Handbook of clinical neurology最新文献_第5页

Immunotherapies in progressive multiple sclerosis. 进行性多发性硬化症的免疫治疗。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-323-90887-0.00021-3

Tradite Neziraj, Ludwig Kappos, Anne-Katrin Pröbstel

{"title":"Immunotherapies in progressive multiple sclerosis.","authors":"Tradite Neziraj, Ludwig Kappos, Anne-Katrin Pröbstel","doi":"10.1016/B978-0-323-90887-0.00021-3","DOIUrl":"10.1016/B978-0-323-90887-0.00021-3","url":null,"abstract":"Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, with both genetic and environmental risk factors. While traditionally, a relapsing and progressive disease course has been distinguished, it has increasingly become evident that elements of progression are the dominant factor for accumulating MS-related neurologic disability across all clinical courses and can be detected throughout the full disease trajectory in patients with MS. Therefore, defining the dominant pathophysiologic processes driving progression has become indispensable. Pathologic hallmarks of progressive MS include a compartmentalized inflammation within the central nervous system as well as associated neurodegenerative processes, finally leading to neuroaxonal and synaptic loss. Growing understanding of the pathophysiology has led to the development of an increasing number of targeted immunomodulatory treatment approaches for progressive MS. With the development of novel clinical trial designs and the evolution of clinical and paraclinical measures allowing accurate and rapid assessment of progression, new opportunities for personalized treatment regimens are likely to emerge.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"214 ","pages":"219-244"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

History of the brainstem-A developing concept throughout the history of medicine. 脑干史——贯穿医学史的一个发展中的概念。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-15736-3.00004-4

Eitan Lavon, Avi Ohry

引用次数: 0

Retinal ganglion cell function: ON and OFF pathways. 视网膜神经节细胞功能：ON和OFF通路。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-22193-4.00015-9

Greg D Field

{"title":"Retinal ganglion cell function: ON and OFF pathways.","authors":"Greg D Field","doi":"10.1016/B978-0-443-22193-4.00015-9","DOIUrl":"10.1016/B978-0-443-22193-4.00015-9","url":null,"abstract":"The segregation of visual signals into ON and OFF pathways represents a fundamental organizing principle of retinal processing that has been conserved across vertebrates for approximately 500 million years. This division begins at the photoreceptor-bipolar cell synapse, where distinct glutamate receptor systems create opposite responses to light increments and decrements. ON bipolar cells express metabotropic glutamate receptor 6 (mGluR6), while OFF bipolar cells utilize ionotropic AMPA/kainate receptors. These parallel pathways propagate through the inner plexiform layer's stratified architecture to retinal ganglion cells, which maintain this segregation through precise dendritic targeting or combine both signals for specialized computations. Many retinal ganglion cell types arise as paramorphic pairs with similar morphologic and functional properties, differing primarily in their preference for light increments versus decrements. However, these functionally paired ON and OFF cell types exhibit consistent asymmetries in receptive field size, temporal dynamics, and contrast sensitivity that optimize visual processing for natural scenes. These pathways show differential vulnerabilities in retinal diseases and present unique challenges for therapeutic interventions including optogenetics and prosthetic devices. Understanding ON and OFF pathway organization provides crucial insights into retinal computation, visual processing efficiency, and the neural basis of contrast detection, the foundation of visual perception.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"217 ","pages":"259-275"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neurotransmitters and retinal circuits. 神经递质和视网膜回路。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-22193-4.00002-0

