Seminars in Neurology最新文献

The term "funds flow" refers to the financial relationships between the schools or colleges of medicine and its parent university, the hospital/health system, and clinical departments. Funds flow arrangements vary greatly among organizations based on the relationships between these entities, their financial status, levels of extramural research support, and size of endowments and philanthropic activities. We review four general funds flow models: the "Make Whole" Model, the "Pay for Production" Model, the "Value-Based" Model, and the "Contribution Margin" Model. We also discuss issues that can affect how these models operate and the reasons they differ depending on organizational structures and financial postures.

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.

Autoimmune-associated seizures and epilepsy are increasingly recognized in clinical practice and can arise in the setting of acute encephalitis but in some cases may present with chronic focal epilepsy. These conditions are usually resistant to antiseizure therapy but may respond definitively to timely immunotherapy. Early diagnosis and treatment are critical to minimize neural injury and optimize outcomes.Treatment is guided by consensus opinion because definitive trials are currently lacking. The initial management approach usually involves first-line agents such as corticosteroids, intravenous immunoglobulin (IVIg), or plasma exchange, with second-line agents like rituximab or cyclophosphamide. Maintenance therapy is considered to prevent relapses, which occur in up to 35% of patients. Relapse management requires careful differentiation from postencephalitic epilepsy, which in the absence of active inflammation does not respond to immunotherapy.This review discusses treatment strategies for autoimmune-associated seizure disorders, including acute symptomatic seizures and epilepsy. We discuss expected outcomes on the basis of the underlying pathogenesis including cases mediated by autoantibodies targeting specific neuronal surface/synaptic antigens, and intracellular epitopes, and for cases lacking defined biomarkers. Specific approaches are outlined for disorders such as anti-LGI1, anti-NMDAR, anti-GABA-BR, and anti-GAD65 encephalitides, emphasizing tailored immunotherapy based on pathophysiology and clinical context.

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.

Disconnection procedures in epilepsy surgery have become an important tool for the management of multifocal drug-resistant epilepsy. In this chapter, we will review their indications, describe the technical procedures, and review outcome data in the literature. Among the curative approaches, anterior quadrant disconnection, posterior quadrant (PQ) disconnection, and functional hemispherectomy can be performed for patients whose epileptic focus resides in one hemisphere or one quadrant. Seizure freedom rates from these procedures range from 50 to 81% for anterior quadrant disconnections, 50 to 92% for PQ disconnections, and 43 to 93% for hemispherectomy. Although typically performed in the pediatric population, data suggest that carefully selected adult patients could also benefit from a disconnection procedure. Of the palliative approaches, corpus callosotomy has been shown to be effective for drop attacks, resulting in significant improvement in seizure frequency, severity, and quality of life. Minimally invasive alternatives to standard open corpus callosotomies with laser interstitial thermal therapy (LITT) have been proposed. Overall, surgical disconnection procedures are an effective way of treating multifocal epilepsy, with good outcomes that can improve the quality of life for these patients.

Circadian rhythms (CRs) are entrainable endogenous rhythms that respond to external stimuli and regulate physiological functions. The suprachiasmatic nucleus (SCN) in the hypothalamus is the mammalian master clock that synchronizes all other tissue-specific peripheral clocks, primarily through gamma-aminobutyric acid (GABA) and vasoactive intestinal polypeptide (VIP). The SCN follows Earth's 24-hour cycle by light entrainment through the retinohypothalamic tract. At the cellular level, the core clock genes CLOCK, BMAL1, PER1-PER3, CRY1, and CRY2 regulate CRs in a negative feedback loop. The circadian disruption of the sleep-wake cycle manifests in at least six distinct clinical conditions. These are the circadian rhythm sleep-wake disorders (CRSWDs). Their diagnosis is made by history, sleep diaries, and actigraphy. Treatment involves a combination of timed light exposure, melatonin/melatonin agonists, and behavioral interventions. In addition, CR disturbances and subsequent misalignment can increase the risk of a variety of illnesses. These include infertility and menstrual irregularities as well as diabetes, obesity, fatty liver disease, and other metabolic syndromes. In addition, a disruption in the gut microbiome creates a proinflammatory environment. CR disturbances increase the risk for mood disorders, hence the utility of light-based therapies in depression. People with neurodegenerative disorders demonstrate significant disturbances in their CRs, and in their sleep-wake cycles. Circadian realignment therapies can also help decrease the symptomatic burden of these disorders. Certain epilepsy syndromes, such as juvenile myoclonic epilepsy (JME), have a circadian pattern of seizures. Circadian disturbances in epilepsy can be both the consequence and cause for breakthrough seizures. The immune system has its own CR. Disturbances in these due to shift work, for instance, can increase the risk of infections. CR disturbances can also increase the risk of cancer by impacting DNA repair, apoptosis, immune surveillance, and cell cycle regulation. Moreover, the timing of chemotherapeutic agents has been shown to increase their therapeutic impact in certain cancers.