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A Clinical Approach to Existing and Emerging Therapeutics in Neuromyelitis Optica Spectrum Disorder. 神经脊髓炎视谱障碍现有和新兴治疗方法的临床研究。
IF 5.6 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1007/s11910-023-01287-x
Heather Y F Yong, Jodie M Burton

Purpose of review: Neuromyelitis optica spectrum disorder (NMOSD) is a rare but highly disabling disease of the central nervous system. Unlike multiple sclerosis, disability in NMOSD occurs secondary to relapses that, not uncommonly, lead to blindness, paralysis, and death. Recently, newer, targeted immunotherapies have been trialed and are now in the treatment arsenal. We have endeavoured to evaluate the current state of NMOSD therapeutics.

Recent findings: This review provides a pragmatic evaluation of recent clinical trials and post-marketing data for rituximab, inebilizumab, satralizumab, eculizumab, and ravalizumab, contrasted to older agents. We also review contemporary issues such as treatment in the context of SARS-CoV2 infection and pregnancy. There has been a dramatic shift in NMOSD morbidity and mortality with earlier and improved disease recognition, diagnostic accuracy, and the advent of more effective, targeted therapies. Choosing a maintenance therapy remains nuanced depending on patient factors and accessibility. With over 100 putative agents in trials, disease-free survival is now a realistic goal for NMOSD patients.

回顾目的:神经脊髓炎视谱障碍(NMOSD)是一种罕见但高度致残的中枢神经系统疾病。与多发性硬化症不同,NMOSD的残疾继发于复发,通常会导致失明、瘫痪和死亡。最近,新的靶向免疫疗法已经进行了试验,现在已经进入治疗库。我们努力评估NMOSD治疗方法的现状。最近的发现:本综述对利妥昔单抗、伊奈比利单抗、沙伐单抗、埃曲利单抗和拉伐单抗的近期临床试验和上市后数据进行了务实的评估,并与老药进行了对比。我们还回顾了当代问题,如在SARS-CoV2感染和怀孕的背景下的治疗。随着疾病识别、诊断准确性的提高和更有效的靶向治疗的出现,NMOSD的发病率和死亡率发生了巨大变化。根据患者因素和可及性,选择维持治疗仍然是微妙的。有超过100种假定的药物正在试验中,无病生存现在是NMOSD患者的一个现实目标。
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引用次数: 0
Trigeminal Autonomic Cephalalgias and Neuralgias in Children and Adolescents: a Narrative Review. 儿童和青少年的三叉神经自主性头痛和神经痛:叙事综述。
IF 5.6 2区 医学 Q1 Medicine Pub Date : 2023-09-01 Epub Date: 2023-08-12 DOI: 10.1007/s11910-023-01288-w
Ankita Ghosh, Leena Varghese, Mark J Burish, Christina L Szperka

Purpose of review: To summarize the available literature as well as the authors' experience on trigeminal autonomic cephalalgias (TACs) and cranial neuralgias in children and adolescents.

Recent findings: While TACs and cranial neuralgias are rare in children, several recent case series have been published. TACs in children share most of the clinical features of TACs in adults. However, there are many reported cases with clinical features which overlap more than one diagnosis, suggesting that TACs may be less differentiated in youth. Indomethacin-responsive cases of cluster headache and SUNCT/SUNA have been reported in children, whereas in adults indomethacin is usually reserved for paroxysmal hemicrania and hemicrania continua. Neuralgias appear to be rare in children. Clinical features are often similar to adult cases, though clinicians should maintain a high index of suspicion for underlying causes.

综述目的:总结儿童和青少年三叉神经自主性头痛(TACs)和脑神经痛的现有文献以及作者的经验。最近的发现:虽然TAC和脑神经痛在儿童中很少见,但最近已经发表了几个病例系列。儿童TAC具有成人TAC的大部分临床特征。然而,有许多报告的病例的临床特征与一种以上的诊断重叠,这表明TAC在年轻人中的分化可能较小。据报道,儿童出现了吲哚美辛反应性丛集性头痛和SUNCT/SUNA病例,而成人则通常将吲哚美嗪用于阵发性偏头痛和持续性偏头痛。中性粒细胞增多症在儿童中似乎很少见。临床特征通常与成人病例相似,尽管临床医生应对潜在原因保持高度怀疑。
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引用次数: 0
Cognitive Aspects of COVID-19. COVID-19的认知方面。
IF 5.6 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1007/s11910-023-01286-y
Ezekiel Gonzalez-Fernandez, Juebin Huang

Purpose of review: Since the beginning of the coronavirus disease 2019 pandemic, many lasting neurological sequelae including cognitive impairment have been recognized as part of the so-called long COVID syndrome. This narrative review summarizes the cognitive aspects of COVID-19.

