当前期刊: "神经"类期刊
显示样式:        排序: 导出
我的关注
我的收藏
您暂时未登录!
登录
  • Neuroprotective effect of microglia against impairments of auditory steady-state response induced by anti-P IgG from SLE patients in naïve mice
    J. Neuroinflammation (IF 5.7) Pub Date : 2020-01-23
    Xuejiao Wang; Yingzhuo Li; Zijie Li; Jinhong Li; Jingyi Xu; Pingting Yang; Ling Qin

    Autoantibodies against ribosomal P proteins (anti-P antibodies) are strongly associated with the neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE). The present study was designed to assess whether anti-P antibodies can induce abnormal brain electrical activities in mice and investigate the potential cytopathological mechanism. Affinity-purified human anti-ribosomal P antibodies were injected intravenously into mice after blood–brain barrier (BBB) disruption. The auditory steady-state response (ASSR) was evaluated based on electroencephalography (EEG) signals in response to 40-Hz click-train stimuli, which were recorded from electrodes implanted in the skull of mice. Immunofluorescence staining was used to examine the morphology and density of neurons and glia in the hippocampus and cortex. The presence of apoptosis in the brain tissues was studied using the TUNEL assay. A PLX3397 diet was used to selectively eliminate microglia from the brains of mice. Circulating anti-P antibodies caused an enhancement of the ASSR and the activation of microglia through the disrupted BBB, while no obvious neural apoptosis was observed. In contrast, when microglia were depleted, anti-P antibodies induced a serious reduction in the ASSR and neural apoptosis. Our study indicates that anti-P antibodies can directly induce the dysfunction of auditory-evoked potentials in the brain and that microglia are involved in the protection of neural activity after the invasion of anti-P antibodies, which could have important implications for NPSLE.

    更新日期:2020-01-23
  • Correction to: C3aR signaling and gliosis in response to neurodevelopmental damage in the cerebellum
    J. Neuroinflammation (IF 5.7) Pub Date : 2020-01-23
    Kevin G. Young; Keqin Yan; David J. Picketts

    Following publication of the original article, the authors noticed missing labels in Fig. 1a

    更新日期:2020-01-23
  • Health comorbidities and cognitive abilities across the lifespan in Down syndrome
    J. Neurodev. Disord. (IF 3.59) Pub Date : 2020-01-23
    Carla M. Startin; Hana D’Souza; George Ball; Sarah Hamburg; Rosalyn Hithersay; Kate M. O. Hughes; Esha Massand; Annette Karmiloff-Smith; Michael S. C. Thomas; Andre Strydom

    Down syndrome (DS) is associated with variable intellectual disability and multiple health and psychiatric comorbidities. The impact of such comorbidities on cognitive outcomes is unknown. We aimed to describe patterns of physical health and psychiatric comorbidity prevalence, and receptive language ability, in DS across the lifespan, and determine relationships with cognitive outcomes. Detailed medical histories were collected and cognitive abilities measured using standardised tests for 602 individuals with DS from England and Wales (age range 3 months to 73 years). Differences in prevalence rates between age groups and between males and females were determined using chi-squared or Fisher’s exact tests. In adults, rates for psychiatric comorbidities were compared to expected population rates using standardised morbidity ratios (SMRs). Adapted ANCOVA functions were constructed to explore age and sex associations with receptive language ability across the lifespan, and regression analyses were performed to determine whether the presence of health comorbidities or physical phenotypes predicted cognitive abilities. Multiple comorbidities showed prevalence differences across the lifespan, though there were few sex differences. In adults, SMRs were increased in males and decreased in females with DS for schizophrenia, bipolar disorder, and anxiety. Further, SMRs were increased in both males and females with DS for dementia, autism, ADHD, and depression, with differences more pronounced in females for dementia and autism, and in males for depression. Across the lifespan, receptive language abilities increasingly deviated from age-typical levels, and males scored poorer than females. Only autism and epilepsy were associated with poorer cognitive ability in those aged 16–35 years, with no relationships for physical health comorbidities, including congenital heart defects. Our results indicate the prevalence of multiple comorbidities varies across the lifespan in DS, and in adults, rates for psychiatric comorbidities show different patterns for males and females relative to expected population rates. Further, most health comorbidities are not associated with poorer cognitive outcomes in DS, apart from autism and epilepsy. It is essential for clinicians to consider such differences to provide appropriate care and treatment for those with DS and to provide prognostic information relating to cognitive outcomes in those with comorbidities.

    更新日期:2020-01-23
  • Risk factor analysis for progressive spinal deformity after resection of intracanal tumors─ a retrospective study of 272 cases
    BMC Neurol. (IF 2.233) Pub Date : 2020-01-23
    Pangbo Wang; Kang Ma; Tunan Chen; Xingsen Xue; Dada Ma; Shi Wang; Xin Chen; Hui Meng; Gaoyu Cui; Boyuan Gao; Jiangkai Lin; Hua Feng; Weihua Chu

    Progressive spinal deformity has become a well-recognized complication of intracanal tumors resection. However, the factors affecting post-operative spinal stability remain to be further research. Here, we described the current largest series of risk factors analysis for progressive spinal deformity following resection of intracanal tumors. We retrospectively analyzed the medical records of the patients with resection of intracanal tumors between January 2009 and December 2018. All patients who underwent resection of intracanal tumors performed regular postoperative follow-up were identified and included in the study. Clinical, radiological, surgical, histopathological, and follow-up data were collected. The incidence of postoperative progressive kyphosis or scoliosis was calculated. The statistical relationship between postoperative progressive spinal deformity and radiographic, clinical, and surgical variables was assessed by using univariate tests and multivariate logistic regression analysis. Two hundred seventy-two patients (mean age 42.56 ± 16.18 years) with median preoperative modified McCormick score of 3 met the inclusion criteria. Among them, 7(2.6%)patients were found to have spinal deformity preoperatively, and the extent of spinal deformity in these 7 patients deteriorated after surgery. 36 (13.2%) were new cases of postoperative progressive deformity. The mean duration of follow-up was 21.8 months (median 14 months, range 6–114 months). In subsequent multivariate logistic regression analysis, age ≤ 18 years (p = 0.027), vertebral levels of tumor involvement (p = 0.019) and preoperative spinal deformity(p = 0.008) was the independent risk factors (p < 0.05), increasing the odds of postoperative progressive spinal deformity by 3.94-, 0.69- and 27.11-fold, respectively. The incidence of postoperative progressive spinal deformity was 15.8%, mostly in these patients who had younger age (≤18 years), tumors involved in multiple segments and preoperative spinal deformity. The risk factors of postoperative progressive spinal deformity warrants serious reconsideration that when performing resection of spinal cord tumors in these patients with such risk factors, the surgeons should consider conducting follow-ups more closely, and when patients suffering from severe symptoms or gradually increased spinal deformity, surgical spinal fusion may be a more suitable choice to reduce the risk of reoperation and improve the prognosis of patients.

    更新日期:2020-01-23
  • Space: A Missing Piece of the Dynamic Puzzle
    Trends Cogn. Sci. (IF 16.173) Pub Date : 2020-01-23
    Armin Iraji; Robyn Miller; Tulay Adali; Vince D. Calhoun

    There has been growing interest in studying the temporal reconfiguration of brain functional connectivity to understand the role of dynamic interaction (e.g., integration and segregation) among neuronal populations in cognitive functions. However, it is crucial to differentiate between various dynamic properties because nearly all existing dynamic connectivity studies are presented as spatiotemporally dynamic, even though they fall into different categories. As a result, variation in the spatial patterns of functional structures are not well characterized. Here, we present the concepts of spatially, temporally, and spatiotemporally dynamics and use this terminology to categorize existing approaches. We review current spatially dynamic connectivity work, emphasizing that explicit incorporation of space into dynamic analyses can expand our understanding of brain function and disorder.

    更新日期:2020-01-23
  • Imaging Biomarkers of Alzheimer's Disease in Multiple Sclerosis
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-22
    Burcu Zeydan; Val J. Lowe; Ross R. Reichard; Scott A. Przybelski; Timothy G. Lesnick; Christopher G. Schwarz; Matthew L. Senjem; Jeffrey L. Gunter; Joseph E. Parisi; Mary M. Machulda; Prashanthi Vemuri; Michelle M. Mielke; David S. Knopman; Ronald C. Petersen; Clifford R. Jack; Orhun H. Kantarci; Kejal Kantarci

    To investigate β‐amyloid and tau depositions using Pittsburgh compound B (PiB) PET and AV1451 tau PET imaging in aging multiple sclerosis (MS) patients.

