{"title":"The preclinical data and immunologic rationale for hematopoietic stem cell transplantation in autoimmunity.","authors":"Dimitrios Karussis, Panayiota Petrou","doi":"10.1016/B978-0-323-90242-7.00013-4","DOIUrl":"https://doi.org/10.1016/B978-0-323-90242-7.00013-4","url":null,"abstract":"<p><p>The development of autoimmune diseases (ADs) is thought to be caused by a dysfunction of the intrinsic ability of our immune system for \"self-nonself\" discrimination. Following the breakdown of \"self-tolerance,\" an orchestrated immune cascade develops, involving B- and T-lymphocytes and autoantibodies that target self-antigens. An imbalance of the regulatory immune network and a suitable genetic background, along with external (infectious and environmental) triggers, are all important contributors to the outbreak of clinical autoimmunity. Immunotherapies for ADs can be classified into treatments that are given continuously (chronic treatments) and therapies that are applied only once or intermittently, aiming to induce partial or complete reconstitution of the immune system [immune reconstitution therapies (IRTs)]. The principle underlying IRTs is based on the depletion of mature immune cells and the rebuilding of the immune system. During this process of immune reconstitution, a substantial change in the lymphocyte repertoire occurs, which may explain the impressive and long-term beneficial effects of IRTs, including the possibility of induction of tolerance to self-antigens. Hematopoietic (or bone marrow) stem cell transplantation (HSCT or BMT) represents the prototype-and the most radical type-of IRT therapy. The rationale for HSCT or BMT for the treatment of severe ADs is based on convincing proof in preclinical studies, utilizing various animal models of autoimmunity. More than 30 years' worth of pioneering experiments in various models of ADs have shown that HSCT can lead to substantial improvement or even cure of the autoimmune syndromes and induction of long-term tolerance to autoantigens. The success of treatment depends on how completely the autoantigen-reactive lymphocytes and memory cells are eradicated by the conditioning chemotherapy, which is administered in a single dose before the transplantation. The most successful conditioning methods in animal models of ADs are total body irradiation (TBI) and high-dose cyclophosphamide (CY). These preclinical studies, summarized in this review, have provided important data about the therapeutic potential of HSCT in human ADs and the associated mechanisms of action and have contributed to the formulation of guidelines for clinical applications of autologous or allogeneic HSCT/BMT in refractory autoimmunity.</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":"141901554","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 HSCT procedure (I): Mobilization, collection, manipulation, and cryopreservation of a HSC graft.","authors":"Harold Atkins","doi":"10.1016/B978-0-323-90242-7.00005-5","DOIUrl":"https://doi.org/10.1016/B978-0-323-90242-7.00005-5","url":null,"abstract":"<p><p>Most hematopoietic stem cell transplants performed for an autoimmune disease of the nervous system, use the patient's hematopoietic stem cells (HSCs). Obtaining an HSC graft is the first step of the process. This typically involves mobilization of bone marrow HSCs into the circulation using high-dose cyclophosphamide followed by filgrastim, a drug based on granulocyte colony-stimulating factor. Toxicity from these agents is usually manageable and adverse events are less severe and less frequent than those experienced during the hematopoietic stem cell transplant. Following mobilization, HSCs are collected from the circulation by leukapheresis. Some centers deplete the graft of lymphocytes using an ex vivo immunomagnetic selection procedure. HSC grafts are cryopreserved until required for the stem cell transplant. Quality testing of the graft ensures sterility and it contains sufficient HSCs and hematopoietic progenitors. The clinical and laboratory aspects of HSC graft mobilization, collection, and storage must meet standards set by national regulatory bodies and accredited by international professional standards organizations. Experienced stem cell transplant teams are important for minimizing procedural toxicity and enhancing successful collection.</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":"141901552","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":"Management of medication overuse headache.","authors":"Domenico D'Amico, Licia Grazzi, Stewart J Tepper","doi":"10.1016/B978-0-12-823357-3.00026-4","DOIUrl":"10.1016/B978-0-12-823357-3.00026-4","url":null,"abstract":"<p><p>Medication overuse headache (MOH) is a secondary headache characterized by frequent use of acute or symptomatic migraine medications at a sufficient frequency to transform patients from episodic to chronic migraine. MOH represents a significant medical problem, with a serious burden on patients' lives and on society as a whole. MOH patients often have additional comorbidities, and the clinical challenge of helping patients reduce acute medication use and revert to episodic headache can be marked. Treatment includes education and prevention; withdrawal programs; pharmacological prophylaxis; multidisciplinary therapies with behavioral and noninvasive neuromodulation options; and scheduled, frequent follow-up to prevent relapses. The advent of anti-CGRP therapy monoclonal antibodies may provide an alternative to more extensive programs for less complex patients. This review also provides guidance for which patients may benefit most from coordinated integrated programs.