Morven A Cameron

{"title":"Neurotransmitters and retinal circuits.","authors":"Morven A Cameron","doi":"10.1016/B978-0-443-22193-4.00002-0","DOIUrl":"10.1016/B978-0-443-22193-4.00002-0","url":null,"abstract":"The retinal circuits and neurotransmitters of the mammalian retina have been described in great depth over the past century. The retina is often regarded as a \"simple\" circuit that conveys light information detected in the photoreceptors through second-order intermediate cells to retinal ganglion cells that output this information to the rest of the brain. However, considerable signal processing and feature extraction occur in this simple circuit before this signal is passed down the optic nerve. The mechanisms underlying this signal processing include (i) the transformation of analog graded potentials (generated in photoreceptors and bipolar cells) to the digital spike output of retinal ganglion cells, (ii) rectification of light inputs into ON and OFF channels to aid perception of light increments and decrements, (iii) extraction/amplification of spatial and temporal features such as direction selectivity via an interplay of excitatory and inhibitory inputs, and (iv) an adaptational mechanism to change the physiology of the retina to allow it to function over>10log units of illumination. Understanding the physiology of this tissue provides important mechanistic insights into general neuronal function and may provide a \"window to the brain\" to understand central neuronal disorders.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"217 ","pages":"221-239"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retinal ganglion cells expressing melanopsin. 视网膜神经节细胞表达黑视素。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-22193-4.00016-0

Hugo Calligaro, Ouria Dkhissi-Benyahya, Satchidananda Panda

引用次数: 0

The electroretinogram as a means to study the physiology of the retina. 视网膜电图是研究视网膜生理学的一种手段。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-22212-2.00012-4

Jan Kremers, Cord Huchzermeyer, Anneka Joachimsthaler

引用次数: 0

Neuroprotective strategies for retinal disease. 视网膜疾病的神经保护策略。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-22212-2.00024-0

Guoqin Wei, Helena Pham, Emma Randall-Jarrard, Kevin Eade, Martin Friedlander

{"title":"Neuroprotective strategies for retinal disease.","authors":"Guoqin Wei, Helena Pham, Emma Randall-Jarrard, Kevin Eade, Martin Friedlander","doi":"10.1016/B978-0-443-22212-2.00024-0","DOIUrl":"10.1016/B978-0-443-22212-2.00024-0","url":null,"abstract":"Neurodegenerative diseases of the retina result from diverse insults, including genetic mutations, metabolic deficiencies, vascular compromise, and inflammatory injury. These processes converge on dysfunction of the neurovascular unit, where neurons, glia, and vascular cells cooperate to maintain retinal health. Thus, neuroprotection must be considered in a broader context that incorporates support of glial and vascular elements in addition to neurons. In this chapter, we review both classical and emerging neuroprotective strategies in retinal disease. We summarize preclinical and clinical studies of trophic factor-based approaches, including ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), fibroblast growth factor 2 (FGF2), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β (TGF-β), outlining mechanisms, efficacy, limitations, and safety. We also highlight nonclassical agents such as mesencephalic astrocyte-derived neurotrophic factor (MANF) and the lipid mediator erucamide, which act through distinct pathways to modulate stress responses and neurovascular stability. Additional approaches, including stem cell-based therapies, extracellular vesicles, metabolic supplementation, and lifestyle interventions, are discussed. Finally, we emphasize the importance of human-derived models such as retinal explants and organoids to overcome translational barriers. Collectively, these studies suggest that multimodal strategies may offer meaningful neuroprotection and preserve vision in progressive retinal disease.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"218 ","pages":"401-420"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acute retinal artery occlusions. 急性视网膜动脉闭塞。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-22212-2.00003-3

Étienne Bénard-Séguin, Brian Mac Grory, Nancy J Newman, Valérie Biousse

{"title":"Acute retinal artery occlusions.","authors":"Étienne Bénard-Séguin, Brian Mac Grory, Nancy J Newman, Valérie Biousse","doi":"10.1016/B978-0-443-22212-2.00003-3","DOIUrl":"10.1016/B978-0-443-22212-2.00003-3","url":null,"abstract":"Acute retinal artery occlusions present with sudden, painless monocular vision loss and are equivalent to cerebral strokes. The diagnosis is made on ocular fundus examination facilitated by fundus photography and optical coherence tomography. Management of acute retinal artery ischemia requires a collaborative approach among emergency department, ophthalmology, and stroke neurology providers. In the acute setting, patients should undergo a standard stroke evaluation. There are currently no widely accepted therapies for acute retinal artery occlusions. So-called \"conservative treatments,\" such as anterior chamber paracentesis, ocular massage, and hemodilution, have no benefit and should not be pursued. Recent meta-analyses and reviews from experts have suggested a possible treatment effect for intravenous tPA within 4.5hours of vision loss or intra-arterial tPA within 6hours of vision loss for patients with acute central retinal artery occlusion. Ongoing clinical trials evaluating intravenous thrombolysis within 4.5hours of vision loss will hopefully provide definite answers. In the interim, it is essential to educate providers and patients about the importance of calling emergency services when experiencing acute vision loss to ensure immediate transfer to a facility affiliated with a stroke center, where timely diagnosis, evaluation, and treatment of acute retinal ischemia can occur.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"218 ","pages":"249-269"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic mechanisms in neuroinflammatory disease of the brain: Multiple sclerosis. 脑神经炎性疾病的表观遗传机制：多发性硬化症。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-19043-8.00007-4

