{"title":"Brain Metastases and Leptomeningeal Disease.","authors":"Priya Kumthekar, Emilie Le Rhun","doi":"10.1212/CON.0000000000001354","DOIUrl":"10.1212/CON.0000000000001354","url":null,"abstract":"<p><strong>Objective: </strong>Central nervous system (CNS) metastases include brain parenchymal, spinal cord, and leptomeningeal metastases. This article discusses the diagnostic and therapeutic advances of the last decade that have improved outcomes for patients with these CNS metastases.</p><p><strong>Latest developments: </strong>The diagnostic tools for CNS metastases, particularly leptomeningeal disease, have evolved over the past decade with respect to advancements in CSF analysis. Multiple medical therapies are now available for brain metastasis treatment that have shown CNS efficacy, including targeted therapies and antibody-drug conjugates. Molecular testing for CNS metastases has become more common and the repertoire of molecularly targeted therapies continues to expand. Advancements in radiation therapy, including improvements in stereotactic radiation techniques, whole-brain radiation with hippocampal avoidance, and proton beam radiation, have changed the radiation management of patients with CNS metastases. New intrathecal agents are currently being tested for the management of leptomeningeal metastases.</p><p><strong>Essential points: </strong>CNS metastases are far more common than primary brain tumors and are increasing in prevalence in the setting of improved treatments and prolonged survival in patients with systemic cancers. There have been many changes in the diagnostics and treatment of CNS metastases, yielding subsequent improvements in patient outcomes with further advancements on the horizon.</p>","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812857","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":"Neurologic Complications of Conventional Chemotherapy and Radiation Therapy.","authors":"Jennie W Taylor","doi":"10.1212/CON.0000000000001358","DOIUrl":"10.1212/CON.0000000000001358","url":null,"abstract":"<p><strong>Objective: </strong>Neurologic complications are among the most common and feared outcomes of cancer treatments. This review discusses the signs and symptoms, mechanisms, and management of the most common peripheral and central neurologic complications of chemotherapy, radiation therapy, and antiangiogenic therapy during cancer treatment and in survivors.</p><p><strong>Latest developments: </strong>The landscape of cancer treatments is evolving to include more targeted and biologic therapies, in addition to more traditional cytotoxic therapies and radiation therapy. With increasingly complex regimens and longer survival for patients with cancer, the early recognition and management of neurologic complications is key to improving the morbidity and mortality of patients living with cancer.</p><p><strong>Essential points: </strong>Neurologists should be familiar with acute central and peripheral toxicities that can occur during cancer treatment and delayed toxicities that can occur years after exposure. Neurologists should be familiar with the clinical and radiologic presentations of these complications and strategies for management.</p>","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812872","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":"2021 World Health Organization Classification of Brain Tumors.","authors":"David M Meredith, David J Pisapia","doi":"10.1212/CON.0000000000001355","DOIUrl":"10.1212/CON.0000000000001355","url":null,"abstract":"<p><strong>Objective: </strong>The classification of brain tumors is a rapidly evolving field that requires extensive integration of molecular diagnostic findings from an expanding set of platforms and assays. This article summarizes the schema presented in the 5th edition of the World Health Organization (WHO) classification of central nervous system (CNS) tumors while highlighting diagnostic molecular findings and discussing the strengths and weaknesses of commonly available testing modalities.</p><p><strong>Latest developments: </strong>Several major changes in practice were introduced with the 5th edition of the CNS WHO classification, including molecular grading of adult diffuse gliomas, the introduction of many new entities within the spectrum of pediatric gliomas and glioneuronal tumors, and the widespread adoption of methylation classes as useful or even necessary diagnostic criteria. Additionally, several revisions to nomenclature (eg, IDH-mutant gliomas) were introduced for simplicity and to disambiguate from other tumor types.</p><p><strong>Essential points: </strong>The classification of brain tumors continues to grow in complexity alongside our improved understanding of their nuanced molecular underpinnings.</p>","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812855","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":"Learning Objectives and Core Competencies.","authors":"","doi":"10.1212/CON.0000000000001365","DOIUrl":"https://doi.org/10.1212/CON.0000000000001365","url":null,"abstract":"","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405188","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":"Learning Objectives and Core Competencies.","authors":"","doi":"10.1212/CON.0000000000001365","DOIUrl":"https://doi.org/10.1212/CON.0000000000001365","url":null,"abstract":"","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307801","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":"Pediatric Neuro-oncology.","authors":"Fatema Malbari","doi":"10.1212/CON.0000000000001360","DOIUrl":"10.1212/CON.0000000000001360","url":null,"abstract":"<p><strong>Objective: </strong>This article reviews the most common pediatric brain tumors, neurocutaneous syndromes, treatment-related neurotoxicities, and the long-term outcomes of survivors.