</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":"139671589","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":"Persistent aura, visual snow, and other visual symptoms.","authors":"Carrie E Robertson, Kathleen B Digre","doi":"10.1016/B978-0-12-823357-3.00018-5","DOIUrl":"10.1016/B978-0-12-823357-3.00018-5","url":null,"abstract":"<p><p>In neurology practice, it is common to encounter a variety of visual complaints. Historically, in the absence of known ocular pathology, epilepsy, or insult to the central nervous system, positive symptoms were assumed to be migrainous in origin. This assumption was sometimes made even in the absence of a history of migraine. In the past decade, there has been considerable effort to better delineate and study nonmigrainous visual phenomena, with the most extensive focus on a newly defined syndrome, visual snow syndrome (VSS). The heightened awareness of visual snow as a symptom and syndrome has greatly enhanced the understanding of this visual phenomenon; however, in the last few years, there has been an almost pendulous swing in clinic, with patients now being given the diagnosis of VSS for any dots or flickering they may have in their vision. To avoid clinical misdiagnosis, it is critical that we expand our understanding not just of VSS but also of underlying pathologies that may present similarly. This chapter will review classical migraine aura, persistent migraine aura, visual snow and a number of positive and negative visual complaints that are on the differential when seeing patients with suspected aura or visual snow. This is followed by an in-depth discussion on the current understanding of the presenting symptoms, pathophysiology, evaluation and management of VSS. We also outline secondary causes of visual snow.</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":"139671649","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}
Halle T McCracken, Lauren Y Thaxter, Todd A Smitherman
{"title":"Psychiatric comorbidities of migraine.","authors":"Halle T McCracken, Lauren Y Thaxter, Todd A Smitherman","doi":"10.1016/B978-0-12-823357-3.00013-6","DOIUrl":"10.1016/B978-0-12-823357-3.00013-6","url":null,"abstract":"<p><p>Migraine is commonly comorbid with psychiatric conditions, particularly major depressive disorder, anxiety disorders, and sleep disorders. The presence of psychiatric disorders can make diagnosis and treatment more challenging. Existing studies suggest that the relationship between migraine and psychiatric disorders is bidirectional, such that each disorder confers increased risk for onset of the other. Mechanisms underlying this comorbidity are largely speculative but include serotonergic dysfunction, medication overuse, allostatic load, and behavioral factors such as pain-related appraisals and unwarranted avoidance behaviors. Psychiatric comorbidities present unique clinical considerations for assessment and treatment, foremost among which is a need to routinely screen migraine patients for depression, anxiety, and insomnia. Common screening considerations and measures validated on headache patients are reviewed. Comprehensive treatment of migraine requires interventional attention also to any psychiatric comorbidities, though few randomized trials have rigorously evaluated the efficacy of pharmacologic or behavioral migraine interventions for comorbid psychiatric symptoms. Most modern antidepressants lack strong efficacy for migraine, and providers often utilize separate agents to treat migraine and any psychiatric comorbidities. Recent research on adjunctive behavioral interventions such as cognitive-behavioral therapy and acceptance-based approaches suggests they hold value in reducing psychiatric symptoms, though larger trials are needed.</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":"139671683","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":"Sciatic and tibial neuropathies.","authors":"Thomas A Miller, Douglas C Ross","doi":"10.1016/B978-0-323-90108-6.00003-X","DOIUrl":"10.1016/B978-0-323-90108-6.00003-X","url":null,"abstract":"<p><p>The sciatic nerve is the body's largest peripheral nerve. Along with their two terminal divisions (tibial and fibular), their anatomic location makes them particularly vulnerable to trauma and iatrogenic injuries. A thorough understanding of the functional anatomy is required to adequately localize lesions in this lengthy neural pathway. Proximal disorders of the nerve can be challenging to precisely localize among a range of possibilities including lumbosacral pathology, radiculopathy, or piriformis syndrome. A correct diagnosis is based upon a thorough history and physical examination, which will then appropriately direct adjunctive investigations such as imaging and electrodiagnostic testing. Disorders of the sciatic nerve and its terminal branches are disabling for patients, and expert assessment by rehabilitation professionals is important in limiting their impact. Applying techniques established in the upper extremity, surgical reconstruction of lower extremity nerve dysfunction is rapidly improving and evolving. These new techniques, such as nerve transfers, require electrodiagnostic assessment of both the injured nerve(s) as well as healthy, potential donor nerves as part of a complete neurophysiological examination.</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":"140860570","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}
Vicente González-Quintanilla, Stefan Evers, Julio Pascual