    更新日期:2020-01-23
  • Classification Accuracy of Transcranial Magnetic Stimulation for the Diagnosis of Neurodegenerative Dementias
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-23
    Alberto Benussi; Mario Grassi; Fernando Palluzzi; Giacomo Koch; Vincenzo Di Lazzaro; Raffaele Nardone; Valentina Cantoni; Valentina Dell'Era; Enrico Premi; Alessandro Martorana; Francesco di Lorenzo; Sonia Bonnì; Federico Ranieri; Fioravante Capone; Gabriella Musumeci; Maria Sofia Cotelli; Alessandro Padovani; Barbara Borroni

    Transcranial magnetic stimulation (TMS) has been suggested as a reliable, noninvasive, and inexpensive tool for the diagnosis of neurodegenerative dementias. In this study, we assessed the classification performance of TMS parameters in the differential diagnosis of common neurodegenerative disorders, including Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD).

    更新日期:2020-01-23
  • A Novel Recessive TNNT1 Congenital Core‐Rod Myopathy in French Canadians
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-22
    David Pellerin; Asli Aykanat; Benjamin Ellezam; Emily C. Troiano; Jason Karamchandani; Marie‐Josée Dicaire; Marc Petitclerc; Rebecca Robertson; Xavier Allard‐Chamard; Denis Brunet; Chamindra G. Konersman; Jean Mathieu; Jodi Warman Chardon; Vandana A. Gupta; Alan H. Beggs; Bernard Brais; Nicolas Chrestian

    Recessive null variants of the slow skeletal muscle troponin T1 (TNNT1) gene are a rare cause of nemaline myopathy that is fatal in infancy due to respiratory insufficiency. Muscle biopsy shows rods and fiber type disproportion. We report on four French Canadians with a novel form of recessive congenital TNNT1 core‐rod myopathy.

    更新日期:2020-01-23
  • Correction: Factors associated with successful antipsychotic dose reduction in schizophrenia: a systematic review of prospective clinical trials and meta-analysis of randomized controlled trials
    Neuropsychopharmacology (IF 7.160) Pub Date : 2020-01-23
    Hideaki Tani; Shotaro Takasu; Hiroyuki Uchida; Takefumi Suzuki; Masaru Mimura; Hiroyoshi Takeuchi

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-01-23
  • Non-gated cardiac CT angiography for detection of cardio-aortic sources of embolism in the acute phase of ischaemic stroke
    J. Neurol. Neurosurg. Psychiatry (IF 8.272) Pub Date : 2020-01-23
    Valeria Guglielmi; Robrecht Nils Planken; Casper Mihl; Sandra Niesen; Julie Staals; Jonathan M Coutinho; Alida A Postma

    Up to one-third of ischaemic strokes are caused by cardioembolism, which can result from atrial fibrillation (AF) or structural abnormalities.1 Establishing cardioembolic stroke aetiology is essential for secondary prevention, but cardiac thrombi may dissolve <2 hours after intravenous thrombolytic therapy (IVT).2 CT angiography (CTA) from aortic arch to intracranial vessels is necessary for patient selection for endovascular treatment (EVT) in most centres. We investigated the diagnostic yield and image quality of extending the non-ECG-gated CTA to include the heart for detection of structural cardio-aortic sources of embolism in the acute phase of ischaemic stroke, defined as within the time window for reperfusion therapy (IVT/EVT). We performed a single-centre, retrospective analysis of consecutive patients with acute ischaemic stroke with suspected large vessel occlusion (LVO) eligible for EVT who presented to the emergency department of Maastricht University Medical Center between March 2016 and April 2017. Patients underwent a non-contrast CT of the brain. Subsequently, patients with suspected LVO eligible for EVT underwent CT perfusion of the brain, and non-ECG-gated CTA from the heart to the intracranial arteries in the acute phase, as part of standard care. Patients <4.5 hours of onset of stroke without contraindications received IVT, directly after non-contrast CT and before CTA. Patients <6 hours of stroke onset with a National Institutes of Health Stroke Scale score ≥2 and/or disabling neurological deficit were eligible for EVT if LVO was identified …

    更新日期:2020-01-23
  • Minimal evidence of disease activity (MEDA) in relapsing-remitting multiple sclerosis
    J. Neurol. Neurosurg. Psychiatry (IF 8.272) Pub Date : 2020-01-23
    Luca Prosperini; Chiara Mancinelli; Shalom Haggiag; Cinzia Cordioli; Laura De Giglio; Nicola De Rossi; Simonetta Galgani; Sarah Rasia; Serena Ruggieri; Carla Tortorella; Carlo Pozzilli; Claudio Gasperini

    Objective This study aimed to define the minimal evidence of disease activity (MEDA) during treatment that can be tolerated without exposing patients with relapsing-remitting multiple sclerosis at risk of long-term disability. Methods We retrospectively collected data of patients followed up to 10 years after starting interferon beta or glatiramer acetate. Survival analyses explored the association between the long-term risk of reaching an Expanded Disability Status Scale≥6.0 and early clinical and MRI activity assessed after the first and second year of treatment. Early disease activity was classified by the so-called ‘MAGNIMS score’ ( low : no relapses and <3 new T2 lesions; medium : no relapses and ≥3 new T2 lesions or 1 relapse and 0–2 new T2 lesions; high : 1 relapse and ≥3 new T2 lesions or ≥2 relapses) and the absence or presence of contrast-enhancing lesions (CELs). Results At follow-up, 148/1036 (14.3%) patients reached the outcome: 61/685 (8.9%) with low score (reference category), 57/241 (23.7%) with medium score (HR=1.94, p=0.002) and 30/110 (27.3%) with high score (HR=2.47, p<0.001) after the first year of treatment. In the low score subgroup, the risk was further reduced in the absence (49/607, 8.1%) than in the presence of CELs (12/78, 15.4%; HR=2.11, p=0.01). No evident disease activity and low score in the absence of CELs shared the same risk (p=0.54). Similar findings were obtained even after the second year of treatment. Conclusions Early marginal MRI activity of one to two new T2 lesions, in the absence of both relapses and CELs, is associated with a minor risk of future disability, thus representing a simple and valuable definition for MEDA.

    更新日期:2020-01-23
  • Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception
    J. Neuroinflammation (IF 5.7) Pub Date : 2020-01-22
    Yongwoo Jang; Minseok Kim; Sun Wook Hwang

    Arachidonic acid-derived prostaglandins not only contribute to the development of inflammation as intercellular pro-inflammatory mediators, but also promote the excitability of the peripheral somatosensory system, contributing to pain exacerbation. Peripheral tissues undergo many forms of diseases that are frequently accompanied by inflammation. The somatosensory nerves innervating the inflamed areas experience heightened excitability and generate and transmit pain signals. Extensive studies have been carried out to elucidate how prostaglandins play their roles for such signaling at the cellular and molecular levels. Here, we briefly summarize the roles of arachidonic acid-derived prostaglandins, focusing on four prostaglandins and one thromboxane, particularly in terms of their actions on afferent nociceptors. We discuss the biosynthesis of the prostaglandins, their specific action sites, the pathological alteration of the expression levels of related proteins, the neuronal outcomes of receptor stimulation, their correlation with behavioral nociception, and the pharmacological efficacy of their regulators. This overview will help to a better understanding of the pathological roles that prostaglandins play in the somatosensory system and to a finding of critical molecular contributors to normalizing pain.

    更新日期:2020-01-23
  • A telehealth approach to improving clinical trial access for infants with tuberous sclerosis complex
    J. Neurodev. Disord. (IF 3.59) Pub Date : 2020-01-22
    Carly Hyde; Maria Pizzano; Nicole M. McDonald; Charles A. Nelson; Connie Kasari; Elizabeth A. Thiele; Shafali S. Jeste

    Research in rare genetic syndromes associated with ASD is often hampered by the wide geographic distribution of families and the presence of medical comorbidities, such as epilepsy, that may preclude travel to clinical sites. These challenges can limit the sample size and generalizability of the cohorts included in both natural history studies and clinical trials. Tuberous sclerosis complex (TSC) is a rare genetic syndrome that confers an elevated risk for autism spectrum disorder (ASD), with social communication delays identified in this population as early as 12 months of age. Early identification of risk necessitates parallel testing of early intervention, prompting the first randomized controlled clinical trial of behavioral intervention for infants with TSC (NCT03422367). However, considerable early recruitment challenges have mandated the systematic identification of enrollment barriers followed by modification of the study design to address these barriers. Caregivers were interviewed regarding barriers to enrollment (phase 1). Adaptations to the intervention were made to address these barriers (phase 2). Outcomes based on this modification to the study design were defined by enrollment rate and participant demographics. Qualitative reports from caregivers indicated that distance and time were the primary barriers to clinical trial enrollment. The intervention was then modified to a remote model, with at-home, parent-delivered intervention, and weekly video conferencing with interventionists at the study sites. Enrollment increased 10-fold (from 3 to 30 participants) within 1 year and included a more diverse and clinically representative cohort of infants. The design and implementation of more scalable methods to disseminate research remotely can substantially improve access to clinical trials in rare neurodevelopmental disorders. The lessons learned from this trial can serve as a model for future studies not only in rare conditions, but in other populations that lack adequate access, such as families with limited financial or clinical resources. Continued efforts will further refine delivery methods to enhance efficiency and ease of these delivery systems for families.