Lara Kular, Maja Jagodic

{"title":"Epigenetic mechanisms in neuroinflammatory disease of the brain: Multiple sclerosis.","authors":"Lara Kular, Maja Jagodic","doi":"10.1016/B978-0-443-19043-8.00007-4","DOIUrl":"https://doi.org/10.1016/B978-0-443-19043-8.00007-4","url":null,"abstract":"Multiple sclerosis (MS) is a leading cause of lifelong incurable progressive disability in young adults that results in fatigue and accumulation of physical and cognitive disability. MS is characterized by autoimmune destruction of the myelin and subsequent neuroaxonal loss. The disease is triggered by environmental factors in genetically predisposed individuals. In this chapter, we review the key findings from epigenetic studies, with a focus on the most studied modification, that is, DNA methylation. Utilization of causal analytic approaches in large cohorts provides evidence that DNA methylation mediates genetic risk in MS. Complementary genome-wide DNA methylation studies in immune cells and brain samples of people with MS highlight methylome imprints, particularly in B lymphocytes, myeloid and nervous system cells, resulting from a net effect of multiple internal and external factors. Moreover, a subtle but distinct epigenetic signature of immune cells related to neural processes is starting to emerge in association with disease progression. The outcomes of epigenetic studies provide complementary mechanistic insights into the disease initiation and progression, and might aid a better understanding of the mechanisms underpinning the disease trajectory, development of novel diagnostic and prognostic biomarkers, and ultimately improving the care of people with MS.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"219 ","pages":"399-427"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Measuring histone modifications across different cell types in the central nervous system. 测量中枢神经系统中不同细胞类型的组蛋白修饰。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-19043-8.00010-4

Gal Warhaftig, Laura M Fiori, Gustavo Turecki

{"title":"Measuring histone modifications across different cell types in the central nervous system.","authors":"Gal Warhaftig, Laura M Fiori, Gustavo Turecki","doi":"10.1016/B978-0-443-19043-8.00010-4","DOIUrl":"https://doi.org/10.1016/B978-0-443-19043-8.00010-4","url":null,"abstract":"This chapter explores recent advancements in single-cell epigenomics, with a focus on techniques for studying histone modifications and transcription factors at unprecedented resolution. Traditional bulk methods, like chromatin immunoprecipitation sequencing, have provided valuable insights but lack the ability to resolve subtle variations and rare cell types within complex tissues. Emerging single-cell techniques, such as single-cell cleavage under targets and tagmentation (scCUT&Tag), overcome these limitations by enabling precise mapping of chromatin modifications at the individual cell level. These methods allow for the simultaneous analysis of multiple epigenetic marks and their spatial distribution within a cell in a complex tissue, offering a more comprehensive understanding of gene regulation. However, challenges remain, including technical difficulties in antibody specificity, low cell input requirements, and the complexity of spatial data integration. Despite these limitations, the ongoing evolution of single-cell epigenomic technologies is revolutionizing the research of cellular heterogeneity and epigenetic regulation, with significant implications for neuroscience and other fields. This chapter provides a detailed overview of these cutting-edge methodologies, discussing their potential to uncover new dimensions of gene expression regulation in both healthy and diseased states.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"219 ","pages":"555-568"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0