{"title":"OnabotulinumtoxinA: Discussion of the evidence for effectiveness of OnabotulinumA and its place in chronic migraine treatment.","authors":"Vicente González-Quintanilla, Stefan Evers, Julio Pascual","doi":"10.1016/B978-0-12-823357-3.00007-0","DOIUrl":"10.1016/B978-0-12-823357-3.00007-0","url":null,"abstract":"<p><p>OnabotulinumtoxinA is a potent inhibitor of muscle contraction that acts by preventing the release of acetylcholine at the neuromuscular junction. In pain states such as migraine, its mechanism of action is not yet fully elucidated and probably relates to the phenomena of central and peripheral sensitization within the trigeminal system. Migraine is a prevalent and disabling disorder and, especially in its variant of chronic migraine (CM), is associated with relevant symptomatic and socioeconomic burden, the objective of preventive treatment being to reduce the frequency, duration, or severity of migraine attacks. OnabotulinumtoxinA, administered by intramuscular injection, is approved for the prevention of CM and is among the most utilized preventive treatments in CM and fundamental to clinical practice. The efficacy and safety of OnabotulinumtoxinA in the treatment of CM have been verified by the PREEMPT 1 and 2 studies and confirmed by the real-world studies that followed, including the COMPEL, REPOSE, and CM PASS. OnabotulinumtoxinA not only reduces headache days but also leads to improvement in functioning and quality of life, thereby reducing migraine impact. Data about its pathophysiology, efficacy, and its place in CM treatment in the era of CGRP monoclonal antibodies are reviewed and discussed here.</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":"139671647","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 evolving concept of multimorbidity and migraine.","authors":"Claudia Altamura, Gianluca Coppola, Fabrizio Vernieri","doi":"10.1016/B978-0-12-823357-3.00014-8","DOIUrl":"10.1016/B978-0-12-823357-3.00014-8","url":null,"abstract":"<p><p>Migraine presents with high prevalence and similar clinical course with different disorders such as neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metabolic-endocrine, and immunological conditions, which can often cooccur themselves. Multifaceted mechanisms subtend these comorbidities with a bidirectional link. First, a shared genetic load can explain the cooccurrence. Second, comorbid pathologies can promote disproportionate energetic needs, thalamocortical network dysexcitability, and systemic transient or persistent proinflammatory state, which may trigger the activation of a broad self-protective network that includes the trigeminovascular system in conjunction with the neuroendocrine hypothalamic system. This response results in maintenance of brain homeostasis by modulating subcortical-cortical excitability, energetic balance, osmoregulation, and emotional response. In this process, the CGRP is released in the trigeminovascular system. However, the calcitonin gene-related peptide (CGRP) plays several actions also outside the brain to maintain the homeostatic needs and is involved in the physiological functions of different systems, whose disorders are associated with migraine. This aspect further increases the complexity of migraine treatment, where standard therapies often have systemic adverse effects. On the other hand, some preventives can improve comorbid conditions. In summary, we propose that migraine management should involve a multidisciplinary approach to identify and mitigate potential risk factors and comorbidity and tailor therapies individually.</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":"139671690","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 Swaab","doi":"10.1016/B978-0-12-823912-4.09998-9","DOIUrl":"10.1016/B978-0-12-823912-4.09998-9","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":"140143254","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":"Ulnar neuropathy.","authors":"Andrew Hannaford, Neil G Simon","doi":"10.1016/B978-0-323-90108-6.00006-5","DOIUrl":"10.1016/B978-0-323-90108-6.00006-5","url":null,"abstract":"<p><p>Ulnar neuropathy at the elbow is the second most common compressive neuropathy. Less common, although similarly disabling, are ulnar neuropathies above the elbow, at the forearm, and the wrist, which can present with different combinations of intrinsic hand muscle weakness and sensory loss. Electrodiagnostic studies are moderately sensitive in diagnosing ulnar neuropathy, although their ability to localize the site of nerve injury is often limited. Nerve imaging with ultrasound can provide greater localization of ulnar injury and identification of specific anatomical pathology causing nerve entrapment. Specifically, imaging can now reliably distinguish ulnar nerve entrapment under the humero-ulnar arcade (cubital tunnel) from nerve injury at the retro-epicondylar groove. Both these pathologies have historically been diagnosed as either \"ulnar neuropathy at the elbow,\" which is non-specific, or \"cubital tunnel syndrome,\" which is often erroneous. Natural history studies are few and limited, although many cases of mild-moderate ulnar neuropathy at the elbow appear to remit spontaneously. Conservative management, perineural steroid injections, and surgical release have all been studied in treating ulnar neuropathy at the elbow. Despite this, questions remain about the most appropriate management for many patients, which is reflected in the absence of management guidelines.</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":"140851356","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}