Seminars in NeurologyPub Date : 2025-05-01Epub Date: 2025-04-16DOI: 10.1055/a-2589-3825
Anne Marie Morse
{"title":"Enhancing the Management of Hypersomnia: Examining the Role of the Orexin System.","authors":"Anne Marie Morse","doi":"10.1055/a-2589-3825","DOIUrl":"10.1055/a-2589-3825","url":null,"abstract":"<p><p>Excessive daytime sleepiness (EDS) is common. However, clinical features of excessive sleepiness can have broad and variable presentations. In addition, there can be an increased likelihood of medical or psychiatric comorbidity. Examination of the networks that regulate sleep-wake and circadian control reveals a complex and intricately designed integration system. Dysregulation in the coordination, effectiveness, or efficiency of these systems can contribute to developing EDS, and inform on the endotypes observed and pharmacologic considerations for treatment. The discovery and characterization of the diurnal expression and function of orexin (hypocretin) have led to a transformed understanding of sleep-wake control and EDS, as well as its role beyond sleep. As a result, a novel drug class, orexin agonists, is anticipated to emerge for clinical use in the near future. An understanding of orexin physiology and its transdisciplinary impact is necessary to best prepare for patient selection, use, and anticipated benefit and monitoring of both expected benefits and any other health change. This study provides a review of the range of clinical features and impact of EDS, the relationship between sleep-wake, circadian and other health networks, and an examination of orexin physiology with anticipatory guidance on the potential transdisciplinary role and impact of orexin agonists.</p>","PeriodicalId":49544,"journal":{"name":"Seminars in Neurology","volume":" ","pages":"410-419"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seminars in NeurologyPub Date : 2025-05-01Epub Date: 2025-03-17DOI: 10.1055/a-2544-1482
Johnson D Pounders, Stuart J McCarter
{"title":"Sleep and Prodromal Synucleinopathies.","authors":"Johnson D Pounders, Stuart J McCarter","doi":"10.1055/a-2544-1482","DOIUrl":"10.1055/a-2544-1482","url":null,"abstract":"<p><p>α-synucleinopathies are a complex group of progressive neurodegenerative disorders with an increasingly recognized long prodromal period, during which sleep dysfunction is a hallmark. Sleep disorders during the prodromal synucleinopathy period, primarily isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and daytime hypersomnolence correlate best with the recently proposed \"body-first\" Lewy body disease progression. iRBD is the most widely recognized form of prodromal α-synucleinopathy, and patients with iRBD show abnormal α-synuclein in tissues and biofluids even in the absence of cognitive or motor symptoms. More importantly, individuals with iRBD have an elevated risk for near-term development of a clinically diagnosable symptomatic synucleinopathy. Other sleep disorders such as hypersomnia and circadian rhythm dysfunction also occur across the synucleinopathy spectrum, although their prognostic significance is less well understood than iRBD. Finally, isolated REM sleep without atonia may represent an even earlier stage of prodromal synucleinopathy, but further studies are needed.</p>","PeriodicalId":49544,"journal":{"name":"Seminars in Neurology","volume":" ","pages":"348-357"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seminars in NeurologyPub Date : 2025-05-01Epub Date: 2025-06-04DOI: 10.1055/a-2605-8706
Srija Seenivasan, Dominic Kiley, Michael Kile, J Kent Werner
{"title":"Sleep-Wake Disorders After Traumatic Brain Injury: Pathophysiology, Clinical Management, and Future.","authors":"Srija Seenivasan, Dominic Kiley, Michael Kile, J Kent Werner","doi":"10.1055/a-2605-8706","DOIUrl":"10.1055/a-2605-8706","url":null,"abstract":"<p><p>After experiencing a traumatic brain injury (TBI), the majority of patients will develop sleep-wake disorders (SWD). These can include insomnia, posttraumatic pleiosomnia (increased sleep need), excessive daytime sleepiness (EDS), obstructive and/or central sleep apnea, circadian SWD, and a variety of parasomnias. Untreated SWD may impede the recovery process and can negatively impact mood, metabolic health, cognitive function, and immune function among other processes. Importantly, these patients tend to misperceive their posttraumatic sleep problems. Consequently, interviews performed in standard clinical practice may not sufficiently capture SWD patients, potentially compromising safety and productivity. In this up-to-date review, we outline the state of current TBI-related SWD, highlighting proposed mechanisms, treatment modalities, and areas for further clinical investigation. We discuss data supporting the role of slow wave sleep in the enhancement of neural recovery and strengthening of healthy neural circuits. We also examine the utility of enhanced cohort recruitment and SWD biomarker discovery via the use of social media, smart devices, and data-sharing networks, and call for increased research in the intersection of TBI and SWD.</p>","PeriodicalId":49544,"journal":{"name":"Seminars in Neurology","volume":"45 3","pages":"383-400"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seminars in NeurologyPub Date : 2025-05-01Epub Date: 2025-04-10DOI: 10.1055/a-2559-7565
