Efficacy of Endovascular Treatment for Acute Cerebral Large-Vessel Occlusion: Analysis of Nationwide Prospective Registry

BackgroundThe aim of this nationwide, prospective registry of acute cerebral large-vessel occlusion was to assess the efficacy of endovascular treatment (EVT) on outcome in the “real-world” settings.MethodsMedical information of the patients was anonymized and registered prospectively through a Web site from 84 medical centers in Japan. Reperfusion of the affected arteries was evaluated by the Thrombolysis in Cerebral Infarction grade on cerebral angiography or by the modified Mori grade on magnetic resonance angiography. Clinical outcome was evaluated by modified Rankin Scale (mRS) at 90 days after onset. Symptomatic intracranial hemorrhage and procedure-related complications were also analyzed.ResultsAmong intravenous tissue plasminogen activator (IV t-PA)–failed patients, no significant difference in favorable outcome was seen with or without EVT overall (41.7% versus 36.8%, P = .55). However, EVT significantly increased favorable outcomes (mRS score 0-2) in patients with internal carotid artery (ICA)/middle cerebral artery M1/basilar artery (BA) occlusion (41.3% versus 20.5%, P = .019). In contrast, among t-PA–ineligible patients, EVT significantly increased favorable outcomes overall (29.1% versus 19.5%; odds ratio, 1.70; P = .007). Furthermore, favorable outcomes were more common in patients with ICA/M1/BA occlusion (29.0% versus 10.3%; odds ratio, 3.56; P < .0001). Multivariate analysis also confirmed the efficacy of IV t-PA, EVT, and their combination for favorable outcome.ConclusionsEVT significantly improved clinical outcomes in IV t-PA–failed and t-PA–ineligible patients with ICA/M1/BA occlusion. These findings support the introduction of EVT for acute proximal artery occlusion

追悼 藤枝憲二 先生

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Myelination and long diffusion times alter diffusion-tensor-imaging contrast in myelin-deficient shiverer mice

Diffusion tensor imaging (DTI) using variable diffusion times (t(diff)) was performed to investigate wild-type (wt) mice, myelin-deficient shiverer (shi) mutant mice and shi mice transplanted with wt neural precursor cells that differentiate and function as oligodendrocytes. At t(diff) = 30 ms, the diffusion anisotropy volume ratio (VR), diffusion perpendicular to the fibers (lambda( perpendicular)), and mean apparent diffusion coefficient () of the corpus callosum of shi mice were significantly higher than those of wt mice by 12 +/- 2%, 13 +/- 2%, and 10 +/- 1%, respectively; fractional anisotropy (FA) and relative anisotropy (RA) were lower by 10 +/- 1% and 11 +/- 3%, respectively. Diffusion parallel to the fibers (lambda(//)) was not statistically different between shi and wt mice. Normalized T(2)-weighted signal intensities showed obvious differences (27 +/- 4%) between wt and shi mice in the corpus callosum but surprisingly did not detect transplant-derived myelination. In contrast, diffusion anisotropy maps detected transplant-derived myelination in the corpus callosum and its spatial distribution was consistent with the donor-derived myelination determined by immunohistochemical staining. Anisotropy indices (except lambda(//)) in the corpus callosum showed strong t(diff) dependence (30-280 ms), and the differences in lambda( perpendicular) and VR between wt and shi mice became significantly larger at longer t(diff), indicative of improved DTI sensitivity at long t(diff). In contrast, anisotropy indices in the hippocampus showed very weak t(diff) dependence and were not significantly different between wt and shi mice across different t(diff). This study provides insights into the biological signal sources and measurement parameters influencing DTI contrast, which could lead to developing more sensitive techniques for detection of demyelinating diseases

Schematic diagramas showing an overview of mutation detection methods.

<p>(<b>A</b>) In patients with McCune-Albright syndrome, the proportion of mutation-carrying cells (colored red) is low in peripheral blood leukocytes (PBL). (<b>B</b>) In the present study, PCR amplification was conducted in the absence (<i>left panel</i>) or presence (<i>right panel</i>) of the peptide nucleic acid (PNA) probe. The PNA probe preferentially hybridizes to wildtype PCR fragments (colored black) and inhibits their amplification. This results in enrichment of mutant PCR fragments (colored red). We used chimeric PCR primers, containing both locus-specific and adapter sequences, to generate amplicons that are sequenced on the Illumina platform. (<b>C</b>) PCR without the PNA probe produces PCR amplicons, of which relative proportion between wildtype (colored black) and mutant (colored red) is similar to PBL (<i>left panel</i>). In contrast, PNA treatment enriches mutant amplicons (<i>right panel</i>). (<b>D</b>)<b>,</b> PCR amplicons were analyzed by both Sanger sequencing and next generation sequencing (‘NGS’). Due to low mutation abundance, mutations cannot be detected in amplicons generated without the PNA probe (<i>left panel</i>), while they can be detected in PNA-treated amplicons (<i>right panel,</i> an arrow indicates the mutation). In the MiSeq platform, clonal clusters, each derived from a single DNA molecule, are generated on a flow cell, and are sequenced base-by-base simultaneously and independently. The diagrams under the schematic flow cells show imaginative optically scanned data of the cycle corresponding to the mutated nucleotide. In a sample without PNA treatment, the mutant amplicons can be recognized on the flow cell (<i>left panel</i>). Mutant-enriched samples are also analyzable by NGS (<i>right panel</i>).</p

Separate oscillating cell groups in mouse suprachiasmatic nucleus couple photoperiodically to the onset and end of daily activity

The pattern of circadian behavioral rhythms is photoperiod-dependent, highlighted by the conservation of a phase relation between the behavioral rhythm and photoperiod. A model of two separate, but mutually coupled, circadian oscillators has been proposed to explain photoperiodic responses of behavioral rhythm in nocturnal rodents: an evening oscillator, which drives the activity onset and entrains to dusk, and a morning oscillator, which drives the end of activity and entrains to dawn. Continuous measurement of circadian rhythms in clock gene Per1 expression by a bioluminescence reporter enabled us to identify the separate oscillating cell groups in the mouse suprachiasmatic nucleus (SCN), which composed circadian oscillations of different phases and responded to photoperiods differentially. The circadian oscillation in the posterior SCN was phase-locked to the end of activity under three photoperiods examined. On the other hand, the oscillation in the anterior SCN was phase-locked to the onset of activity but showed a bimodal pattern under a long photoperiod [light–dark cycle (LD)18:6]. The bimodality in the anterior SCN reflected two circadian oscillatory cell groups of early and late phases. The anterior oscillation was unimodal under intermediate (LD12:12) and short (LD6:18) photoperiods, which was always phase-lagged behind the posterior oscillation when the late phase in LD18:6 was taken. The phase difference was largest in LD18:6 and smallest in LD6:18. These findings indicate that three oscillating cell groups in the SCN constitute regionally specific circadian oscillations, and at least two of them are involved in photoperiodic response of behavioral rhythm