Handbook of clinical neurology最新文献

{"title":"Single-cell approaches for mapping cell-type-specific epigenetic regulation.","authors":"Sheila T Nagamatsu, Melody Rivera-Hernández, Janitza L Montalvo-Ortiz","doi":"10.1016/B978-0-443-19043-8.00017-7","DOIUrl":"https://doi.org/10.1016/B978-0-443-19043-8.00017-7","url":null,"abstract":"<p><p>Epigenetic mechanisms are crucial in shaping cell identity and regulating gene function, but their patterns can vary significantly across cell types and tissues. Traditional bulk tissue analyses often obscure these differences, limiting our understanding of cell-type-specific epigenetic regulation. This chapter explores methods for single-cell isolation techniques and epigenetic assessment methodologies that enable researchers to investigate cellular heterogeneity with high precision and characterize cell-type-specific signatures. Combined with advanced epigenetic profiling techniques, these approaches provide deeper insights into tissue-specific epigenetic landscapes and their roles in development, disease, and biologic processes. Despite the challenges, such as technical limitations and data complexity, single-cell epigenetic analysis continues to refine our understanding of gene regulation and cellular function.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"219 ","pages":"537-553"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193058","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}

{"title":"Dysarthria.","authors":"Pamela M Enderby, Angela Morgan","doi":"10.1016/B978-0-443-15736-3.00005-6","DOIUrl":"10.1016/B978-0-443-15736-3.00005-6","url":null,"abstract":"<p><p>The ability to communicate pervades every aspect of life, reflecting one's personality to oneself and to others, and is critical in forming and sustaining relationships, impacting education, employment, and social engagement. This chapter provides information on dysarthria, given the role of the brainstem in articulation, intonation, prosody, and fluency. The different types of dysarthria associated with different lesions are described and methods of assessment and treatment are outlined, emphasizing the importance of a holistic approach to the management of this often overlooked, but profoundly disabling disorder.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"216 ","pages":"193-200"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147528270","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}

{"title":"Role of B cells and pathogenic autoantibodies in autoimmune CNS and PNS neurologic diseases.","authors":"Panos Stathopoulos, Marinos C Dalakas","doi":"10.1016/B978-0-323-90887-0.00003-1","DOIUrl":"10.1016/B978-0-323-90887-0.00003-1","url":null,"abstract":"<p><p>B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurologic disorders, acting, in addition to their autoantibody-secreting role, as antigen-presenting cells but also as sensors, coordinators, and regulators of the immune response. B cells can regulate the immune response, including T-cell activation through antigen presentation, production of proinflammatory cytokines (either as a bystander activation or suppression), and contribution to ectopic lymphoid aggregates. Such important functions make therapeutic depletion of B cells an attractive treatment strategy. The last decade, anti-B-cell therapies targeting B-cell surface molecules, have evolved into a rational approach for successfully treating autoimmune neurologic disorders, even when T cells seem to be the main effector cells, providing an invaluable therapeutic criterion for appreciating the key role of B cells in neurologic autoimmunities. The chapter is focused on the basic aspects of B-cell biology, addresses the different roles of B cells and autoantibodies in the pathogenesis of autoimmune and inflammatory neurologic disorders and highlights how the currently available or in the developmental stage anti-B-cell therapeutics exert their action. It specifically examines the autoantibodies of different IgG-isotypes and IgG-subclasses stressing the uniqueness of IgG4-neuroautoimmunities, and summarizes the current status of the rapidly evolving B-cell therapeutics, including CD19-CAR-T cell therapies, in multiple sclerosis, neuromyelitis-spectrum disorders, autoimmune encephalitis, stiff-person syndrome spectrum disorders, chronic autoimmune neuropathies, myasthenia gravis, and inflammatory myopathies.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"214 ","pages":"47-64"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959213","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}

{"title":"Immunobiology and immunotherapies in stiff-person syndrome and glutamic acid decarboxylase antibody-spectrum disorders: Present and future therapeutic prospects.","authors":"Marinos C Dalakas","doi":"10.1016/B978-0-323-90887-0.00009-2","DOIUrl":"10.1016/B978-0-323-90887-0.00009-2","url":null,"abstract":"<p><p>Stiff-person syndrome (SPS) is increasingly recognized as the prototypic and most common autoimmune neuronal hyperexcitability disorder that presents with stiffness in the limbs and axial muscles, stiff gait with uncontrolled falls, and episodic painful muscle spasms triggered by anxiety, task-specific phobias and startle responses, collectively leading to disability. Recent publicity has increased SPS awareness among patients and physicians, generating concerns about diagnosis, misdiagnoses, pathomechanism, and the most successful or promptly applied therapies. The paper addresses the evolving diagnostic challenges within the overlapping SPS-spectrum disorders, focusing on the progress made in SPS pathophysiology and the underlying autoimmunity; addresses the significance of antibodies against glutamic acid decarboxylase or other inhibitory synaptic antigens and the fundamentals of autoimmune neuronal hyperexcitability; and elaborates on the rationale of target-specific therapeutic interventions based on γ-aminobutyric acid -enhancing drugs and immunotherapies, stressing the need for early immunotherapy initiation to halt disability progression. The challenges of current therapies in late-onset SPS are also highlighted and an updated therapeutic scheme is provided for present and upcoming immunotherapeutic interventions for refractory disease. Finally, the challenges of applying suitable therapeutic scales in capturing the fundamentals of SPS symptomatology and objectively assessing responses to novel therapeutic trials are discussed.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"214 ","pages":"309-327"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959165","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}