    更新日期:2020-01-23
  • Vigorous cool room treadmill training to improve walking ability in people with multiple sclerosis who use ambulatory assistive devices: a feasibility study
    BMC Neurol. (IF 2.233) Pub Date : 2020-01-22
    Augustine J. Devasahayam; Arthur R. Chaves; Wendy O. Lasisi; Marie E. Curtis; Katie P. Wadden; Liam P. Kelly; Ryan Pretty; Alice Chen; Elizabeth M. Wallack; Caitlin J. Newell; John B. Williams; Hannah Kenny; Matthew B. Downer; Jason McCarthy; Craig S. Moore; Michelle Ploughman

    Aerobic training has the potential to restore function, stimulate brain repair, and reduce inflammation in people with Multiple Sclerosis (MS). However, disability, fatigue, and heat sensitivity are major barriers to exercise for people with MS. We aimed to determine the feasibility of conducting vigorous harness-supported treadmill training in a room cooled to 16 °C (10 weeks; 3times/week) and examine the longer-term effects on markers of function, brain repair, and inflammation among those using ambulatory aids. Ten participants (9 females) aged 29 to 74 years with an Expanded Disability Status Scale ranging from 6 to 7 underwent training (40 to 65% heart rate reserve) starting at 80% self-selected walking speed. Feasibility of conducting vigorous training was assessed using a checklist, which included attendance rates, number of missed appointments, reasons for not attending, adverse events, safety hazards during training, reasons for dropout, tolerance to training load, subjective reporting of symptom worsening during and after exercise, and physiological responses to exercise. Functional outcomes were assessed before, after, and 3 months after training. Walking ability was measured using Timed 25 Foot Walk test and on an instrumented walkway at both fast and self-selected speeds. Fatigue was measured using fatigue/energy/vitality sub-scale of 36-Item Short-Form (SF-36) Health Survey, Fatigue Severity Scale, modified Fatigue Impact Scale. Aerobic fitness (maximal oxygen consumption) was measured using maximal graded exercise test (GXT). Quality-of-life was measured using SF-36 Health Survey. Serum levels of neurotrophin (brain-derived neurotrophic factor) and cytokine (interleukin-6) were assessed before and after GXT. Eight of the ten participants completed training (attendance rates ≥ 80%). No adverse events were observed. Fast walking speed (cm/s), gait quality (double-support (%)) while walking at self-selected speed, fatigue (modified Fatigue Impact Scale), fitness (maximal workload achieved during GXT), and quality-of-life (physical functioning sub-scale of SF-36) improved significantly after training, and improvements were sustained after 3-months. Improvements in fitness (maximal respiratory exchange ratio and maximal oxygen consumption during GXT) were associated with increased brain-derived neurotrophic factor and decreased interleukin-6. Vigorous cool room training is feasible and can potentially improve walking, fatigue, fitness, and quality-of-life among people with moderate to severe MS-related disability. The study was approved by the Newfoundland and Labrador Health Research Ethics Board (reference number: 2018.088) on 11/07/2018 prior to the enrollment of first participant (retrospectively registered at ClinicalTrials.gov: NCT04066972. Registered on 26 August 2019.

    更新日期:2020-01-23
  • An update on the CNS manifestations of brain tumor polyposis syndromes
    Acta Neuropathol. (IF 18.174) Pub Date : 2020-01-22
    Byungjin Kim, Uri Tabori, Cynthia Hawkins

    Abstract Cancer predisposition syndromes are associated with an increased risk of developing primary malignancies. Here we discuss those which are associated with an increased risk of tumors of the central nervous system (CNS) and gastrointestinal (GI) tract. These can be grouped into those in which the CNS tumors predominate versus those in which the GI cancers predominate. The former include constitutional mismatch repair deficiency (CMMRD) syndrome, Li–Fraumeni syndrome (LFS), and Cowden syndrome (CS) while the latter include familial adenomatosis polyposis 1 (FAP1), Lynch syndrome and polymerase proofreading-associated polyposis syndrome (PPAP). Tumor specificity does exist as medulloblastoma occur in FAP, LFS and CMMRD while glioma are most commonly seen in all replication repair-deficient genes and LFS. Choroid plexus carcinoma is strictly observed in LFS while Cowden syndrome patients develop Lhermitte Duclos disease or meningioma. In each syndrome, specific types of low-grade and high-grade gastrointestinal cancers can occur, but these will be discussed elsewhere. Underlying cancer predisposition syndromes are important to consider when faced with brain tumors, particularly in the pediatric and young adult age groups, as identification of an underlying germ line mutation may change the upfront management of the patient and has implications for future cancer surveillance for both the patient and potentially affected family members. Considerations of family history, presence of skin lesions and consanguinity provide valuable information in identifying patients at potential increased risk.

    更新日期:2020-01-23
  • Metachromatic leukodystrophy and transplantation: remyelination, no cross‐correction
    Ann. Clin. Transl. Neur. (IF 4.656) Pub Date : 2020-01-22
    Nicole I. Wolf; Marjolein Breur; Bonnie Plug; Shanice Beerepoot; Aimee S. R. Westerveld; Diane F. van Rappard; Sharon I. de Vries; Maarten H. P. Kole; Adeline Vanderver; Marjo S. van der Knaap; Caroline A. Lindemans; Peter M. van Hasselt; Jaap J. Boelens; Ulrich Matzner; Volkmar Gieselmann; Marianna Bugiani

    In metachromatic leukodystrophy, a lysosomal storage disorder due to decreased arylsulfatase A activity, hematopoietic stem cell transplantation may stop brain demyelination and allow remyelination, thereby halting white matter degeneration. This is the first study to define the effects and therapeutic mechanisms of hematopoietic stem cell transplantation on brain tissue of transplanted metachromatic leukodystrophy patients.

    更新日期:2020-01-23
  • Near-Death Experience as a Probe to Explore (Disconnected) Consciousness
    Trends Cogn. Sci. (IF 16.173) Pub Date : 2020-01-22
    Charlotte Martial; Héléna Cassol; Steven Laureys; Olivia Gosseries

    Forty-five years ago, the first evidence of near-death experience (NDE) during comatose state was provided, setting the stage for a new paradigm for studying the neural basis of consciousness in unresponsive states. At present, the state of consciousness associated with NDEs remains an open question. In the common view, consciousness is said to disappear in a coma with the brain shutting down, but this is an oversimplification. We argue that a novel framework distinguishing awareness, wakefulness, and connectedness is needed to comprehend the phenomenon. Classical NDEs correspond to internal awareness experienced in unresponsive conditions, thereby corresponding to an episode of disconnected consciousness. Our proposal suggests new directions for NDE research, and more broadly, consciousness science.

    更新日期:2020-01-23
  • Intravenous Immunomodulatory Nanoparticle Treatment for Traumatic Brain Injury
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-22
    Sripadh Sharma; Igal Ifergan; Jonathan E. Kurz; Robert A. Linsenmeier; Dan Xu; John G. Cooper; Stephen D. Miller; John A. Kessler

    There are currently no definitive disease‐modifying therapies for traumatic brain injury (TBI). In this study, we present a strong therapeutic candidate for TBI, immunomodulatory nanoparticles (IMPs), which ablate a specific subset of hematogenous monocytes (hMos). We hypothesized that prevention of infiltration of these cells into brain acutely after TBI would attenuate secondary damage and preserve anatomic and neurologic function.