Brynn K Dredla, Tiffany J Braley
{"title":"Neuroimmunology and Sleep.","authors":"Brynn K Dredla, Tiffany J Braley","doi":"10.1055/a-2559-7565","DOIUrl":"10.1055/a-2559-7565","url":null,"abstract":"<p><p>The immune system and sleep are inextricably linked in both health and pathological conditions. Tightly regulated neuroimmune processes are critical for the physiological maintenance of healthy sleep. Reciprocally, sleep disturbances can detrimentally affect immune homeostasis and predispose to increased risk of autoimmune conditions, which themselves are bidirectionally associated with a higher risk of sleep disturbances. Autoimmune diseases of the central nervous system (CNS), particularly conditions that affect neuroanatomical regions involved in sleep homeostasis and nocturnal respiration, are associated with an increased risk sleep disorders that may impact diagnosis, clinical course, and management. This review summarizes the bidirectional relationship between sleep and immunity and highlights several exemplar autoimmune conditions of the CNS that include sleep disorders as a consequence or diagnostic feature of the disorder.</p>","PeriodicalId":49544,"journal":{"name":"Seminars in Neurology","volume":" ","pages":"420-430"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seminars in NeurologyPub Date : 2025-05-01Epub Date: 2025-03-26DOI: 10.1055/a-2566-4073
Abubaker Ibrahim, Birgit Högl, Ambra Stefani
{"title":"Sleep as the Foundation of Brain Health.","authors":"Abubaker Ibrahim, Birgit Högl, Ambra Stefani","doi":"10.1055/a-2566-4073","DOIUrl":"10.1055/a-2566-4073","url":null,"abstract":"<p><p>Sleep is a vital function, taking about one-third of a human lifetime, and is essential for achieving and maintaining brain health. From homeostatic neurophysiology to emotional and procedural memory processing to clearance of brain waste, sleep and circadian alignment remain paramount. Yet modern lifestyles and clinical practice often dismiss sleep, resulting in profound long-term repercussions. This chapter examines the roles of sleep and circadian rhythms in memory consolidation, synaptic plasticity, and clearance of metabolic waste, highlighting recent advances in neuroscience research. We explore how insufficient and disordered sleep-a public health concern-can impair cognition, escalate neurodegenerative risks, and compromise neurovascular integrity, thereby impacting brain health. These findings underscore the need for comprehensive screening for disturbed sleep and targeted interventions in clinical practice. Emerging interventions and AI-driven technologies may allow early detection and personalized and individualized treatments and improve outcomes. Overall, this chapter reaffirms that healthy sleep is indispensable at any level of neurological disease prevention-on par with the role of diet and exercise in cardiovascular health-and represents the foundation of brain health.</p>","PeriodicalId":49544,"journal":{"name":"Seminars in Neurology","volume":" ","pages":"305-316"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seminars in NeurologyPub Date : 2025-05-01Epub Date: 2025-06-26DOI: 10.1055/a-2601-9576
Pablo R Castillo
{"title":"Sleep.","authors":"Pablo R Castillo","doi":"10.1055/a-2601-9576","DOIUrl":"10.1055/a-2601-9576","url":null,"abstract":"","PeriodicalId":49544,"journal":{"name":"Seminars in Neurology","volume":"45 3","pages":"304"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seminars in NeurologyPub Date : 2025-05-01Epub Date: 2025-03-11DOI: 10.1055/a-2538-3300
David Anguizola, Alba Garcia Aragón, Brian Moncada, Diego Garcia-Borreguero
{"title":"Restless Legs Syndrome: Neurochemistry and Therapy.","authors":"David Anguizola, Alba Garcia Aragón, Brian Moncada, Diego Garcia-Borreguero","doi":"10.1055/a-2538-3300","DOIUrl":"10.1055/a-2538-3300","url":null,"abstract":"<p><p>Restless legs syndrome (RLS) is a complex sensorimotor disorder characterized by disturbances in key neurochemical pathways, including dopaminergic, glutamatergic, and adenosinergic systems. This review provides an overview of the current knowledge on RLS, including its clinical features and diagnosis, pathophysiology, and treatment (non-pharmacological and pharmacological). We examine the association between RLS and neurological disorders, genetic predispositions, and brain iron deficiency. Emerging therapies targeting glutamate and adenosine receptors, alongside established dopamine agonists and α2δ ligands, offer promising avenues for treatment.</p>","PeriodicalId":49544,"journal":{"name":"Seminars in Neurology","volume":" ","pages":"368-382"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seminars in NeurologyPub Date : 2025-05-01Epub Date: 2025-03-25DOI: 10.1055/a-2565-3317