{"title":"Autonomic nervous system autoimmunity and proposed immunotherapies.","authors":"Brent P Goodman","doi":"10.1016/B978-0-323-90887-0.00026-2","DOIUrl":"10.1016/B978-0-323-90887-0.00026-2","url":null,"abstract":"<p><p>Autoimmune autonomic disorders are common, though often under-recognized, and suboptimally understood. Autonomic nervous system impairment may result from immune-mediated damage to central or peripheral autonomic pathways, and typically involve both sympathetic and parasympathetic systems, as well as the enteric nervous system. Various autoimmune conditions may primarily involve the autonomic nervous system, as in autoimmune autonomic ganglionopathy associated with ganglionic nicotinic acetylcholine receptor antibodies or may involve autonomic systems as part of a multisystem neurologic process with or without underlying malignancy, or autonomic nerves may be targeted in systemic autoimmunity as is seen with Sjögren's syndrome. A careful history and diagnostic evaluation is necessary to determine the type, distribution, and severity of dysautonomia; which may be generalized or more restricted in nature. An understanding of potential autonomic features in the various autoimmune autonomic disorders can help to provide diagnostic clarity, and recognition of autonomic signs and symptoms is necessary to direct symptomatic and immunotherapeutic decisions in these patients.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"214 ","pages":"357-372"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958924","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}

{"title":"Tics in autism spectrum and in intellectual disability.","authors":"Tammy Hedderly, Osman Malik","doi":"10.1016/B978-0-443-13554-5.00027-4","DOIUrl":"10.1016/B978-0-443-13554-5.00027-4","url":null,"abstract":"<p><p>Tourette syndrome (TS) is a neuropsychiatric and a neurodevelopmental disorder often presenting alongside other neurodevelopmental conditions such as attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), learning difficulties, and dyspraxia. TS shares genetic and neurobiologic features with ASD and ADHD, suggesting common underlying mechanisms. Recent diagnostic frameworks such as the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, APA, 2013) allow for multiple co-occurring diagnoses, reflecting the complex overlap among neurodevelopmental disorders. Whilst there are several studies stating high rates of TS in ASD and vice versa, the data about the nature of tics in those with ASD is sparse; nevertheless, it shows that they are probably not different in nature to tics present in TS. Tics in individuals with ASD can be diagnostically challenging due to overlapping motor behaviors like stereotypies. Intellectual disability (ID) further complicates tic identification, given communication difficulties and co-occurring behaviors. A pragmatic, needs-focused clinical approach is recommended, emphasizing prioritisation of presenting problems over an accumulation of diagnostic labels. This strategy facilitates targeted interventions where needed. In children with ID, differentiating between tics and stereotypies is important to avoid inappropriate management.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"215 ","pages":"127-134"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112885","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}

{"title":"Obsessive-compulsive disorder in primary tic disorders and Gilles de la Tourette syndrome.","authors":"Yulia Worbe, Edouard Courtin, Pierre Burbaud","doi":"10.1016/B978-0-443-13554-5.00024-9","DOIUrl":"10.1016/B978-0-443-13554-5.00024-9","url":null,"abstract":"<p><p>This chapter provides a review of obsessive-compulsive disorder (OCD), as it manifests in primary tic disorders and Gilles de la Tourette syndrome (GTS). We examine the clinical features of OCD in GTS, focusing on how these symptoms diverge from typical OCD presentations, often blending with or mimicking tics. Key pathophysiologic mechanisms are explored, with an emphasis on the neurobiologic substrates that underlie this unique OCD subtype and distinctions from tics. Finally, the chapter discusses therapeutic approaches specifically adapted for this population, highlighting both established and emerging treatments. This chapter aims to deepen understanding of the complex interplay between OCD and GTS, offering insights into more effective clinical management and therapeutic strategies for affected individuals.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"215 ","pages":"75-84"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112881","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}