    更新日期:2020-01-23
  • Antisense Oligonucleotide Reverses Leukodystrophy in Canavan Disease Mice
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-22
    Vanessa Hull; Yan Wang; Travis Burns; Sheng Zhang; Sarah Sternbach; Jennifer McDonough; Fuzheng Guo; David Pleasure

    Marked elevation in the brain concentration of N‐acetyl‐L‐aspartate (NAA) is a characteristic feature of Canavan disease, a vacuolar leukodystrophy resulting from deficiency of the oligodendroglial NAA‐cleaving enzyme aspartoacylase. We now demonstrate that inhibiting NAA synthesis by intracisternal administration of a locked nucleic acid antisense oligonucleotide to young‐adult aspartoacylase‐deficient mice reverses their pre‐existing ataxia and diminishes cerebellar and thalamic vacuolation and Purkinje cell dendritic atrophy. ANN NEUROL 2020

    更新日期:2020-01-23
  • Co-development of a physiotherapist-delivered physical activity intervention for adults with spinal cord injury
    Spinal Cord (IF 1.898) Pub Date : 2020-01-22
    Jasmin K. Ma; Oren Cheifetz; Kendra R. Todd; Carole Chebaro; Sen Hoong Phang; Robert B. Shaw; Kyle J. Whaley; Kathleen A. Martin Ginis
    更新日期:2020-01-23
  • Assessment of the Predictive Value of Outpatient Smartphone Videos for Diagnosis of Epileptic Seizures
    JAMA Neurol. (IF 12.321) Pub Date : 2020-01-21
    William O. Tatum; Lawrence J. Hirsch; Michael A. Gelfand; Emily K. Acton; W. Curt LaFrance; Robert B. Duckrow; David K. Chen; Andrew S. Blum; John D. Hixson; Joe F. Drazkowski; Selim R. Benbadis; Gregory D. Cascino
    更新日期:2020-01-23
  • Characterization of Alzheimer Disease Biomarker Discrepancies Using Cerebrospinal Fluid Phosphorylated Tau and AV1451 Positron Emission Tomography
    JAMA Neurol. (IF 12.321) Pub Date : 2020-01-21
    Pierre-François Meyer; Alexa Pichet Binette; Julie Gonneaud; John C. S. Breitner; Sylvia Villeneuve
    更新日期:2020-01-23
  • Will We Ever Make Headway in Severe Traumatic Brain Injury Treatment Trials?
    JAMA Neurol. (IF 12.321) Pub Date : 2020-01-21
    Nick M. Murray; Zachary D. Threlkeld; Karen G. Hirsch

    Severe traumatic brain injury (STBI) is a pervasive disease that disproportionately affects young patients, elderly patients, and patients who were previously healthy. The neurologist’s roles in treating STBI are multiple, ranging from involvement in the acute critical care setting to managing the chronic sequelae that affect patients with STBI and their families. The search for effective treatments for STBI continues despite many so-called negative clinical trial results. To date, no generalizable therapy or intervention has proven to improve outcomes after STBI. In this Viewpoint, we discuss previously underrepresented factors crucial to making progress in STBI research: using precision medicine to design intervention trials and standardizing critical care management of patients with STBI, focusing specifically on differences in prognostication and withdrawal of life-sustaining therapy (WLST). Despite a historical lack of successful trials, we urge optimism because the future of clinical research in STBI is rich with opportunity.

    更新日期:2020-01-23
  • Genetic determinants of blood lipids and cerebral small vessel disease: role of high-density lipoprotein cholesterol
    Brain (IF 11.814) Pub Date : 2020-01-22
    Georgakis M, Malik R, Anderson C, et al.

    Blood lipids are causally involved in the pathogenesis of atherosclerosis, but their role in cerebral small vessel disease remains largely elusive. Here, we explored associations of genetic determinants of blood lipid levels, lipoprotein particle components, and targets for lipid-modifying drugs with small vessel disease phenotypes. We selected genetic instruments for blood levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides, for cholesterol and triglycerides components of size-defined lipoprotein particles, and for lipid-modifying drug targets based on published genome-wide association studies (up to 617 303 individuals). Applying two-sample Mendelian randomization approaches we investigated associations with ischaemic and haemorrhagic manifestations of small vessel disease [small vessel stroke: 11 710 cases, 287 067 controls; white matter hyperintensities (WMH): 10 597 individuals; intracerebral haemorrhage: 1545 cases, 1481 controls]. We applied the inverse-variance weighted method and multivariable Mendelian randomization as our main analytical approaches. Genetic predisposition to higher HDL-C levels was associated with lower risk of small vessel stroke [odds ratio (OR) per standard deviation = 0.85, 95% confidence interval (CI) = 0.78–0.92] and lower WMH volume (β = –0.07, 95% CI = −0.12 to −0.02), which in multivariable Mendelian randomization remained stable after adjustments for LDL-C and triglycerides. In analyses of lipoprotein particle components by size, we found these effects to be specific for cholesterol concentration in medium-sized high-density lipoprotein, and not large or extra-large high-density lipoprotein particles. Association estimates for intracerebral haemorrhage were negatively correlated with those for small vessel stroke and WMH volume across all lipid traits and lipoprotein particle components. HDL-C raising genetic variants in the gene locus of the target of CETP inhibitors were associated with lower risk of small vessel stroke (OR: 0.82, 95% CI = 0.75–0.89) and lower WMH volume (β = −0.08, 95% CI = −0.13 to −0.02), but a higher risk of intracerebral haemorrhage (OR: 1.64, 95% CI = 1.26–2.13). Genetic predisposition to higher HDL-C, specifically to cholesterol in medium-sized high-density lipoprotein particles, is associated with both a lower risk of small vessel stroke and lower WMH volume. These analyses indicate that HDL-C raising strategies could be considered for the prevention of ischaemic small vessel disease but the net benefit of such an approach would need to be tested in a randomized controlled trial.

    更新日期:2020-01-23
  • Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised placebo-controlled trial
    Lancet Neurol. (IF 28.755) Pub Date : 2020-01-22
    Jeremy Chataway; Floriana De Angelis; Peter Connick; Richard A Parker; Domenico Plantone; Anisha Doshi; Nevin John; Jonathan Stutters; David MacManus; Ferran Prados Carrasco; Frederik Barkhof; Sebastien Ourselin; Marie Braisher; Moira Ross; Gina Cranswick; Sue H Pavitt; Gavin Giovannoni; Claudia Angela Gandini Wheeler-Kingshott; Clive Hawkins; Basil Sharrack; Roger Bastow; Christopher J Weir; Nigel Stallard; Siddharthan Chandran; Jeremy Chataway; Claudia A.M. Gandini Wheeler-Kingshott; Floriana De Angelis; Domenico Plantone; Anisha Doshi; Nevin John; Thomas Williams; Marie Braisher; Tiggy Beyene; Vanessa Bassan; Alvin Zapata; Siddharthan Chandran; Peter Connick; Dawn Lyle; James Cameron; Daisy Mollison; Shuna Colville; Baljean Dhillon; Christopher J. Weir; Richard A. Parker; Moira Ross; Gina Cranswick; Gavin Giovannoni; Sharmilee Gnanapavan; Richard Nicholas; Waqar Rashid; Julia Aram; Helen Ford; James Overell; Carolyn Young; Heinke Arndt; Martin Duddy; Joe Guadagno; Nikolaos Evangelou; Matthew Craner; Jacqueline Palace; Jeremy Hobart; Basil Sharrack; David Paling; Clive Hawkins; Seema Kalra; Brendan McLean; Nigel Stallard; Roger Bastow
    更新日期:2020-01-23
  • Feast or famine in multiple sclerosis therapeutics
    Lancet Neurol. (IF 28.755) Pub Date : 2020-01-22
    Robert J Fox
    更新日期:2020-01-23
  • Studying Gender Diversity
    Trends Cogn. Sci. (IF 16.173) Pub Date : 2020-01-21
    Jennifer D. Rubin; S. Atwood; Kristina R. Olson

    Gender identity is a core feature of human experience, yet our understanding of gender identity is shifting with broader societal changes in recognizing and understanding gender diversity. Here we discuss recent trends and upcoming directions for this burgeoning subfield.

    更新日期:2020-01-22
  • A pharmacological chaperone improves memory by reducing Aβ and tau neuropathology in a mouse model with plaques and tangles
    Mol. Neurodegener. (IF 8.274) Pub Date : 2020-01-22
    Jian-Guo Li; Jin Chiu; Mercy Ramanjulu; Benjamin E. Blass; Domenico Praticò

    The vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex system, an ubiquitous multiprotein assembly responsible for sorting and trafficking protein cargos out of the endosomes. VPS35 can regulate APP metabolism and Aβ formation, and its levels are reduced in Alzheimer’s disease (AD) brains. We and others demonstrated that VPS35 genetic manipulation modulates the phenotype of mouse models of AD. However, the translational value of this observation remains to be investigated. Triple transgenic mice were randomized to receive a pharmacological chaperone, which stabilizes the retromer complex, and the effect on their AD-like phenotype assessed. Compared with controls, treated mice had a significant improvement in learning and memory, an elevation of VPS35 levels, and improved synaptic integrity. Additionally, the same animals had a significant decrease in Aβ levels and deposition, reduced tau phosphorylation and less astrocytes activation. Our study demonstrates that the enhancement of retromer function by pharmacological chaperones is a potentially novel and viable therapy against AD.

