Endovascular thrombectomy for treatment of isolated posterior cerebral artery occlusion: a real-world analysis of hospitalizations in the United States.

BACKGROUND: Despite renewed interest and recently demonstrated efficacy for endovascular thrombectomy (EVT) for treatment of acute ischemic stroke (AIS) of the posterior circulation, to date, no randomized clinical trials have been conducted to evaluate EVT for isolated occlusions of the posterior cerebral artery (IPCA). METHODS: Hospitalizations for adult patients with primary admission diagnoses of IPCA occlusion were identified in the National Inpatient Sample registry during the period of 2016-2020. The study exposure was treatment with EVT, and primary clinical endpoints included favorable functional outcome (defined as discharge disposition to home without services, previously shown to have high concordance with modified Rankin scale scores 0-2), in-hospital mortality, and any intracranial hemorrhage (ICH). Inverse probability of treatment weighting (IPTW) was performed to balance baseline clinical characteristics between those receiving EVT or medical management (MM). RESULTS: This analysis identified 34,880 IPCA occlusion hospitalizations, 730 (2.1%) of which documented treatment with EVT. Following IPTW adjustment, EVT was associated with favorable outcome in IPCA patients presenting with mild deficits (M-D) (NIHSS < 6) [adjusted odds ratio (aOR) 2.36, 95% confidence interval (CI) 2.27, 2.45; p < 0.001] and in those presenting with moderate-to-severe deficits (M-S-D) (NIHSS 6-42) (aOR 2.00, 95% CI 1.86, 2.15; p < 0.001). Mortality rates did not differ among those with M-S-D [EVT 4.8% vs. MM 4.7%, p = 0.742], while ICH rates were lower. CONCLUSION: Retrospective analysis of a large administrative registry in the Unites States demonstrates an association of EVT with favorable outcomes following IPCA occlusion, without concomitant risk of hemorrhagic transformation or mortality.

Treatment trends and clinical outcomes of endovascular embolization for unruptured intracranial aneurysms in the pediatric population.

BACKGROUND: Owing to the relative rarity of unruptured intracranial aneurysms (UIAs) in the pediatric population, evidence regarding treatment modalities and clinical outcomes remains limited. OBJECTIVE: To characterize the use and clinical outcomes of endovascular therapy (EVT) and microsurgical clipping (MSC) for pediatric UIAs over a two-decade interval using a large national registry. METHODS: Pediatric (<18 years of age) UIA hospitalizations were identified in the National Inpatient Sample from 2002 to 2019. Temporal use and clinical outcomes were compared for treatment with EVT and MSC. RESULTS: Among 734 UIAs identified, 64.9% (n=476) were treated with EVT. Use of EVT significantly increased during the study period from 54.3% (2002-2004) to 78.6% (2017-2019) (P=0.002 by Cochrane-Armitage test). In comparison with those treated with MSC, pediatric patients treated with EVT demonstrated higher rates of favorable outcomes (discharge to home without services) (96.0% vs 91.1%, P=0.006), shorter durations of hospital stay (4.6 vs 10.0 days, P<0.001), and lower rates of ischemic or hemorrhagic procedural-related complications (1% vs 4%, P=0.010). Conservative management also increased significantly over the study period (P<0.001 by Cochrane-Armitage test). CONCLUSION: A retrospective evaluation of nearly 20 years of population-level data from the United States demonstrates increasing use of EVT for the treatment of pediatric UIAs, with high rates of favorable outcomes and shorter hospital stays in comparison with those treated with microsurgery.

Mapping geographic disparities in treatment and clinical outcomes of high-grade aneurysmal subarachnoid hemorrhage in the United States.

