $41.10 ± 3.10, p < 0.001) were significantly higher in the TF group. CONCLUSIONS: Overall, the authors' study showed that the TR approach can be a less expensive option for patients undergoing diagnostic cerebral angiography, especially if complications occur. Future studies may corroborate these findings and potentially lead to the adoption of TR as a low-cost, efficient, gold-standard technique for cerebral angiography.

The Effect of COVID-19 Vaccines on Stroke Outcomes: A Single-Center Study.

BACKGROUND: One of the defining narratives of the COVID-19 pandemic has been the acceptance and distribution of vaccine. To compare the outcomes of COVID-19 positive vaccinated and unvaccinated stroke patients. METHODS: This is a single-center retrospective study of COVID-19-vaccinated and unvaccinated stroke patients between April 2020 and March 2022. All patients presenting with stroke regardless of treatment modalities were included. National Institutes of Health Stroke Scale was used to assess stroke severity. The primary outcome was functional capacity of the patients at discharge. RESULTS: The study cohort comprised 203 COVID-19 positive stroke patients divided into 139 unvaccinated and 64 fully vaccinated patients. At discharge, the modified Rankin scale score was significantly lower in the vaccinated cohort (3[1-4] vs. 4[2-5], odds ratio = 0.508, P = 0.011). At 3 months of follow-up, the median modified Rankin scale score was comparable between both cohorts. CONCLUSIONS: Although vaccination did not show any significant difference in stroke patient outcomes on follow-up, vaccines were associated with lower rates of morbidity and mortality at discharge among stroke patients during the pandemic.

History-dependent dopamine release increases cAMP levels in most basal amygdala glutamatergic neurons to control learning.

Dopaminergic inputs to basal amygdala (BA) instruct learning of motivational salience. This learning depends on intracellular plasticity signals such as cyclic adenosine monophosphate (cAMP), which is regulated by activation of dopamine receptors. We examine the dynamics of dopamine release and downstream signaling during multiple salient events occurring within tens of seconds. We perform real-time tracking and manipulation of cAMP in BA neurons in vitro and in vivo. Optogenetically evoked release of dopamine drives proportional increases in cAMP in almost all BA glutamatergic neurons, suggesting widespread actions of dopamine across neurons preferring positive or negative valence. This cAMP response decreases across trials with short intertrial intervals owing to depression of dopamine release. No such depression is evident when photostimulating cAMP production directly. cAMP and protein kinase A responses to repeated appetitive or aversive stimuli also exhibit pronounced depression. Thus, history-dependent dynamics of dopamine and cAMP may regulate learning of temporally clustered, salient stimuli.

Region-specific distribution of Olig2-expressing astrocytes in adult mouse brain and spinal cord.

Olig2 is an important transcription factor essential for the specification and differentiation of oligodendrocytes as well as astrocytes and neurons during developmental stages. However, Olig2 distribution pattern and its relationship among different types of glial cells in the adult central nervous system (CNS) are not well characterized. Here, we systematically examined Olig2 expression pattern in combination with major markers of neurons and glial cells throughout the brain and spinal cord in the adult mice. As expected, Olig2 is universally expressed in oligodendrocytes and oligodendrocyte precursor cells (OPCs), but not in neurons or microglia. Interestingly, we discover a subpopulation of Olig2+ astrocytes that are highly enriched in some specific regions including the olfactory bulb, thalamus, midbrain, medulla, and spinal cord in the adult mice. Moreover, OPCs have high expression level of Olig2, whereas oligodendrocytes and astrocytes have similar level of Olig2 expression. Our results suggest that a distinct population of Olig2+ astrocytes are highly concentrated in discrete regions in the adult CNS. Investigating the functional significance of these Olig2+ astrocytes in both resting state and pathological state of the brain and spinal cord may broaden our understanding on astrocytic heterogeneity and functions.

Transparent arrays of bilayer-nanomesh microelectrodes for simultaneous electrophysiology and two-photon imaging in the brain.

Transparent microelectrode arrays have emerged as increasingly important tools for neuroscience by allowing simultaneous coupling of big and time-resolved electrophysiology data with optically measured, spatially and type resolved single neuron activity. Scaling down transparent electrodes to the length scale of a single neuron is challenging since conventional transparent conductors are limited by their capacitive electrode/electrolyte interface. In this study, we establish transparent microelectrode arrays with high performance, great biocompatibility, and comprehensive in vivo validations from a recently developed, bilayer-nanomesh material composite, where a metal layer and a low-impedance faradaic interfacial layer are stacked reliably together in a same transparent nanomesh pattern. Specifically, flexible arrays from 32 bilayer-nanomesh microelectrodes demonstrated near-unity yield with high uniformity, excellent biocompatibility, and great compatibility with state-of-the-art wireless recording and real-time artifact rejection system. The electrodes are highly scalable, with 130 kilohms at 1 kHz at 20 µm in diameter, comparable to the performance of microelectrodes in nontransparent Michigan arrays. The highly transparent, bilayer-nanomesh microelectrode arrays allowed in vivo two-photon imaging of single neurons in layer 2/3 of the visual cortex of awake mice, along with high-fidelity, simultaneous electrical recordings of visual-evoked activity, both in the multi-unit activity band and at lower frequencies by measuring the visual-evoked potential in the time domain. Together, these advances reveal the great potential of transparent arrays from bilayer-nanomesh microelectrodes for a broad range of utility in neuroscience and medical practices.