    更新日期:2020-01-22
  • White matter inflammation and cognitive function in a co-morbid metabolic syndrome and prodromal Alzheimer’s disease rat model
    J. Neuroinflammation (IF 5.7) Pub Date : 2020-01-21
    Nadezda Ivanova; Qingfan Liu; Cansu Agca; Yuksel Agca; Earl G. Noble; Shawn Narain Whitehead; David Floyd Cechetto

    Metabolic syndrome, the development of which is associated with high-caloric Western diet (HCD) intake, represent a risk factor for mild cognitive impairment (MCI) and dementia including Alzheimer’s disease (AD) later in life. This study aimed to investigate the effect of diet-induced metabolic disturbances on white matter neuroinflammation and cognitive function in a transgenic (TG) Fischer 344 rat carrying a human β-amyloid precursor protein (APP) gene with Swedish and Indiana mutations (APP21 TG), a model of pre-AD and MCI. TG and wildtype (WT) rats received either a HCD with 40% kJ from fat supplemented with 20% corn syrup drink or a standard diet for 12 weeks. Body weight, caloric intake, and blood pressure were measured repeatedly. End-point changes in glucose and lipid metabolism were also assessed. Open field task was used for assessment of activity; Morris water maze was used to assess spatial learning and memory. Cerebral white matter microglia and astrocytes, hippocampal neurons, and neuronal synapses were examined using immunohistochemistry. Rats maintained on the HCD developed significant obesity, visceral adiposity, dyslipidemia, and hyperinsulinemia, but did not become hypertensive. Impaired glucose tolerance was observed only in WT rats on the HCD. Total microglia number, activated OX-6+ microglia, as well as GFAP+ astrocytes located predominantly in the white matter were greater in the APP21 TG rat model in comparison to WT rats. HCD-driven metabolic perturbations further exacerbated white matter microgliosis and microglia cell activation in the APP21 TG rats and led to detectable changes in spatial reference memory in the comorbid prodromal AD and metabolic syndrome group compared to WT control rats. Neuronal density in the CA1 subregion of the hippocampus was not different between the experimental groups. Synaptic density in the CA1 and CA3 hippocampal subregions was lower in the TG rats compared to WT rats; however, there was no additional effect of the co-morbidity on this measure. These results suggest that white matter neuroinflammation might be one of the possible processes of early interaction of metabolic syndrome with MCI and pre-AD and could be one of the early brain pathologies contributing to cognitive deficits observed in mild cognitive impairment and dementia, including AD cases.

    更新日期:2020-01-22
  • Mindfulness for pain, depression, anxiety, and quality of life in people with spinal cord injury: a systematic review
    BMC Neurol. (IF 2.233) Pub Date : 2020-01-21
    Jasmine Heath Hearn; Ainslea Cross

    Populations with reduced sensory and motor function, such as spinal cord injury (SCI) are at increased risk of depression, anxiety, pain, and poorer quality of life (QoL). Mindfulness-Based Interventions (MBIs) have been developed with the aim of improving outcomes for people with SCI. To understand the value of MBIs, a systematic review was conducted pertaining to the use of MBIs, and interventions including elements of mindfulness, with people with SCI. Databases were reviewed from 1996 to October 2018 (updated January 2020). Eligibility criteria included the assessment of at least one of the common secondary consequences of SCI (i.e. risk of depression, anxiety, pain, and QoL), describe the use of mindfulness training as a component part of an intervention, or as the whole intervention. The Cochrane Collaboration Risk of Bias and The Effective Public Health Practice Project Quality Assessment Tools were utilised for quality appraisals. Two assessors appraised the studies and demonstrated good agreement (Cohen’s k = .848, p < .001). Five papers met the inclusion criteria, and demonstrated a range of results of interventions delivered individually, in a group format, in person, and online. Only one study reported significant reductions in pain-related outcomes (with moderate effect sizes), with the remaining studies (n = 4) demonstrating no change. Four studies described reductions in depressive symptoms and three reported reductions in anxiety. Despite the importance of good QoL as a goal for people with SCI, few studies (n = 2) assessed this as an outcome with no improvements reported. Study quality ranged from high to low/weak. The findings in this review provide mixed support for the use of mindfulness to improve outcomes after SCI. In particular, findings indicate that mindfulness may be particularly effective for improving symptoms of depression and anxiety. This review highlights the requirement for more rigorous, high-quality research, particularly larger randomised-controlled trials with long-term follow-up, in this area. The small number of studies included in the present review mean that conclusions drawn are preliminary and thus reflects the paucity of the research in the area to date.

    更新日期:2020-01-22
  • Extreme intracranial pressure elevation > 90 mmHg in an awake patient with primary CNS lymphoma—case report
    Acta Neurochir. (IF 1.834) Pub Date : 2020-01-22
    David Cederberg, Niklas Marklund, Henrietta Nittby Redebrandt

    Abstract We describe a patient with primary CNS lymphomas, awake despite an extreme ICP elevation. A 48-year-old woman presented with headache since 1 month, and bilateral papillary edema was observed. Magnetic resonance imaging revealed diffuse infiltration around the petrous bone. Following external ventricular drainage (EVD) placement, ICP levels of > 90 mmHg were recorded while the patient was fully awake. Cytology revealed an aggressive primary CNS lymphoma. Cerebrospinal fluid (CSF) drainage at high opening pressure levels was required. We conclude that extreme ICP elevations, treatable by CSF drainage, can be observed without a reduced level of consciousness.

    更新日期:2020-01-22
  • Preauricular retromandibular trans tympanic plate and styloid process keyhole approach to parapharyngeal lesions: a laboratory study
    Acta Neurochir. (IF 1.834) Pub Date : 2020-01-21
    Hikari Sato, Yoichi Nonaka, Udom Bawornvaraporn, Takanori Fukushima

    Abstract Background The surgical removal of the infratemporal parapharyngeal lesions (IPL) is challenging due to its anatomical complexity. Previous surgical approaches have often been too invasive and necessitated sacrifice of normal function and anatomical structures, particularly in the retromandibular nerve region. Therefore, we sought to identify an approach corridor to this area that requires less sacrifice and report an innovative approach through a retromandibular fossa route to the IPL. Methods Five cadaveric specimens were dissected bilaterally with a trans-tympanic plate and styloid process approach. These specimens were investigated microanatomically and morphometrically to examine the extent of the approach in the parapharyngeal space. The clinical application of this approach was compared to previous approaches to the IPL used in our clinical series of 20 cases. Results Using this novel approach, the inferior alveolar nerve was identified in all specimens, while the chorda tympani and lingual nerve were identified in 6 (60%) and 4 (40%) dissections, respectively. In all specimens, the petrous portion of the internal carotid artery and the exit of the lower cranial nerve were identified. The average length of the exposed lower cranial nerves was 16.6 ± 3.8 mm (range: 11–25 mm). Conclusions The described approach is feasible for accessing the IPL at the retromandibular nerve and is less invasive than conventionally used approaches.

    更新日期:2020-01-22
  • EANS Basic Brain Course (ABC): combining simulation to cadaver lab for a new concept of neurosurgical training
    Acta Neurochir. (IF 1.834) Pub Date : 2020-01-21
    Alessandro Moiraghi, Alessandro Perin, Nicolas Sicky, Jelena Godjevac, Giovanni Carone, Roberta Ayadi, Tommaso Galbiati, Enrico Gambatesa, Alessandra Rocca, Claudia Fanizzi, Karl Schaller, Francesco DiMeco, Torstein R. Meling

    Abstract Background Neurosurgical training has traditionally been based on an apprenticeship model that requires considerable time and exposure to surgeries. Unfortunately, nowadays these requirements are hampered by several limitations (e.g., decreased caseload, worktime restrictions). Furthermore, teaching methods vary among residency programs due to cultural differences, monetary restrictions, and infrastructure conditions, with the possible consequence of jeopardizing residents’ training. Methods The EANS Basic Brain Course originated from a collaboration between the Besta NeuroSim Center in Milano and the Swiss Foundation for Innovation and Training in Surgery in Geneva. It was held for 5 neurosurgical residents (PGY1-3) who participated to this first pilot experience in January 2019. The main goal was to cover the very basic aspects of cranial surgery, including both technical and non-technical skills. The course was developed in modules, starting from the diagnostic paths and communication with patients (played by professional actors), then moving to practical simulation sessions, rapid theoretical lessons, and discussions based on real cases and critical ethical aspects. At the end, the candidates had cadaver lab sessions in which they practiced basic emergency procedures and craniotomies. The interaction between the participants and the faculties was created and maintained using role plays that smoothly improved the cooperation during debriefs and discussions, thus making the sessions exceedingly involving. Results At the end of the course, every trainee was able to complete the course curriculum and all the participants expressed their appreciation for this innovative format, with a particular emphasis on the time spent learning non-technical skills, confirming that they feel this to be a fundamental aspect of a comprehensive training in neurosurgery. Conclusions It is possible that this combined concept of training on technical and non-technical skills, using emerging technologies along with pedagogic techniques and cadaver dissection, may become the state-of-the-art for European Neurosurgical training programs in the next future.