Muna Irfan, Carlos H Schenck
{"title":"Current Perspectives on Nonrapid Eye Movement Parasomnias.","authors":"Muna Irfan, Carlos H Schenck","doi":"10.1055/a-2565-3317","DOIUrl":"10.1055/a-2565-3317","url":null,"abstract":"<p><p>Non-REM (NREM) parasomnias comprise abnormal sleep-related behaviors, autonomic nervous system function, and emotional experiences that typically arise out of deep NREM sleep. Categorized broadly as disorders of arousal (DoA), confusional arousals (CoA), sleepwalking (SW), and sleep terrors (ST) share common pathophysiological mechanisms and contributing factors. Sexsomnia is classified as a variant of CoA and SW, while sleep-related eating disorder is classified as a separate NREM parasomnia. These parasomnias emerge due to incomplete dissociation of wakefulness from NREM sleep, resulting in partial arousal characterized by decreased consciousness during motor and emotional manifestations. The behaviors emerge as a result of the interplay of various predisposing and priming factors with the additional layer of precipitating conditions. Cyclic alternating patterns and abnormal slow wave synchronization increase susceptibility to developing these behaviors in the background of genetic predisposition. We will discuss current diagnostic criteria, differential diagnoses, implications, and management of these parasomnias. Recent scientific developments in this area will be discussed, especially in reference to etiopathogenesis and treatment strategies of lesser-studied subtypes such as sexsomnia. The mainstay of treatment comprises alleviating the contributing factors and treating any comorbid sleep disorders that may curtail sleep duration and also increase abnormal arousal. Behavioral interventions can be beneficial, although sometimes less established pharmacotherapy is also utilized.</p>","PeriodicalId":49544,"journal":{"name":"Seminars in Neurology","volume":" ","pages":"358-367"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seminars in NeurologyPub Date : 2025-04-01Epub Date: 2025-02-06DOI: 10.1055/a-2534-3335
Shilpa B Reddy, Emma G Carter
{"title":"Dietary Therapies in Epilepsy.","authors":"Shilpa B Reddy, Emma G Carter","doi":"10.1055/a-2534-3335","DOIUrl":"10.1055/a-2534-3335","url":null,"abstract":"<p><p>Ketogenic diet therapies are an increasingly utilized treatment option for adult and pediatric patients with drug-resistant epilepsy. The two most common are the classic ketogenic diet, following a ratio of fat to combined protein and carbohydrates (typically 4:1), and the modified Atkins diet, limiting total carbohydrates to 10 to 30 g per day. Based on high-quality studies in pediatric patients, the classic ketogenic and modified Atkins diets show >50% reduction in seizure frequency in approximately 40 to 50% of patients. Although there are fewer overall and high-quality studies in adults, they show similar seizure efficacy rates, but notably high rates of noncompliance. In addition to improved seizure outcomes, ketogenic diet therapies have been associated with improved cognitive and quality of life measures. Ketogenic diet therapies are generally safe but require monitoring to ensure adequate growth and tolerance. The core of a ketogenic diet program is a well-trained multidisciplinary team, supported by operational and evidence-based protocols.</p>","PeriodicalId":49544,"journal":{"name":"Seminars in Neurology","volume":" ","pages":"221-231"},"PeriodicalIF":1.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seminars in NeurologyPub Date : 2025-04-01Epub Date: 2025-03-17DOI: 10.1055/a-2559-7520
Akshay Sharma, Demitre Serletis, Ajay Gupta
{"title":"Surgical: Resection/Destructive Procedures.","authors":"Akshay Sharma, Demitre Serletis, Ajay Gupta","doi":"10.1055/a-2559-7520","DOIUrl":"10.1055/a-2559-7520","url":null,"abstract":"<p><p>Surgical resection and ablation are powerful tools in the treatment of medically refractory epilepsy. In this study, we review a broad array of resective and ablative procedures available to the epilepsy surgeon to address surgical epileptic disease. Here, we aim to provide a brief overview of a very broad category of treatments to provide a better understanding of the breadth of treatments available to providers and patients.</p>","PeriodicalId":49544,"journal":{"name":"Seminars in Neurology","volume":" ","pages":"232-240"},"PeriodicalIF":1.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}