Recent findings: Studies have consistently identified attention, memory, and executive functions as the cognitive domains most often affected by COVID-19 infection. Many studies have also reported neuroimaging, biofluid, and neurophysiological abnormalities that could potentially reflect the pathophysiological aspects of post-COVID cognitive impairment. While patients suffering from dementia have an elevated risk of COVID-19 infection, increasing evidence has also indicated that COVID-19 infection may increase the risks of Alzheimer's disease, suggesting bidirectional relationships. Post-COVID cognitive dysfunction is a pervasive and multifaceted problem and we are surely in our infancy of understanding. Future elucidation into the long-term effects, mechanisms, and therapies will depend on a concerted effort from clinicians, researchers, patients, and policy-makers alike.

自2019年冠状病毒病大流行开始以来,包括认知障碍在内的许多持久的神经系统后遗症已被认为是所谓的长冠状病毒综合征的一部分。这篇叙述性综述总结了COVID-19的认知方面。最近的发现:研究一致认为,注意力、记忆和执行功能是最常受COVID-19感染影响的认知领域。许多研究还报告了神经影像学、生物体液和神经生理异常,这些异常可能反映了covid - 19后认知障碍的病理生理方面。虽然痴呆症患者感染COVID-19的风险较高,但越来越多的证据也表明,COVID-19感染可能会增加患阿尔茨海默病的风险,这表明两者之间存在双向关系。新冠肺炎后的认知功能障碍是一个普遍和多方面的问题,我们肯定还处于认识的起步阶段。未来对长期影响、机制和治疗的阐明将取决于临床医生、研究人员、患者和决策者的共同努力。
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引用次数: 1
Measuring Pathology in Patients with Multiple Sclerosis Using Positron Emission Tomography. 使用正电子发射断层扫描测量多发性硬化症患者的病理。
IF 5.6 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1007/s11910-023-01285-z
Matthew R Brier, Farris Taha

Purpose of review: Multiple sclerosis is characterized by a diverse and complex pathology. Clinical relapses, the hallmark of the disease, are accompanied by focal white matter lesions with intense inflammatory and demyelinating activity. Prevention of these relapses has been the major focus of pharmaceutical development, and it is now possible to dramatically reduce this inflammatory activity. Unfortunately, disability accumulation persists for many people living with multiple sclerosis owing to ongoing damage within existing lesions, pathology outside of discrete lesions, and other yet unknown factors. Understanding this complex pathological cascade will be critical to stopping progressive multiple sclerosis. Positron emission tomography uses biochemically specific radioligands to quantitatively measure pathological processes with molecular specificity. This review examines recent advances in the understanding of multiple sclerosis facilitated by positron emission tomography and identifies future avenues to expand understanding and treatment options.

Recent findings: An increasing number of radiotracers allow for the quantitative measurement of inflammatory abnormalities, de- and re-myelination, and metabolic disruption associated with multiple sclerosis. The studies have identified contributions of ongoing, smoldering inflammation to accumulating tissue injury and clinical worsening. Myelin studies have quantified the dynamics of myelin loss and recovery. Lastly, metabolic changes have been found to contribute to symptom worsening. The molecular specificity facilitated by positron emission tomography in people living with multiple sclerosis will critically inform efforts to modulate the pathology leading to progressive disability accumulation. Existing studies show the power of this approach applied to multiple sclerosis. This armamentarium of radioligands allows for new understanding of how the brain and spinal cord of people is impacted by multiple sclerosis.

综述目的:多发性硬化症的特点是多样和复杂的病理。临床复发是该病的标志,伴有局灶性白质病变,伴有强烈的炎症和脱髓鞘活动。预防这些复发一直是药物开发的主要焦点,现在有可能显著减少这种炎症活动。不幸的是,许多多发性硬化症患者由于现有病变内的持续损伤、离散病变外的病理以及其他未知因素,残疾积累持续存在。了解这种复杂的病理级联将是阻止进展性多发性硬化症的关键。正电子发射断层扫描使用生化特异性放射配体来定量测量具有分子特异性的病理过程。本文回顾了近年来通过正电子发射断层扫描对多发性硬化症的理解,并确定了未来扩大理解和治疗选择的途径。最近发现:越来越多的放射性示踪剂可以定量测量炎症异常、髓鞘脱髓和再髓鞘形成以及与多发性硬化症相关的代谢紊乱。这些研究已经确定了持续的、阴燃的炎症对积累的组织损伤和临床恶化的贡献。髓磷脂研究量化了髓磷脂损失和恢复的动态。最后,已发现代谢变化有助于症状恶化。在多发性硬化症患者中,正电子发射断层扫描所促进的分子特异性将为调节导致进行性残疾积累的病理提供重要信息。现有的研究表明,这种方法适用于多发性硬化症。这种放射性配体的装备使人们对多发性硬化症如何影响人的大脑和脊髓有了新的认识。
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引用次数: 0
Polypharmacy in Multiple Sclerosis: Prevalence, Risks, and Mitigation Strategies. 多发性硬化症的多重用药:患病率、风险和缓解策略。
IF 5.6 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1007/s11910-023-01289-9
W Daniel Chapman, Megan C Herink, Michelle H Cameron, Dennis Bourdette