    更新日期:2020-01-22
  • Quality of life effects of pain from para-lumbar- and lower extremity entrapment syndrome and carpal tunnel syndrome and comparison of the effectiveness of surgery
    Acta Neurochir. (IF 1.834) Pub Date : 2020-01-21
    Rinko Kokubo, Kyongsong Kim, Toyohiko Isu, Daijiro Morimoto, Naotaka Iwamoto, Akio Morita

    Abstract Introduction We compared the preoperative quality of life (QOL) of patients with carpal tunnel syndrome, lower extremity-, and para-lumbar entrapment syndrome, and the effect of surgery on their QOL. Patients and methods We prospectively enrolled 66 consecutive patients who underwent surgery for carpal tunnel syndrome (group 1, n = 23), lower extremity entrapment syndrome (group 2, n = 22), and para-lumbar entrapment syndrome (group 3, n = 21). Their pre- and postoperative overall health status was assessed on the Medical Outcomes Study Short-Form 36 Health Survey, v2 (SF-36). Results Except for the mental component summary, the preoperative score for items rated on the SF-36 was significantly lower in group 3 than in groups 1 and 2 (p < 0.05). In all 66 patients, the scores for bodily pain (BP) and the physical component summary (PCS) were significantly lower (p < 0.05) than the national standard, as was the score for physical functioning (PF) in groups 2 and 3. After surgery, PF of group 2 and PF, BP, and PCS of group 3 improved significantly (p < 0.05). Conclusion The detrimental QOL effects are stronger in patients with para-lumbar- or lower extremity entrapment syndrome than in patients with carpal tunnel syndrome.

    更新日期:2020-01-22
  • Detection of spreading depolarizations in a middle cerebral artery occlusion model in swine
    Acta Neurochir. (IF 1.834) Pub Date : 2020-01-15
    Modar Kentar, Martina Mann, Felix Sahm, Arturo Olivares-Rivera, Renan Sanchez-Porras, Roland Zerelles, Oliver W. Sakowitz, Andreas W. Unterberg, Edgar Santos

    Abstract Background The main objective of this study was to generate a hemodynamically stable swine model to detect spreading depolarizations (SDs) using electrocorticography (ECoG) and intrinsic optical signal (IOS) imaging and laser speckle flowmetry (LSF) after a 30-h middle cerebral artery (MCA) occlusion (MCAo) in German Landrace Swine. Methods A total of 21 swine were used. The study comprised a training group (group 1, n = 7), a group that underwent bilateral craniectomy and MCAo (group 2, n = 10) and a group used for 2,3,5-triphenyltetrazolium (TTC) staining (group 3, n = 5). Results In group 2, nine animals that underwent MCAo survived for 30 h, and one animal survived for 12 h. We detected MCA variants with 2 to 4 vessels. In all cases, all of the MCAs were occluded. The intensity changes exhibited by IOS and LSF after clipping were closely correlated and indicated a lower blood volume and reduced blood flow in the middle cerebral artery territory. Using IOS, we detected a mean of 2.37 ± (STD) 2.35 SDs/h. Using ECoG, we detected a mean of 0.29 ± (STD) 0.53 SDs/h. Infarctions were diagnosed using histological analysis. TTC staining in group 3 confirmed that the MCA territory was compromised and that the anterior and posterior cerebral arteries were preserved. Conclusions We confirm the reliability of performing live monitoring of cerebral infarctions using our MCAo protocol to detect SDs.

    更新日期:2020-01-22
  • Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT): A Prospective, Multicenter Cohort Study of Imaging Selection
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-21
    Amrou Sarraj; Ameer E. Hassan; James Grotta; Clark Sitton; Gary Cutter; Chunyan Cai; Peng R. Chen; Bita Imam; Deep Pujara; Ashish Arora; Sujan Reddy; Kaushik Parsha; Roy F. Riascos; Nirav Vora; Michael Abraham; Randall Edgell; Frank Hellinger; Diogo C. Haussen; Spiros Blackburn; Haris Kamal; Andrew D. Barreto; Sheryl Martin‐Schild; Maarten Lansberg; Rishi Gupta; Sean Savitz; Gregory W. Albers

    The primary imaging modalities used to select patients for endovascular thrombectomy (EVT) are noncontrast computed tomography (CT) and CT perfusion (CTP). However, their relative utility is uncertain. We prospectively assessed CT and CTP concordance/discordance and correlated the imaging profiles on both with EVT treatment decisions and clinical outcomes.

    更新日期:2020-01-22
  • Life Course Adiposity and Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-21
    Linjing Zhang; Lu Tang; Tao Huang; Dongsheng Fan

    Observational studies have indicated that life course adiposity is associated with amyotrophic lateral sclerosis (ALS). However, whether such an association reflects causality remains unclear. We aimed to determine whether life course adiposity such as birth weight (BW), childhood body mass index (BMI), adult BMI, body fat percentage (BF%), and waist‐to‐hip ratio (WHR) have causal effects on ALS.

    更新日期:2020-01-22
  • Transcutaneous contrast-enhanced ultrasound imaging of the posttraumatic spinal cord
    Spinal Cord (IF 1.898) Pub Date : 2020-01-21
    Zin Z. Khaing; Lindsay N. Cates; Jeffrey E. Hyde; Ryan Hammond; Matthew Bruce; Christoph P. Hofstetter
    更新日期:2020-01-22
  • Use of oral third generation cephalosporins and quinolones and occurrence of antibiotic-resistant strains in the neurogenic bladder (NB) outpatient setting: a retrospective chart audit
    Spinal Cord (IF 1.898) Pub Date : 2020-01-21
    Koichi Kitagawa; Katsumi Shigemura; Masashi Nomi; Nozomi Takami; Naoki Yamada; Masato Fujisawa
    更新日期:2020-01-22
  • Activation of D1 receptors affects human reactivity and flexibility to valued cues
    Neuropsychopharmacology (IF 7.160) Pub Date : 2020-01-21
    Alexander Soutschek; Rouba Kozak; Nicholas de Martinis; William Howe; Christopher J. Burke; Ernst Fehr; Alexander Jetter; Philippe N. Tobler

    Reward-predicting cues motivate goal-directed behavior, but in unstable environments humans must also be able to flexibly update cue-reward associations. While the capacity of reward cues to trigger motivation (‘reactivity’) as well as flexibility in cue-reward associations have been linked to the neurotransmitter dopamine in humans, the specific contribution of the dopamine D1 receptor family to these behaviors remained elusive. To fill this gap, we conducted a randomized, placebo-controlled, double-blind pharmacological study testing the impact of three different doses of a novel D1 agonist (relative to placebo) on reactivity to reward-predicting cues (Pavlovian-to-instrumental transfer) and flexibility of cue-outcome associations (reversal learning). We observed that the impact of the D1 agonist crucially depended on baseline working memory functioning, which has been identified as a proxy for baseline dopamine synthesis capacity. Specifically, increasing D1 receptor stimulation strengthened Pavlovian-to-instrumental transfer in individuals with high baseline working memory capacity. In contrast, higher doses of the D1 agonist improved reversal learning only in individuals with low baseline working memory functioning. Our findings suggest a crucial and baseline-dependent role of D1 receptor activation in controlling both cue reactivity and the flexibility of cue-reward associations.

    更新日期:2020-01-22
  • Effect of rovatirelin in patients with cerebellar ataxia: two randomised double-blind placebo-controlled phase 3 trials
    J. Neurol. Neurosurg. Psychiatry (IF 8.272) Pub Date : 2020-01-21
    Masatoyo Nishizawa; Osamu Onodera; Akihiro Hirakawa; Yoshitaka Shimizu; Masayuki Yamada

    Objective To investigate the efficacy of rovatirelin, a thyrotropin-releasing hormone analogue, for ataxias in patients with spinocerebellar degeneration (SCD). Methods Two multicentre, randomised, double-blind, placebo-controlled phase 3 studies (KPS1301, KPS1305) enrolled patients with predominant cerebellar ataxia, including SCA6, SCA31 or cortical cerebellar atrophy. KPS1301 enrolled patients with truncal ataxia and KPS1305 enrolled patients with truncal and limb ataxia. Each study included 4 weeks of pretreatment, a 28-week or 24-week treatment period and 4 weeks of follow-up. Patients were randomised (1:1:1) to rovatirelin (1.6 or 2.4 mg) or placebo in KPS1301, and randomised (1:1) to rovatirelin 2.4 mg or placebo in KPS1305. The primary endpoint was change in Scale for the Assessment and Rating of Ataxia (SARA) total scores. Pooled analysis was performed in patients who met the SARA recruitment criteria of KPS1305. Results From October 2013 to May 2014, KPS1301 enrolled 411 patients; 374 were randomised to rovatirelin 1.6 mg (n=125), rovatirelin 2.4 mg (n=126) or placebo (n=123). From November 2016 to August 2017, KPS1305 enrolled 241 patients; 203 were randomised to rovatirelin 2.4 mg (n=101) or placebo (n=102). The primary endpoint showed no significant difference between rovatirelin and placebo in these two studies. In the pooled analysis (n=278), the difference between rovatirelin 2.4 mg (n=140) and placebo (n=138) was –0.61 (–1.64 vs –1.03; 95% CI –1.16 to –0.06; p=0.029) in the adjusted mean change in the SARA total score. Conclusions Rovatirelin is a potentially effective treatment option for SCD. Trial registration number [NCT01970098][1]; [NCT02889302][2] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01970098&atom=%2Fjnnp%2Fearly%2F2020%2F01%2F21%2Fjnnp-2019-322168.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02889302&atom=%2Fjnnp%2Fearly%2F2020%2F01%2F21%2Fjnnp-2019-322168.atom