</p><p><strong>Latest developments: </strong>In the era of molecular diagnostics, the classification, management, and prognostication of pediatric brain tumors and neurocutaneous syndromes has been refined, resulting in advancements in patient management. Molecular diagnostics have been incorporated into the most recent World Health Organization 2021 classification. This knowledge has allowed for novel therapeutic approaches targeting the biology of these tumors with the intent to improve overall survival, decrease treatment-related morbidity, and improve quality of life. Advances in management have led to better survival, but mortality remains high and significant morbidity persists. Current clinical trials focus on tumor biology targeted therapy, deescalation of therapy, and multimodal intensified approaches with targeted therapy in more high-risk tumors.</p><p><strong>Essential points: </strong>Molecular diagnostics for pediatric brain tumors and neurocutaneous syndromes have led to novel therapeutic approaches targeting the biology of these tumors with the goals of improving overall survival and decreasing treatment-related morbidity. Further understanding will lead to continued refinement and improvement of tumor classification, management, and prognostication.</p>","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812880","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":"Central Nervous System Lymphoma.","authors":"Lauren Schaff","doi":"10.1212/CON.0000000000001356","DOIUrl":"10.1212/CON.0000000000001356","url":null,"abstract":"<p><strong>Objective: </strong>This article reviews the clinical presentation, diagnostic workup, staging, and treatment of primary central nervous system (CNS) lymphoma and common manifestations of secondary CNS lymphoma.</p><p><strong>Latest developments: </strong>Lymphoma can arise in the CNS de novo (primary CNS lymphoma) or as the result of systemic disease (secondary CNS lymphoma). Symptoms may include focal neurologic deficits related to the disease site, cognitive decline, and symptoms of increased intracranial pressure. Standard treatment may differ based on lymphoma subtype and location. A majority of CNS lymphoma is diffuse large B-cell subtype and exhibits aggressive behavior. First-line treatment is generally methotrexate-based polychemotherapy. Response rates to treatment are high, approximately 80% to 90% for primary CNS lymphoma, but relapse is common. Consolidation approaches including myeloablative chemotherapy followed by autologous stem cell rescue, nonmyeloablative chemotherapy, radiation, and medical maintenance regimens reduce rates of relapse. The recent development of targeted agents such as Bruton tyrosine kinase inhibitors and immunomodulatory strategies have shown promise in the treatment of CNS lymphoma. Immunotherapy in the form of checkpoint inhibitors and chimeric antigen receptor T cells is being studied. More indolent forms of lymphoma may be treated with radiation or targeted therapy.</p><p><strong>Essential points: </strong>CNS lymphoma is an uncommon but clinically meaningful manifestation of extranodal lymphoma. The diagnosis requires a high level of suspicion for rapid initiation of potentially curative treatment.</p>","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812858","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":"Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases.","authors":"Aaron Izenberg","doi":"10.1212/CON.0000000000001345","DOIUrl":"10.1212/CON.0000000000001345","url":null,"abstract":"<p><strong>Objective: </strong>This article reviews the clinical spectrum of amyotrophic lateral sclerosis (ALS), its variant presentations, and the approach to diagnosis and management. This review includes a detailed discussion of current and emerging disease-modifying therapies and the management of respiratory and bulbar manifestations of disease. An updated review of ALS genetics and pathophysiology is also provided. This article also touches on several other important motor neuron diseases.</p><p><strong>Latest developments: </strong>A new set of simplified diagnostic criteria may help identify patients at earlier stages of the disease. A coformulation of sodium phenylbutyrate and tauroursodeoxycholic acid has been shown to have a significant benefit on disease progression and survival, leading to approval by regulatory authorities in the United States and Canada. An oral formulation of edaravone and an antisense oligonucleotide to a SOD1 gene variation (tofersen) have also recently been approved by the US Food and Drug Administration (FDA). Phase 3 trials of intrathecal mesenchymal stem cells failed to meet primary end points for efficacy. Updated American Academy of Neurology quality measures for the care of patients with ALS were published in 2023.</p><p><strong>Essential points: </strong>There has been continued progress in ALS genetics, diagnosis, and disease-modifying therapies. However, we still lack a definitive biomarker or a treatment that can halt the progression or reverse the course of disease. The evolving understanding of the genetic and pathophysiologic underpinnings of disease offers promise for more effective and clinically meaningful treatments in the future.</p>","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41240813","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}
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