Purpose of review: Polypharmacy, the use of ≥ 5 medications, is common in people with multiple sclerosis and is associated with negative outcomes. The use of multiple medications is common for symptom management in people with multiple sclerosis, but risks drug-drug interactions and additive side effects. Multiple sclerosis providers should therefore focus on the appropriateness and risks versus benefits of pharmacotherapy in each patient. This review describes the prevalence and risks associated with polypharmacy in people with multiple sclerosis and offers strategies to identify and mitigate inappropriate polypharmacy.

Recent findings: Research in people with multiple sclerosis has identified risk factors and negative outcomes associated with polypharmacy. Medication class-specific investigations highlight their contribution to potentially inappropriate polypharmacy in people with multiple sclerosis. People with multiple sclerosis are at risk for inappropriate polypharmacy. Multiple sclerosis providers should review medications and consider their appropriateness and potential for deprescribing within the context of each patient.

综述目的:多重用药,即使用≥5种药物,在多发性硬化症患者中很常见,并与负面结果相关。多发性硬化症患者通常使用多种药物治疗症状,但存在药物相互作用和附加副作用的风险。因此,多发性硬化症提供者应关注每个患者药物治疗的适宜性和风险与益处。这篇综述描述了多发性硬化症患者多重用药的患病率和相关风险,并提出了识别和减轻不适当多重用药的策略。最近的发现:对多发性硬化症患者的研究已经确定了与多药相关的危险因素和负面结果。药物类别特异性调查强调了它们对多发性硬化症患者可能不适当的多药治疗的贡献。多发性硬化症患者存在不适当的多药治疗风险。多发性硬化症的提供者应该审查药物,并考虑他们的适当性和潜在的在每个病人的情况下开处方。
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引用次数: 0
Haematopoietic Stem Cell Transplantation for the Treatment of Multiple Sclerosis: Recent Advances. 造血干细胞移植治疗多发性硬化:最新进展。
IF 5.6 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1007/s11910-023-01290-2
Alice Mariottini, Eleonora De Matteis, Maria Teresa Cencioni, Paolo A Muraro

Purpose of review: Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly considered a treatment option for patients with multiple sclerosis (MS), an autoimmune demyelinating and degenerative disease of the central nervous system (CNS). AHSCT persistently suppresses inflammation and improves the disease course in large proportions of patients with relapsing-remitting (RR) MS. Aim of this article is to review the relevant new knowledge published during the last 3 years.

Recent findings: Laboratory studies reported confirmatory and new insights into the immunological and biomarker effects of AHSCT. Retrospective clinical studies confirmed excellent outcomes in RRMS, showing possible superior effectiveness over standard therapies and suggesting a possible benefit in early secondary progressive (SP) MS with inflammatory features. New data on risks of infertility and secondary autoimmunity were also reported. Further evidence on the high effectiveness and acceptable safety of AHSCT strengthens its position as a clinical option for aggressive RRMS. Further research is needed to better define its role in treatment-naïve and progressive forms of MS, ideally within randomised clinical trials (RCTs).

综述目的:自体造血干细胞移植(AHSCT)越来越被认为是多发性硬化症(MS)患者的治疗选择,多发性硬化症是一种自身免疫性脱髓鞘和中枢神经系统(CNS)退行性疾病。在很大比例的复发-缓解(RR) ms患者中,AHSCT持续抑制炎症并改善病程。本文的目的是回顾近3年来发表的相关新知识。最近的发现:实验室研究报道了AHSCT的免疫学和生物标志物效应的证实性和新的见解。回顾性临床研究证实了RRMS的良好结果,显示可能优于标准治疗的有效性,并提示可能对早期继发性进行性(SP) MS有炎症特征。还报道了关于不孕症和继发性自身免疫风险的新数据。进一步的证据表明AHSCT的高有效性和可接受的安全性加强了其作为侵袭性RRMS临床选择的地位。需要进一步的研究来更好地定义其在treatment-naïve和进展型MS中的作用,理想情况下是在随机临床试验(RCTs)中。
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引用次数: 0
The Relationship Between Sleep, Epilepsy, and Development: a Review. 睡眠、癫痫和发育的关系综述。
IF 5.6 2区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1007/s11910-023-01284-0
Annie H Roliz, Sanjeev Kothare

Purpose of review: To review the relationship between sleep, neurodevelopment, and epilepsy and potential underlying physiological mechanisms.

