Construction status and prospects of the Hyper-Kamiokande project

The Hyper-Kamiokande project is a 258-kton Water Cherenkov together with a 1.3-MW high-intensity neutrino beam from the Japan Proton Accelerator Research Complex (J-PARC). The inner detector with 186-kton fiducial volume is viewed by 20-inch photomultiplier tubes (PMTs) and multi-PMT modules, and thereby provides state-of-the-art of Cherenkov ring reconstruction with thresholds in the range of few MeVs. The project is expected to lead to precision neutrino oscillation studies, especially neutrino CP violation, nucleon decay searches, and low energy neutrino astronomy. In 2020, the project was officially approved and construction of the far detector was started at Kamioka. In 2021, the excavation of the access tunnel and initial mass production of the newly developed 20-inch PMTs was also started. In this paper, we present a basic overview of the project and the latest updates on the construction status of the project, which is expected to commence operation in 2027

Prospects for neutrino astrophysics with Hyper-Kamiokande

Hyper-Kamiokande is a multi-purpose next generation neutrino experiment. The detector is a two-layered cylindrical shape ultra-pure water tank, with its height of 64 m and diameter of 71 m. The inner detector will be surrounded by tens of thousands of twenty-inch photosensors and multi-PMT modules to detect water Cherenkov radiation due to the charged particles and provide our fiducial volume of 188 kt. This detection technique is established by Kamiokande and Super-Kamiokande. As the successor of these experiments, Hyper-K will be located deep underground, 600 m below Mt. Tochibora at Kamioka in Japan to reduce cosmic-ray backgrounds. Besides our physics program with accelerator neutrino, atmospheric neutrino and proton decay, neutrino astrophysics is an important research topic for Hyper-K. With its fruitful physics research programs, Hyper-K will play a critical role in the next neutrino physics frontier. It will also provide important information via astrophysical neutrino measurements, i.e., solar neutrino, supernova burst neutrinos and supernova relic neutrino. Here, we will discuss the physics potential of Hyper-K neutrino astrophysics

Flow-diverter reconstruction of an intracranial internal carotid artery dissection during thrombectomy for acute ischaemic stroke

Intracranial carotid artery dissections are challenging, as there are no specific guidelines for their treatment, and most research suggests solutions for treating those involving extracranial vessels. We describe a patient with an acute ischaemic stroke within the territory of the right internal carotid artery, who was found to have intracranial carotid artery dissection during the thrombectomy procedure. The dissected lumen was successfully reconstructed via deployment of a Derivo flow-diverter stent. A balloon-assisted 'jacking' manoeuvre, in which a balloon is partially inflated at the beginning of the dissection to serve as leverage, was used to overcome the challenge of navigating the microcatheter tip through the stenosis proximal to the dissection. This case demonstrates the feasibly and safety of stenting with a flow diverter in a patient with internal carotid artery dissection; however, further studies are needed to confirm this finding

Cerebrovascular disease burden in late-onset non-lesional focal epilepsy

Purpose: Late-onset non-lesional focal epilepsy, defined as new-onset seizures in patients older than 60 years, is diagnosed increasingly more often in relation to aging of the population. It has been attributed mainly to occult cerebral small vessel disease (SVD), although high levels of evidence to support this notion are lacking. This study aimed to evaluate the burden of leukoaraiosis, a marker of cerebral SVD, and hippocampal atrophy in patients with late-onset epilepsy (LOE). Methods: Brain magnetic resonance imaging (MRI) studies were retrospectively analyzed by two blinded radiologists. The Fazekas and Scheltens scales were used to assess the degree of leukoaraiosis and hippocampal atrophy in 33 patients with non-lesional LOE, 41 patients with clinical signs of SVD (eg, recent history of transient ischemic attack [TIA] or lacunar stroke), and 26 healthy controls, all >60 years of age. Results: Mean age in epilepsy patients was 70.9 (\ub16.6) years; 57.6% were men. The history of vascular risk factors was similar in all groups. Median (interquartile range) Fazekas score was 1 (0\u20131) in the epilepsy group, 1 (0\u20132) in TIA/lacunar stroke patients, and 0 (0\u20131) in the healthy group. Degree of leukoaraiosis was milder in epilepsy patients compared to the TIA/lacunar stroke group (p = 0.004), and similar to that of healthy controls (p = 0.593). Hippocampal atrophy was significantly greater in patients with epilepsy (p < 0.005). Conclusion: These findings suggest that the etiology of LOE is not exclusively related to cerebrovascular disease. Hippocampal atrophy may contribute to the origin of the seizures

L-dopa modulation of brain connectivity in Parkinson's disease patients: A pilot EEG-fmri study

Studies of functional neurosurgery and electroencephalography in Parkinson's disease have demonstrated abnormally synchronous activity between basal ganglia and motor cortex. Functional neuroimaging studies investigated brain dysfunction during motor task or resting state and primarily have shown altered patterns of activation and connectivity for motor areas. L-dopa administration relatively normalized these functional alterations. The aim of this pilot study was to examine the effects of L-dopa administration on functional connectivity in early-stage PD, as revealed by simultaneous recording of functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG) data. Six patients with diagnosis of probable PD underwent EEG-fMRI acquisitions (1.5 T MR scanner and 64-channel cap) before and immediately after the intake of L-dopa. Regions of interest in the primary motor and sensorimotor regions were used for resting state fMRI analysis. From the EEG data, weighted partial directed coherence was computed in the inverse space after the removal of gradient and cardioballistic artifacts. fMRI results showed that the intake of L-dopa increased functional connectivity within the sensorimotor network, and between motor areas and both attention and default mode networks. EEG connectivity among regions of the motor network did not change significantly, while regions of the default mode network showed a strong tendency to increase their outflow toward the rest of the brain. This pilot study provided a first insight into the potentiality of simultaneous EEG-fMRI acquisitions in PD patients, showing for both techniques the analogous direction of increased connectivity after L-dopa intake, mainly involving motor, dorsal attention and default mode networks