BACKGROUND AND OBJECTIVE: Although high-grade (Hunt and Hess 4 and 5) aneurysmal subarachnoid hemorrhage (aSAH) typically portends a poor prognosis, early and aggressive treatment has previously been demonstrated to confer a significant survival advantage. This study aims to evaluate geographic, demographic, and socioeconomic determinants of high-grade aSAH treatment in the United States. METHODS: The National Inpatient Sample (NIS) was queried to identify adult high-grade aSAH hospitalizations during the period of 2015 to 2019 using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD) codes. The primary clinical endpoint of this analysis was aneurysm treatment by surgical or endovascular intervention (SEI), while the exposure of interest was geographic region by census division. Favorable functional outcome (assessed by the dichotomous NIS-SAH Outcome Measure, or NIS-SOM) and in-hospital mortality were evaluated as secondary endpoints in treated and conservatively managed groups. RESULTS: Among 99 460 aSAH patients identified, 36 795 (37.0%) were high-grade, and 9210 (25.0%) of these were treated by SEI. Following multivariable logistic regression analysis, determinants of treatment by SEI included female sex (adjusted OR (aOR) 1.42, 95% CI 1.35 to 1.51), transfer admission (aOR 1.18, 95% CI 1.12 to 1.25), private insurance (ref: government-sponsored insurance) (aOR 1.21, 95% CI 1.14 to 1.28), and government hospital ownership (ref: private ownership) (aOR 1.17, 95% CI 1.09 to 1.25), while increasing age (by decade) (aOR 0.93, 95% CI 0.91 to 0.95), increasing mortality risk (aOR 0.60, 95% CI 0.57 to 0.63), urban non-teaching hospital status (aOR 0.66, 95% CI 0.59 to 0.73), rural hospital location (aOR 0.13, 95% CI 0.7 to 0.25), small hospital bedsize (aOR 0.68, 95% CI 0.60 to 0.76), and geographic region (South Atlantic (aOR 0.72, 95% CI 0.63 to 0.83), East South Central (aOR 0.75, 95% CI 0.64 to 0.88), and Mountain (aOR 0.72, 95% CI 0.61 to 0.85)) were associated with a lower likelihood of treatment. High-grade aSAH patients treated by SEI experienced significantly greater rates of favorable functional outcomes (20.1% vs 17.3%; OR 1.20, 95% CI 1.13 to 1.28, P<0.001) and lower rates of mortality (25.8% vs 49.1%; OR 0.36, 95% CI 0.34 to 0.38, P<0.001) in comparison to those conservatively managed. CONCLUSION: A complex interplay of demographic, socioeconomic, and geographic factors influence treatment patterns of high-grade aSAH in the United States.

A Model to Study NMDA Receptors in Early Nervous System Development.

N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that play critical roles in neuronal development and nervous system function. Here, we developed a model to study NMDARs in early development in zebrafish, by generating CRISPR-mediated lesions in the NMDAR genes, grin1a and grin1b, which encode the obligatory GluN1 subunits. While receptors containing grin1a or grin1b show high Ca2+ permeability, like their mammalian counterpart, grin1a is expressed earlier and more broadly in development than grin1b Both grin1a-/- and grin1b-/- zebrafish are viable. Unlike in rodents, where the grin1 knockout is embryonic lethal, grin1 double-mutant fish (grin1a-/-; grin1b-/-), which lack all NMDAR-mediated synaptic transmission, survive until ∼10 d dpf (days post fertilization), providing a unique opportunity to explore NMDAR function during development and in generating behaviors. Many behavioral defects in the grin1 double-mutant larvae, including abnormal evoked responses to light and acoustic stimuli, prey-capture deficits, and a failure to habituate to acoustic stimuli, are replicated by short-term treatment with the NMDAR antagonist MK-801, suggesting that they arise from acute effects of compromised NMDAR-mediated transmission. Other defects, however, such as periods of hyperactivity and alterations in place preference, are not phenocopied by MK-801, suggesting a developmental origin. Together, we have developed a unique model to study NMDARs in the developing vertebrate nervous system.SIGNIFICANCE STATEMENT Rapid communication between cells in the nervous system depends on ion channels that are directly activated by chemical neurotransmitters. One such ligand-gated ion channel, the NMDAR, impacts nearly all forms of nervous system function. It has been challenging, however, to study the prolonged absence of NMDARs in vertebrates, and hence their role in nervous system development, due to experimental limitations. Here, we demonstrate that zebrafish lacking all NMDAR transmission are viable through early development and are capable of a wide range of stereotypic behaviors. As such, this zebrafish model provides a unique opportunity to study the role of NMDAR in the development of the early vertebrate nervous system.