    更新日期:2020-01-22
  • Publication records versus scientific progress
    Lancet Neurol. (IF 28.755) Pub Date : 2020-02-01
    The Lancet Neurology
    更新日期:2020-01-22
  • BEST evidence on mechanical thrombectomy for patients with vertebrobasilar occlusion
    Lancet Neurol. (IF 28.755) Pub Date : 2019-12-09
    Wouter J Schonewille

    Posterior circulation strokes account for about 20% of all ischaemic strokes, of which an estimated 15% are caused by large vessel vertebrobasilar occlusion. Basilar artery occlusion (BAO) is the most severe cause of ischaemic stroke, with outcomes much worse than those from anterior circulation occlusion. By contrast with evidence from multiple randomised controlled trials of the efficacy of endovascular treatment in acute ischaemic stroke due to anterior circulation occlusion, convincing evidence of efficacy of endovascular treatment in large vessel vertebrobasilar occlusion is still needed. , 

    更新日期:2020-01-22
  • Personalising pain control with spinal cord stimulation
    Lancet Neurol. (IF 28.755) Pub Date : 2019-12-20
    Bizhan Aarabi

    Failed back surgery syndrome (irrespective of the type of surgical intervention) is a painful disorder with a substantial affective-arousal component, rendering it hard to treat. Individuals with failed back surgery syndrome have chronic back or leg pain, or both, and this syndrome also affects their functionality, emotional wellbeing, sleep cycle, and overall wellbeing. At present, more than 20% of spinal surgeries are complicated by failed back surgery syndrome.

    更新日期:2020-01-22
  • New routes of dopaminergic drug delivery in patients with Parkinson's disease
    Lancet Neurol. (IF 28.755) Pub Date : 2019-12-06
    Angelo Antonini

    Motor fluctuations represent a therapeutic challenge in the management of Parkinson's disease. They occur as a consequence of a combination of factors, including chronic pulsatile oral levodopa treatment, progressive loss of nigrostriatal nerve terminals, and reduced endogenous dopamine storage and release capacity. As mobility becomes progressively dependent on peripheral levodopa bioavailability, physicians need to adjust medications to preserve functionality and independence. However, fluctuations are common and can manifest with both motor and non-motor symptoms, such as depression, anxiety, or pain, making their identification in clinical practice complex. Moreover, attempts to extend the effect of levodopa are limited by delayed or erratic gastric emptying, or hampered by poor tolerability. So far, extended-release levodopa formulations have failed to provide a stable levodopa concentration and a reduced pulsatile stimulation of dopamine receptors. Therefore, research has moved to identify different routes of delivering levodopa and other dopaminergic agents.

    更新日期:2020-01-22
  • International view on genetic frontotemporal dementia
    Lancet Neurol. (IF 28.755) Pub Date : 2019-12-03
    Eline Wauters; Christine Van Broeckhoven

    Frontotemporal dementia is a subtype of neurodegenerative dementia, characterised by progressive changes in behaviour and personality or language difficulties. Frontotemporal dementia has a strong genetic component, and microtubule-associated protein tau (MAPT), progranulin (GRN), and chromosome 9 open reading frame 72 (C9orf72) are the most common mutated genes. Patients with this condition show heterogeneity in clinical presentation and a wide variability in age at symptom onset, age at death, and disease duration.,  ,  This heterogeneity represents a challenge for clinical diagnostics, genetic counselling, and therapy development and evaluation.

    更新日期:2020-01-22
  • Research participation for patients with spinal cord injury
    Lancet Neurol. (IF 28.755) Pub Date : 2020-02-01
    Annemie Heselmans

    As a patient with spinal cord injury, with C1, C2, and C7 fractures with contusion of the medulla oblongata until the C2 vertebra, I have always felt lonely in my search for the right clinical trials in which I could participate. I believe it is important to have the opportunity to discuss treatment options and patients' priorities on a regular basis with the treating neurologist or rehabilitation physician. The possibility for research participation should be a normal part of these conversations. The pervasive culture that there will never be a cure for spinal cord injuries must change.

    更新日期:2020-01-22
  • Correction to Lancet Neurol 2018; 17: 597–608
    Lancet Neurol. (IF 28.755) Pub Date : 2020-02-01

    Quadri M, Mandemakers W, Grochowska MM, et al. LRP10 genetic variants in familial Parkinson's disease and dementia with Lewy bodies: a genome-wide linkage and sequencing study. Lancet Neurol 2018; 17: 597–608—The International Parkinsonism Genetic Network collaborators have now been correctly indexed in PubMed as of Jan 21, 2020.

    更新日期:2020-01-22
  • Correction to Lancet Neurol 2019; 18: 653–65
    Lancet Neurol. (IF 28.755) Pub Date : 2020-01-03

    Wilson D, Ambler G, Lee K-J, et al. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies. Lancet Neurol 2019; 18: 653–65—In this Article, the open access license has been corrected to CC BY. This correction has been made to the online version as of Jan 3, 2020.

    更新日期:2020-01-22
  • Correction to Lancet Neurol 2019; 18: 1078–79
    Lancet Neurol. (IF 28.755) Pub Date : 2020-02-01

    Knauss S, Stelzle D, Emmrich JV, Stylianou Korsnes M, Sejvar JJ, Winkler AS. An emphasis on neurology in low and middle-income countries. Lancet Neurol 2019; 18: 1078–79—In this Insight, in the figure legend, the explanation on GBD++ was incorrect, and should have been “GBD++ refers to additional neurological disorders not included in one of the other two categories (rabies, cysticercosis, neural tube defects, and neonatal encephalopathy due to birth asphyxia and trauma) and diseases which, in a certain percentage (we conservatively assumed 20%), present with neurological signs and symptoms (HIV/AIDS, malaria, low back pain, neck pain, and neglected tropical diseases other than cysticercosis and rabies)”. The surname of Dominik Stelzle has also been corrected. These corrections have been made to the online version as of Jan 21, 2020.

    更新日期:2020-01-22
  • Correction to Lancet Neurol 2020; 19: 106–08
    Lancet Neurol. (IF 28.755) Pub Date : 2020-02-01

    Wauters E, Van Broeckhoven C. International view on genetic frontotemporal dementia. Lancet Neurol 2020; 19: 106–08—In this Comment, the copyright license was incorrect. This correction has been made to the online version as of Jan 21, 2020, and the printed Comment is correct.

    更新日期:2020-01-22
  • Correction to Lancet Neurol 2020; 19: 145–56
    Lancet Neurol. (IF 28.755) Pub Date : 2020-02-01

    Moore KM, Nicholas J, Grossman M, et al. Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study. Lancet Neurol 2020; 19: 145–56—In this Article, the name of author Adeline Su Lyn Ng and the copyright license were incorrect. These corrections have been made to the online version as of Jan 21, 2020, and the printed article is correct.