Encephalopathy in COVID-19 Presenting With Acute Aphasia Mimicking Stroke

Introduction: Neurological manifestations are emerging as relatively frequent complications of corona virus disease 2019 (COVID-19), including stroke and encephalopathy. Clinical characteristics of the latter are heterogeneous and not yet fully elucidated, while the pathogenesis appears related to neuroinflammation in a subset of patients. Case: A middle-aged man presented with acute language disturbance at the emergency department. Examination revealed expressive aphasia, mild ideomotor slowing, and severe hypocapnic hypoxemia. Multimodal CT assessment and electroencephalogram (EEG) did not reveal any abnormalities. COVID-19 was diagnosed based on chest CT findings and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR (RT-PCR) on nasopharyngeal swab. The following day, neurological symptoms progressed to agitated delirium and respiratory status worsened, requiring admission to the ICU and mechanical ventilation. Brain MRI and cerebrospinal fluid (CSF) studies were unremarkable. RT-PCR for SARS-CoV-2 on CSF was negative. He received supportive treatment and intravenous low-dose steroids. His neurological and respiratory status resolved completely within 2 weeks. Conclusions: We report a patient with reversible COVID-19-related encephalopathy presenting as acute aphasia, mimicking stroke or status epilepticus, eventually evolving into delirium. Although large-vessel stroke is frequently encountered in COVID-19, our case suggests that focal neurological deficits may occur as the earliest feature of encephalopathy. Neurological status reversibility and the absence of abnormalities on brain MRI are consistent with a functional rather than a structural neuronal network impairment

Procedural approaches and angiographic signs predicting first-pass recanalization in patients treated with mechanical thrombectomy for acute ischaemic stroke

Background: First-pass recanalization via mechanical thrombectomy (MT) has been associated with improved clinical outcome in patients with acute ischaemic stroke. The optimal approach to achieve first-pass effect (FPE) remains unclear. No study has evaluated angiographic features associated with the achievement of FPE. We aimed to determine the procedural approaches and angiographic signs that may predict FPE. Methods: We performed a prospective, multi-centre, observational study of FPE in patients with anterior circulation stroke treated with MT between February and June 2017. MTs were performed using different devices, deployment manoeuvres (standard versus \u2018Push and Fluff\u2019 technique), proximal balloon guide catheter (PBGC), distal aspiration catheter (DAC) or both. The angiographic clot protrusion sign (ACPS) was recorded. Completed FPE (cFPE) was defined as a modified thrombolysis in cerebral infarction score of 2c\u20133. Associations were sought between cFPE and procedural approaches and angiographic signs. Results: A total of 193 patients were included. cFPE was achieved in 74 (38.3%) patients. The use of the push and fluff technique (odds ratio (OR) 3.45, 95% confidence interval (CI): 1.28\u20139.29, p = 0.010), PBGC (OR 3.81, 95% CI: 1.41\u201310.22, p = 0.008) and ACPS (OR 4.71, 95% CI: 1.78\u201312.44, p = 0.002) were independently associated with cFPE. Concurrence of these three variables led to cFPE in 82 vs 35% of the remaining cases (p = 0.002). Conclusions: The concurrence of the PBGC, the push and fluff technique, and the ACPS was associated with the highest rates of cFPE. Appropriate selection of the thrombectomy device and deployment technique may lead to better procedural outcomes. ACPS could be used to assess clot integration strategies in future trials

Liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical long-term follow-up and pathogenic implications

We report the longest follow-up of clinical and biochemical features of two previously reported adult mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients treated with liver transplantation (LT), adding information on a third, recently transplanted, patient. All three patients overcame the early post-operative period and tolerated immunosuppressive therapy. Plasma nucleoside levels dramatically decreased, with evidence of clinical improvement of ambulation and neuropathy. Conversely, other features of MNGIE, as gastrointestinal dysmotility, low weight, ophthalmoparesis, and leukoencephalopathy were essentially unchanged. A similar picture characterized two patients treated with allogenic hematopoietic stem cell transplantation (AHSCT). In conclusion, LT promptly and stably normalizes nucleoside imbalance in MNGIE, stabilizing or improving some clinical parameters with marginal periprocedural mortality rate as compared to AHSCT. Nevertheless, restoring thymidine phosphorylase (TP) activity, achieved by both LT and AHSCT, does not allow a full clinical recovery, probably due to consolidated cellular damage and/or incomplete enzymatic tissue replacement

T2K ND280 Upgrade - Technical Design Report

In this document, we present the Technical Design Report of the Upgrade of the T2K Near Detector ND280. The goal of this upgrade is to improve the Near Detector performance to measure the neutrino interaction rate and to constrain the neutrino interaction cross-sections so that the uncertainty in the number of predicted events at Super-Kamiokande is reduced to about 4%. This will allow to improve the physics reach of the T2K-II project. This goal is achieved by modifying the upstream part of the detector, adding a new highly granular scintillator detector (Super-FGD), two new TPCs (High-Angle TPC) and six TOF planes. Details about the detector concepts, design and construction methods are presented, as well as a first look at the test-beam data taken in Summer 2018. An update of the physics studies is also presented