Recent findings: Recent studies have advanced our understanding of the role of sleep in early brain development and epilepsy. Epileptogenesis has been proposed to occur when there is a failure of normal adaptive processes of synaptic and homeostatic plasticity. This sleep-dependent transformation may explain the cognitive impairment seen in epilepsy, especially when occurring early in life. The glymphatic system, a recently discovered waste clearance system of the central nervous system, has been described as a potential mechanism underlying the relationship between sleep and seizures and may account for the common association between sleep deprivation and increased seizure risk. Epilepsy and associated sleep disturbances can critically affect brain development and neurocognition. Here we highlight recent findings on this topic and emphasize the importance of screening for sleep concerns in people with epilepsy.

综述目的:综述睡眠、神经发育和癫痫之间的关系及其潜在的生理机制。最近的发现:最近的研究提高了我们对睡眠在早期大脑发育和癫痫中的作用的理解。当突触和体内平衡可塑性的正常适应过程失败时,癫痫发生就会发生。这种依赖睡眠的转变可以解释癫痫中所见的认知障碍,特别是在生命早期发生的认知障碍。淋巴系统是最近发现的中枢神经系统的废物清除系统,被认为是睡眠和癫痫发作之间关系的潜在机制,并可能解释睡眠剥夺和癫痫发作风险增加之间的共同关联。癫痫和相关的睡眠障碍会严重影响大脑发育和神经认知。在这里,我们重点介绍了关于这一主题的最新发现,并强调了筛查癫痫患者睡眠问题的重要性。
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引用次数: 0
Adult Attention-Deficit/Hyperactivity Disorder: a Narrative Review of Biological Mechanisms, Treatments, and Outcomes. 成人注意力缺陷/多动障碍:生物学机制、治疗和结果的叙述性回顾。
IF 5.6 2区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1007/s11910-023-01280-4
Antonio F Pagán, Yazmine P Huizar, Tucker R Short, Zoe Gotcher, Adam T Schmidt

Purpose of review: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous and complex neurodevelopmental disorder related to disruptions in various neuronal structures and pathways, dopamine (DA) transporter, and receptor genes, resulting in cognitive and regulation deficits. This article reviews recent research on the biological mechanisms and markers, clinical manifestations, treatments, and outcomes of adult ADHD as well as current controversies within the field.

Recent findings: New research identifies white matter disruptions in multiple cortical pathways in adults with ADHD. New treatments for ADHD in adults such as viloxazine ER have shown preliminary effectiveness in addition to research showing transcranial direct current stimulation can be an effective treatment for adults with ADHD. Although questions exist about the effectiveness of current assessments of and treatments for adult ADHD, recent findings represent a step towards improving the quality of life and outcomes for individuals experiencing this life-long, chronic health condition.

综述目的:注意缺陷/多动障碍(ADHD)是一种异质性和复杂的神经发育障碍,与多种神经元结构和通路、多巴胺(DA)转运体和受体基因的破坏有关,导致认知和调节缺陷。本文综述了近年来关于成人ADHD的生物学机制和标志物、临床表现、治疗方法和预后的研究,以及该领域目前的争议。最新发现:新的研究发现,患有多动症的成年人的多条皮质通路中存在白质破坏。新的成人ADHD治疗方法如维洛嗪ER已经显示出初步的效果,此外还有研究表明经颅直流电刺激可以有效治疗成人ADHD。尽管目前对成人多动症的评估和治疗的有效性存在问题,但最近的研究结果表明,对于经历这种终身慢性健康状况的个人来说,朝着改善生活质量和结果迈出了一步。
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引用次数: 3
The Role of Manual Therapies in the Treatment of Headache Disorders. 手工疗法在治疗头痛疾病中的作用。
IF 5.6 2区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1007/s11910-023-01279-x
Sheena Pillai, Niushen Zhang

Purpose of review: A comprehensive headache treatment plan typically requires both medication and non-medication treatment strategies. Manual therapies offer another therapeutic approach to headache treatment. This article reviews the evidence for manual therapies in the treatment of headache disorders.