    更新日期:2020-01-22
  • Anne Cross: it's a family affair
    Lancet Neurol. (IF 28.755) Pub Date : 2019-09-06
    Adrian Burton
    更新日期:2020-01-22
  • A resurrection of aducanumab for Alzheimer's disease
    Lancet Neurol. (IF 28.755) Pub Date : 2019-12-04
    Lon Schneider
    更新日期:2020-01-22
  • “No, actually it is not a headache”
    Lancet Neurol. (IF 28.755) Pub Date : 2018-11-14
    Jules Morgan
    更新日期:2020-01-22
  • Jacquelyn Cragg
    Lancet Neurol. (IF 28.755) Pub Date : 2020-02-01
    更新日期:2020-01-22
  • Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial
    Lancet Neurol. (IF 28.755) Pub Date : 2019-12-09
    Xinfeng Liu; Qiliang Dai; Ruidong Ye; Wenjie Zi; Yuxiu Liu; Huaiming Wang; Wusheng Zhu; Minmin Ma; Qin Yin; Min Li; Xinying Fan; Wen Sun; Yunfei Han; Qiushi Lv; Rui Liu; Dong Yang; Zhonghua Shi; Dequan Zheng; Xiaorong Deng; Yue Wan; Zhen Wang; Yu Geng; Xingyu Chen; Zhiming Zhou; Geng Liao; Ping Jin; Yumin Liu; Xintong Liu; Meng Zhang; Feng Zhou; Hongchao Shi; Yunfeng Zhang; Fuqiang Guo; Congguo Yin; Guozhong Niu; Mei Zhang; Xueli Cai; Qiyi Zhu; Zhonglun Chen; Yingchun Liang; Bing Li; Min Lin; Wei Wang; Haowen Xu; Xinmin Fu; Wenhua Liu; Xiguang Tian; Zili Gong; Haicun Shi; Chuanming Wang; Penghua Lv; Zhonghai Tao; Liangfu Zhu; Shiquan Yang; Wei Hu; Pingzhou Jiang; David S Liebeskind; Vitor M Pereira; Thomas Leung; Bernard Yan; Stephen Davis; Gelin Xu; Raul G Nogueira; Xinfeng Liu; Gelin Xu; Wusheng Zhu; Minmin Ma; Yunyun Xiong; Wenjie Zi; Qiliang Dai; Huaiming Wang; Ruidong Ye; Yuxiu Liu; Zhonghua Shi; Dequan Zheng; Xiaorong Deng; Yue Wan; Zhen Wang; Yu Geng; Zongjie Shi; Weihong Zheng; Xingyu Chen; Zhiming Zhou; Xianjun Huang; Geng Liao; Ping Jin; Yong Liu; Yumin Liu; Huagang Li; Xintong Liu; Meng Zhang; Feng Zhou; Hongchao Shi; Kaifu Ke; Yunfeng Zhang; Fuqiang Guo; Shu Yang; Congguo Yin; Guozhong Niu; Mei Zhang; Xueli Cai; Qiyi Zhu; Zhonglun Chen; Yingchun Liang; Bing Li; Min Lin; Hang Lin; Wei Wang; Haowen Xu; Xinmin Fu; Wei Dan; Wenhua Liu; Xiguang Tian; Lin Chen; Zili Gong; Haicun Shi; Chuanming Wang; Penghua Lv; Zhonghai Tao; Liangqun Rong; Liangfu Zhu; Shuiping Wang; Shiquan Yang; Wei Hu; Pingzhou Jiang; Jin Fan; Chengming Xing; Haifeng Li; Weiming Yang; Changqing Wang; Yong Zhang; Penghua Lv; Xiaobo Li; Vitor Pereira; Bernard Yan; David Liebeskind; Thomas Leung; Stephen Davis; Raul Nogueira
    更新日期:2020-01-22
  • Long-term safety and efficacy of closed-loop spinal cord stimulation to treat chronic back and leg pain (Evoke): a double-blind, randomised, controlled trial
    Lancet Neurol. (IF 28.755) Pub Date : 2019-12-20
    Nagy Mekhail; Robert M Levy; Timothy R Deer; Leonardo Kapural; Sean Li; Kasra Amirdelfan; Corey W Hunter; Steven M Rosen; Shrif J Costandi; Steven M Falowski; Abram H Burgher; Jason E Pope; Christopher A Gilmore; Farooq A Qureshi; Peter S Staats; James Scowcroft; Jonathan Carlson; Christopher K Kim; Michael I Yang; Thomas Stauss; Lawrence Poree; Dan Brounstein; Robert Gorman; Gerrit E. Gmel; Erin Hanson; Dean M. Karantonis; Abeer Khurram; Deidre Kiefer; Angela Leitner; Dave Mugan; Milan Obradovic; John Parker; Peter Single; Nicole Soliday
    更新日期:2020-01-22
  • Apomorphine sublingual film for off episodes in Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 study
    Lancet Neurol. (IF 28.755) Pub Date : 2019-12-06
    C Warren Olanow; Stewart A Factor; Alberto J Espay; Robert A Hauser; Holly A Shill; Stuart Isaacson; Rajesh Pahwa; Mika Leinonen; Parul Bhargava; Ken Sciarappa; Bradford Navia; David Blum; xx xx
    更新日期:2020-01-22
  • Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study
    Lancet Neurol. (IF 28.755) Pub Date : 2019-12-03
    Katrina M Moore; Jennifer Nicholas; Murray Grossman; Corey T McMillan; David J Irwin; Lauren Massimo; Vivianna M Van Deerlin; Jason D Warren; Nick C Fox; Martin N Rossor; Simon Mead; Martina Bocchetta; Bradley F Boeve; David S Knopman; Neill R Graff-Radford; Leah K Forsberg; Rosa Rademakers; Zbigniew K Wszolek; John C van Swieten; Lize C Jiskoot; Lieke H Meeter; Elise GP Dopper; Janne M Papma; Julie S Snowden; Jennifer Saxon; Matthew Jones; Stuart Pickering-Brown; Isabelle Le Ber; Agnès Camuzat; Alexis Brice; Paola Caroppo; Roberta Ghidoni; Michela Pievani; Luisa Benussi; Giuliano Binetti; Bradford C Dickerson; Diane Lucente; Samantha Krivensky; Caroline Graff; Linn Öijerstedt; Marie Fallström; Håkan Thonberg; Nupur Ghoshal; John C Morris; Barbara Borroni; Alberto Benussi; Alessandro Padovani; Daniela Galimberti; Elio Scarpini; Giorgio G Fumagalli; Ian R Mackenzie; Ging-Yuek R Hsiung; Pheth Sengdy; Adam L Boxer; Howie Rosen; Joanne B Taylor; Matthis Synofzik; Carlo Wilke; Patricia Sulzer; John R Hodges; Glenda Halliday; John Kwok; Raquel Sanchez-Valle; Albert Lladó; Sergi Borrego-Ecija; Isabel Santana; Maria Rosário Almeida; Miguel Tábuas-Pereira; Fermin Moreno; Myriam Barandiaran; Begoña Indakoetxea; Johannes Levin; Adrian Danek; James B Rowe; Thomas E Cope; Markus Otto; Sarah Anderl-Straub; Alexandre de Mendonça; Carolina Maruta; Mario Masellis; Sandra E Black; Philippe Couratier; Geraldine Lautrette; Edward D Huey; Sandro Sorbi; Benedetta Nacmias; Robert Laforce; Marie-Pier L Tremblay; Rik Vandenberghe; Philip Van Damme; Emily J Rogalski; Sandra Weintraub; Alexander Gerhard; Chiadi U Onyike; Simon Ducharme; Sokratis G Papageorgiou; Adeline Su Lyn Ng; Amy Brodtmann; Elizabeth Finger; Rita Guerreiro; Jose Bras; Jonathan D Rohrer; Carolin Heller; Rhian S Convery; Ione OC Woollacott; Rachelle M Shafei; Jonathan Graff-Radford; David T Jones; Christina M Dheel; Rodolfo Savica; Maria I Lapid; Matt Baker; Julie A Fields; Ralitza Gavrilova; Kimiko Domoto-Reilly; Jackie M Poos; Emma L Van der Ende; Jessica L Panman; Laura Donker Kaat; Harro Seelaar; Anna Richardson; Giovanni Frisoni; Anna Mega; Silvia Fostinelli; Huei-Hsin Chiang; Antonella Alberici; Andrea Arighi; Chiara Fenoglio; Hilary Heuer; Bruce Miller; Anna Karydas; Jamie Fong; Maria João Leitão; Beatriz Santiago; Diana Duro; Carlos Ferreira; Alazne Gabilondo; Maria De Arriba; Mikel Tainta; Miren Zulaica; Catarina Ferreira; Elisa Semler; Albert Ludolph; Bernhard Landwehrmeyer; Alexander E Volk; Gabriel Miltenberger; Ana Verdelho; Sónia Afonso; Maria Carmela Tartaglia; Morris Freedman; Ekaterina Rogaeva; Camilla Ferrari; Irene Piaceri; Valentina Bessi; Gemma Lombardi; Frédéric St-Onge; Marie-Claire Doré; Rose Bruffaerts; Mathieu Vandenbulcke; Jan Van den Stock; M Marsel Mesulam; Eileen Bigio; Christos Koros; John Papatriantafyllou; Christos Kroupis; Leonidas Stefanis; Christien Shoesmith; Erik Robertson; Giovanni Coppola; Eliana Marisa Da Silva Ramos; Daniel Geschwind
    更新日期:2020-01-22
Contents have been reproduced by permission of the publishers.
导出
全部期刊列表>>
2020新春特辑
限时免费阅读临床医学内容
ACS材料视界
科学报告最新纳米科学与技术研究
清华大学化学系段昊泓
自然科研论文编辑服务
加州大学洛杉矶分校
上海纽约大学William Glover
南开大学化学院周其林
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug