{"title":"History of cellular grafting for central nervous system repair-A clinical perspective.","authors":"Olle Lindvall","doi":"10.1016/B978-0-323-90120-8.00011-3","DOIUrl":"https://doi.org/10.1016/B978-0-323-90120-8.00011-3","url":null,"abstract":"<p><p>As late as in the 1970s, the evidence supporting that brain function might be restored by replacing dead cells by transplantation of new healthy cells was scarce in experimental animals and lacking in humans. Repairing the human brain was regarded as completely unrealistic by clinicians. Fifty years later, the situation is very different, and cellular grafting has reached patient application in several conditions affecting the CNS. The clinical studies performed so far have shown that cellular grafts can survive, grow, and function also in the diseased adult human brain. However, no proven treatment based on cell transplantation is currently available for any brain disorder. Here, the history of cellular grafting is described from a clinical perspective, including some of the preclinical work that has formed the basis for its translation to patient application. The focus is on cell transplantation for Parkinson disease, which in many ways is paving the way for this field of research. The chapter gives an account of the scientific milestones, the ups and downs, as well as the positive and negative reactions from the scientific and clinical community, and how this research field despite many obstacles has continued to move forward over more than four decades.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345473","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}
Thomas Williams, Nevin John, Anisha Doshi, Jeremy Chataway
{"title":"Adult inflammatory leukoencephalopathies.","authors":"Thomas Williams, Nevin John, Anisha Doshi, Jeremy Chataway","doi":"10.1016/B978-0-323-99209-1.00003-X","DOIUrl":"https://doi.org/10.1016/B978-0-323-99209-1.00003-X","url":null,"abstract":"<p><p>Inflammatory white matter disorders may commonly mimic genetic leukoencephalopathies. These include atypical presentations of common conditions, such as multiple sclerosis, together with rare inflammatory disorders. A structured approach to such cases is essential, together with judicious use of the many available diagnostic biomarkers. The potential for such conditions to respond to immunotherapy emphasizes the importance of an accurate and prompt diagnosis in improving patient outcomes.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345538","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":"Epidemiology of paraneoplastic neurologic syndromes.","authors":"Robert Kadish, Stacey L Clardy","doi":"10.1016/B978-0-12-823912-4.00011-6","DOIUrl":"10.1016/B978-0-12-823912-4.00011-6","url":null,"abstract":"<p><p>Paraneoplastic neurologic syndromes (PNS), initially depicted as seemingly cryptic remote manifestations of malignancy, were first described clinically in the early 20th century, with pathophysiologic correlates becoming better elucidated in the latter half of the century. There remain many questions not only about the pathophysiology but also regarding the epidemiology of these conditions. The continuous discovery of novel autoantigens and related neurologic disease has broadened the association in classical PNS to include conditions such as paraneoplastic cerebellar degeneration. It has also brought into focus several other neurologic syndromes with a putative neoplastic association. These conditions are overall rare, making it difficult to capture large numbers of patients to study, and raising the question of whether incidence is increasing over time or improved identification is driving the increased numbers of cases. With the rise and increasing use of immunotherapy for cancer treatment, the incidence of these conditions is additionally expected to rise and may present with various clinical symptoms. As we enter an era of clinical trial intervention in these conditions, much work is needed to capture more granular data on population groups defined by socioeconomic characteristics such as age, ethnicity, economic resources, and gender to optimize care and clinical trial planning.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143252","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}
Samaira Younis, Nina V Latysheva, Alexey B Danilov, Messoud Ashina
{"title":"CGRP receptor antagonists (gepants).","authors":"Samaira Younis, Nina V Latysheva, Alexey B Danilov, Messoud Ashina","doi":"10.1016/B978-0-12-823357-3.00033-1","DOIUrl":"10.1016/B978-0-12-823357-3.00033-1","url":null,"abstract":"<p><p>Small molecule calcitonin gene-related peptide (CGRP) receptor antagonists are commonly referred to as gepants. The first generation of gepants provided the first line of evidence of CGRP-mediated antimigraine medication in 2004-2011. However, further development was halted due to either lack of oral availability or concerns of hepatotoxicity. More than 15 years later, the first second generation of gepants, ubrogepant and rimegepant, are now approved for the acute treatment of migraine with or without aura. Furthermore, a novel and promising third-generation gepant, zavegepant, has recently been approved as well. In this chapter, we review the evidence supporting the effectiveness, safety, and tolerability of gepants for the acute treatment of migraine. Furthermore, we discuss the potential limitations and future directions of this class of migraine-specific medication.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671580","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":"Interventional treatments.","authors":"Narayan R Kissoon, Jason C Ray, Elspeth Hutton","doi":"10.1016/B978-0-12-823357-3.00002-1","DOIUrl":"10.1016/B978-0-12-823357-3.00002-1","url":null,"abstract":"<p><p>In migraine, when patients have failed medication management or are unable to be treated with systemic medications, minimally invasive interventions can be options used to provide pain relief. The type of intervention depends on the pain location, associated clinical features, clinical context, medical comorbidities, and response to prior injections. Interventions can vary from bedside peripheral nerve blocks to fluoroscopically guided interventions. Growing evidence is supporting the use of interventions in migraine, and judicious use can improve clinical outcomes.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671588","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":"Migraine with brainstem aura.","authors":"Robert Kaniecki","doi":"10.1016/B978-0-12-823357-3.00019-7","DOIUrl":"10.1016/B978-0-12-823357-3.00019-7","url":null,"abstract":"<p><p>Migraine with brainstem aura has been long described but remains poorly understood. Previously known as \"basilar\" or \"basilar artery\" migraine, it is an uncommon subtype of migraine with aura, one seen primarily in children, adolescents, and younger adults. The condition is characterized by migraine headache accompanied by several neurological symptoms conventionally assigned to dysfunction of brainstem structures. Initially felt to be vascular in origin, partly due to prevailing concepts of migraine pathophysiology at the time, most now believe the aura symptoms of migraine with brainstem aura are secondary to neural circuitry dysfunction. The differential diagnosis is reasonably broad, and most patients warrant investigation to exclude conditions bearing high degrees of morbidity and mortality. Neuroimaging, specifically brain MRI without contrast, is recommended for migraine with brainstem aura. Depending on the clinical presentation certain cases may require consideration of contrasted or vascular imaging, EEG, or lumbar puncture with cerebrospinal fluid analysis. Migraine prophylaxis should involve lifestyle adjustments and preventive medical therapies shown to be effective in clinical trials of migraine, following evidence-based guidelines. The acute pharmacological management of attacks of migraine with brainstem aura remains a matter of controversy. The prognosis is generally favorable. Future refinements in the diagnostic criteria might possibly enhance diagnostic specificity and improved clinical research.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671642","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":"Modification of T- and B-cell-associated immuno-pathologic mechanisms in multiple sclerosis by disease modifying therapies: Achievements and opportunities.","authors":"Joost Smolders, Jörg Hamann, Inge Huitinga","doi":"10.1016/B978-0-323-90242-7.00016-X","DOIUrl":"https://doi.org/10.1016/B978-0-323-90242-7.00016-X","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), which can clinically manifest as attacks of neurologic disability and new lesion formation, and a progression of sustained neurologic disability over time. In MS, activated B and T cells are recruited from outside the CNS, and contribute to inflammation, demyelination, and tissue damage inside the brain parenchyma. In the last decades, the treatment of MS has improved by the introduction of several disease-modifying therapies (DMTs). These drugs target generic mechanisms of lymphocyte activation and recruitment or deplete lymphocyte fractions from the circulation. This contributes to a suppression of relapses and new MS lesion formation on MRI. However, the impact on disability progression without relapses is much more variable. In addition, risk mitigation strategies are warranted to control for unwanted side effects of the attenuated immune competence induced by DMTs. In this chapter, we argue that an understanding of the impact of these DMTs on B and T cells both outside and inside the CNS can help to understand the benefits of these therapies but can also help to identify the challenges and opportunities that lie ahead for future MS therapies.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901547","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":"The hematopoietic niche and the autoreactive memory in autoimmune disorders.","authors":"Matteo Doglio, Fabio Ciceri, Chiara Bonini, Raffaella Greco","doi":"10.1016/B978-0-323-90242-7.00006-7","DOIUrl":"https://doi.org/10.1016/B978-0-323-90242-7.00006-7","url":null,"abstract":"<p><p>Hematopoiesis is a complex process that takes place inside the bone marrow, where a specialized structure, the bone marrow niche, participates in the maintenance of hematopoietic stem cell functionality. Inflammatory conditions, such as autoimmune diseases, could alter this equilibrium leading to pathologic consequences. Immune cells, which also reside in the bone marrow, directly participate in sustaining the inflammatory state in autoimmune diseases. In particular, memory lymphocytes are key players in the long-term maintenance of the immune response against self-antigens, causing tissue damage and bone marrow alterations.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901551","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}
Steven A Goldman, Robin J M Franklin, Joana Osorio
{"title":"Stem and progenitor cell-based therapy of myelin disorders.","authors":"Steven A Goldman, Robin J M Franklin, Joana Osorio","doi":"10.1016/B978-0-323-90120-8.00015-0","DOIUrl":"https://doi.org/10.1016/B978-0-323-90120-8.00015-0","url":null,"abstract":"<p><p>Much of clinical neurology is concerned with diseases of-or involving-the brain's subcortical white matter. Common to these disorders is the loss of myelin, reflecting the elimination or dysfunction of oligodendrocytes and fibrous astrocytes. As such, the introduction of glial progenitor cells, which can give rise to new oligodendrocytes and astrocytes alike, may be a feasible strategy for treating a broad variety of conditions in which white matter loss is causally involved. This review first covers the sourcing and production of human glial progenitor cells, and the preclinical evidence for their efficacy in achieving myelin restoration in vivo. It then discusses both pediatric and adult disease targets for which transplanted glial progenitors may prove of therapeutic value, those challenges that remain in the clinical application of a glial cell replacement strategy, and the clinical endpoints by which the efficacy of this approach may be assessed.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345478","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":"Foreword.","authors":"Michael J Aminoff, François Boller, Dick F Swaab","doi":"10.1016/B978-0-323-90120-8.09998-6","DOIUrl":"https://doi.org/10.1016/B978-0-323-90120-8.09998-6","url":null,"abstract":"","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345571","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}