Recent findings: Current evidence shows potential benefit from myofascial trigger point injections, myofascial release, and massage for the treatment of various headache types. There is also evidence for strain counterstrain technique, ischemic compression, and spinal manipulative therapies for cervicogenic headache. Although larger randomized clinical trials are necessary for many of these modalities, recent findings show that manual therapies could be an important tool for the treatment of some headache disorders.

综述目的:一个全面的头痛治疗计划通常需要药物和非药物治疗策略。手工疗法为头痛治疗提供了另一种治疗方法。本文综述了手工疗法治疗头痛疾病的证据。最近的发现:目前的证据显示肌筋膜触发点注射、肌筋膜释放和按摩对治疗各种类型的头痛有潜在的益处。也有证据表明,应变反应变技术,缺血性压迫和脊柱手法治疗颈源性头痛。虽然这些治疗方式需要更大规模的随机临床试验,但最近的研究结果表明,手工疗法可能是治疗一些头痛疾病的重要工具。
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引用次数: 0
Neuroinflammation in Acute Ischemic and Hemorrhagic Stroke. 急性缺血性和出血性卒中的神经炎症。
IF 4.8 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-08-01 Epub Date: 2023-07-03 DOI: 10.1007/s11910-023-01282-2
Diana L Alsbrook, Mario Di Napoli, Kunal Bhatia, José Biller, Sasan Andalib, Archana Hinduja, Roysten Rodrigues, Miguel Rodriguez, Sara Y Sabbagh, Magdy Selim, Maryam Hosseini Farahabadi, Alibay Jafarli, Afshin A Divani

Purpose of review: This review aims to provide an overview of neuroinflammation in ischemic and hemorrhagic stroke, including recent findings on the mechanisms and cellular players involved in the inflammatory response to brain injury.

Recent findings: Neuroinflammation is a crucial process following acute ischemic stroke (AIS) and hemorrhagic stroke (HS). In AIS, neuroinflammation is initiated within minutes of the ischemia onset and continues for several days. In HS, neuroinflammation is initiated by blood byproducts in the subarachnoid space and/or brain parenchyma. In both cases, neuroinflammation is characterized by the activation of resident immune cells, such as microglia and astrocytes, and infiltration of peripheral immune cells, leading to the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species. These inflammatory mediators contribute to blood-brain barrier disruption, neuronal damage, and cerebral edema, promoting neuronal apoptosis and impairing neuroplasticity, ultimately exacerbating the neurologic deficit. However, neuroinflammation can also have beneficial effects by clearing cellular debris and promoting tissue repair. The role of neuroinflammation in AIS and ICH is complex and multifaceted, and further research is necessary to develop effective therapies that target this process. Intracerebral hemorrhage (ICH) will be the HS subtype addressed in this review. Neuroinflammation is a significant contributor to brain tissue damage following AIS and HS. Understanding the mechanisms and cellular players involved in neuroinflammation is essential for developing effective therapies to reduce secondary injury and improve stroke outcomes. Recent findings have provided new insights into the pathophysiology of neuroinflammation, highlighting the potential for targeting specific cytokines, chemokines, and glial cells as therapeutic strategies.

综述目的:本综述旨在概述缺血性和出血性中风中的神经炎症,包括关于脑损伤炎症反应的机制和细胞参与者的最新发现。最近的研究结果:神经炎症是急性缺血性中风(AIS)和出血性中风(HS)后的一个关键过程。在AIS中,神经炎症在缺血发作后几分钟内开始,并持续数天。在HS中,神经炎症是由蛛网膜下腔和/或脑实质中的血液副产物引发的。在这两种情况下,神经炎症的特征是激活固有免疫细胞,如小胶质细胞和星形胶质细胞,并浸润外周免疫细胞,导致促炎细胞因子、趋化因子和活性氧的释放。这些炎症介质会导致血脑屏障破坏、神经元损伤和脑水肿,促进神经元凋亡并损害神经可塑性,最终加剧神经功能缺损。然而,神经炎症也可以通过清除细胞碎片和促进组织修复而产生有益效果。神经炎症在AIS和ICH中的作用是复杂而多方面的,需要进一步的研究来开发针对这一过程的有效疗法。脑出血(ICH)将是本综述中讨论的HS亚型。神经炎症是AIS和HS后脑组织损伤的重要因素。了解神经炎症的机制和细胞参与者对于开发有效的治疗方法以减少继发性损伤和改善中风结果至关重要。最近的发现为神经炎症的病理生理学提供了新的见解,突出了靶向特定细胞因子、趋化因子和神经胶质细胞作为治疗策略的潜力。
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引用次数: 0
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