{"title":"Clinical neurophysiology of tics.","authors":"Anna Latorre, Mario Meloni, Lorenzo Rocchi","doi":"10.1016/B978-0-443-13554-5.00019-5","DOIUrl":"10.1016/B978-0-443-13554-5.00019-5","url":null,"abstract":"<p><p>Clinical neurophysiology constitutes a relevant tool for clinicians in movement disorders since it expands their characterization beyond clinically observable features and supports their diagnosis. Although the field has yet to identify a specific neurophysiologic marker for the diagnosis of tics, neurophysiology serves as a valuable tool for clinicians in differentiating tics from other hyperkinetic disorders. Beside diagnosis, recent years have witnessed the emergence of two primary domains in which neurophysiology plays a pivotal role in the realm of tic disorders: investigating the pathophysiologic foundations of tics, in an attempt to unravel the neural mechanisms that give rise to this complex movement disorder, and the application of noninvasive brain stimulation (NIBS) techniques as an avenue for therapeutic intervention. The two domains are inherently connected, as the development of noninvasive treatment methods is grounded in the mechanisms believed to underlie tics. Although the precise neurobiology of tic disorders remains incompletely understood, growing evidence implicates dysfunction within cortical-striatal-thalamic-cortical circuits as a key contributor to their pathophysiology. In this context, NIBS has been explored as a potential therapeutic approach aimed at modulating pathologic cortical hyperexcitability in specific regions, thereby enhancing inhibitory circuit engagement and ultimately alleviating tics. An intriguing alternative to transcranial stimulation is peripheral electrical nerve stimulation, which offers a distinct yet complementary mechanism of action. For instance, studies have demonstrated that rhythmic stimulation of the median nerve within the alpha frequency band can entrain neuronal oscillations in the sensorimotor cortex, leading to a measurable reduction in tic frequency and intensity. In this chapter, we will first present a comprehensive overview of clinical neurophysiology studies that have significantly contributed to our understanding of the pathophysiology of tics, and then we will offer a brief synopsis of the application of noninvasive stimulation for the treatment of tics, illustrating that clinical neurophysiology is a powerful tool that provides valuable insights into the neural underpinnings of tics and holds potential as adjunct therapy for tic management.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"215 ","pages":"201-213"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113058","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}

{"title":"Retinal imaging and artificial intelligence analysis.","authors":"James P Winebrake, Jennifer I Lim","doi":"10.1016/B978-0-443-22212-2.00011-2","DOIUrl":"10.1016/B978-0-443-22212-2.00011-2","url":null,"abstract":"<p><p>The retina, uniquely accessible as an extension of the central nervous system, plays a critical role in neurology and ophthalmology. Advances in retinal imaging technologies - including color fundus photography, optical coherence tomography, and OCT angiography - have enabled detailed, noninvasive assessment of ocular and systemic diseases. Artificial intelligence (AI), particularly deep learning, has revolutionized the analysis of these images, facilitating early detection, classification, and prognostication of conditions such as diabetic retinopathy, age-related macular degeneration, optic neuropathies, and inherited retinal diseases. AI applications extend beyond ophthalmology, offering insights into neurologic and cerebrovascular disorders through retinal biomarkers. However, challenges remain regarding dataset bias, generalizability, ethical concerns, and the \"black box\" nature of AI models. Addressing these limitations, along with integrating multimodal imaging and fostering cross-specialty collaboration, will be pivotal in ensuring that AI technology is adopted effectively and responsibly. The future will be marked by synergistic AI-human workflows to enhance diagnostic accuracy, screening scalability, and personalized patient care. As AI applications evolve, they promise to reshape retinal imaging and its intersection with neurology, expanding opportunities for early intervention and improved outcomes.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"218 ","pages":"3-12"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148100997","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}

{"title":"Retinal vein occlusion.","authors":"Tahreem A Mir, Ingrid U Scott, Stephen J Kim","doi":"10.1016/B978-0-443-22212-2.00014-8","DOIUrl":"10.1016/B978-0-443-22212-2.00014-8","url":null,"abstract":"<p><p>Retinal vein occlusion (RVO) is the second most common retinal vascular disease after diabetic retinopathy and can result in significant vision loss and ocular morbidity. Vision loss may result from hemorrhages, macular ischemia (if there is significant closure of the perifoveal capillaries), and, most commonly, macular edema. Recent advances in retinal imaging and antivascular endothelial growth factor (anti-VEGF) agents have improved the diagnosis and treatment of RVO. This has resulted in significant improvements in visual and anatomic outcomes. Anti-VEGF agents remain first-line treatment options for macular edema, with intravitreal steroids and grid laser photocoagulation as second-line treatment options. Panretinal photocoagulation is the treatment of choice for neovascular complications associated with RVO, with anti-VEGF agents as adjunct therapy. Despite therapeutic advances, RVO remains a chronic disease requiring long-term monitoring and treatment, which can sometimes result in treatment fatigue and loss to follow-up. There remains a need for long-term and more durable treatment options. The choice of treatment should be individually tailored based on discussion among the patient, family, and physician.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"218 ","pages":"271-287"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101000","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}