Seminars in Neurology最新文献

Seizures are paroxysmal neurological events that are encountered by all medical specialties. Seizures are common, with 1 in 10 people experiencing a seizure at some point in their life. Furthermore, recurring unprovoked seizures are the hallmark of the condition of epilepsy, which encompasses a spectrum of syndromes that can occur across the lifespan. Although individual seizures may be brief occurrences, they are disruptive to an individual's activities of daily living (ADLs), increase the risk of physical injury, and adversely impact the mental well-being of those who experience them. Thus, in order to provide the best management, it falls into a clinician's domain to be informed of the types of seizures along with possible provoking factors and risks of recurrence, and when to make a diagnosis of epilepsy. Attention will be given to treatment of epilepsy with medications, characteristics that may impact management, and situations that require advanced specialty care.

The relationship between sex hormones and epilepsy involves intricate interactions that influence seizure susceptibility, reproductive health, and treatment approaches. Estrogen generally exhibits proconvulsant effects, while progesterone and its metabolite allopregnanolone have anticonvulsant properties. Variability in hormone levels during the menstrual cycle can exacerbate seizures, a phenomenon known as catamenial epilepsy. Effective management often requires a tailored combination of antiseizure medications (ASMs) and hormonal therapies. Women and others of childbearing potential face unique challenges, including higher rates of menstrual dysfunction, potential exacerbation of seizures during pregnancy, and increased risks associated with hormonal contraception and menopause. Careful ASM selection is critical to ensure maternal and fetal safety, with lamotrigine, levetiracetam, and oxcarbazepine being preferred options. Postpartum ASM adjustments and breastfeeding considerations are also essential for optimizing outcomes. Emerging research highlights the impact of hormonal interactions in transgender individuals undergoing gender-affirming therapies. For transwomen, estrogen could heighten seizure risk. Close monitoring and collaboration between health care providers are crucial for personalized care. The complex interplay between hormones and epilepsy underscores the need for ongoing research and individualized approaches to optimize seizure control and address the unique reproductive health needs of people with epilepsy.

The incidence of epilepsy is highest at the extremes of age. Drug resistance is present in approximately one-third of people with epilepsy but occurs at higher than average rates in children with seizure onset before age 3 years, owing to a variety of etiologies unique to this age group. Epilepsy surgery is an effective therapeutic option for drug-resistant epilepsy but is vastly underutilized. Epilepsy surgery in children under age 3 comes with distinct clinical challenges related to brain anatomy, evolving developmental maturation, and limitations of evaluation and surgical strategies. However, epilepsy surgery can lead to seizure freedom or significant seizure reduction in this age group. Early seizure control may have a significant positive impact on long-term cognitive development, making urgency of surgical referral of immense importance. This review highlights available evidence on the safety and efficacy of epilepsy surgery in early-life epilepsy, identifying barriers to surgical therapy, describing utilization of available evaluation and surgical strategies, and examining risks and benefits of earlier surgical consideration in this vulnerable population.

While pediatric epilepsy shares some features with adult epilepsy, the growing and developing brain during childhood is associated with differences in epilepsy etiologies, syndromes, comorbidities, management, and outcomes. We must also consider the long-term effects of epilepsy and treatments. This section highlights unique considerations for pediatric epilepsy. These include pediatric onset electroclinical syndromes that commonly resolve prior to adulthood, treatment duration of self-limited pediatric epilepsy syndromes, pediatric-onset epilepsy with etiology-specific treatment, and therapies used more commonly in the pediatric population. In addition, pediatric-onset epilepsy is associated with a higher risk for developmental, psychiatric, and behavioral comorbidities in a bidirectional fashion. Family dynamics are affected by a child with epilepsy, and transitioning to the adult clinic is a particular challenge for this population. Finally, there are special issues that occur in pediatric epilepsy, including the lack of pediatric FDA approvals for newly available therapies and the need for sedation for investigations.

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.

Although electricity has been used in medicine for thousands of years, bioelectronic medicine for treating epilepsy has become increasingly common in recent years. Invasive neurostimulation centers primarily around three approaches: vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS). These approaches differ by target (e.g., cranial nerve, cortex, or thalamus) and stimulation parameters (e.g., triggered stimulation or continuous stimulation). Although typically noncurative, these approaches can dramatically reduce the seizure burden and offer patients new treatment options. There remains much to be understood about optimal targets and individualized stimulation protocols. Objective markers of seizure burden and biomarkers that quickly quantify neural excitability are still needed. In the future, bioelectronic medicine could become a curative approach that remodels neural networks to reduce pathological activity.

Polyneuropathies are common, with the incidence increasing with older age. The causes of polyneuropathies are diverse and numerous, and it can be challenging for clinicians to determine the etiology of a particular patient's neuropathy. In this article, we systematically detail a practical approach to polyneuropathies, beginning with the most important aspects of the workup, the history and physical. We then discuss the limited diagnostic approach required for patients who present with a distal symmetric polyneuropathy and the more comprehensive approach for patients who present with other neuropathy subtypes.

Immune-mediated neuropathies encompass a range of neurological disorders, including chronic inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome, multifocal motor neuropathy, autoimmune autonomic neuropathies, and paranodal nodopathies. Recognizing clinical patterns is key to narrowing the broad range of differential diagnoses in immune-mediated neuropathies. Electrodiagnostic testing is a useful tool to support the diagnosis of immune-mediated neuropathies. Our understanding of autoimmune demyelinating neuropathies is rapidly advancing, particularly with the discovery of nodal and paranodal antibodies. Recent advances in neuropathy treatment include the utilization of neonatal Fc receptors to reduce antibody recycling, and the development of complement inhibitors to reduce inflammatory damage, offering promising new therapeutic avenues. Timely identification of immune-mediated neuropathies is imperative as delay in diagnosis and treatment may lead to irreversible disability.

This review explores diverse infectious etiologies of peripheral nervous system (PNS) dysfunction, spanning sensory and motor neurons, nerves, and associated structures. Progress in viral and bacterial infections reveals multifaceted mechanisms underlying neuropathies, including viral neurotoxicity and immune-mediated responses. Latest diagnostic advances facilitate early PNS complication detection, with ongoing research offering promising treatment avenues. Emerging pathogens like severe acute respiratory syndrome coronavirus 2, Zika virus, and EV-D68 highlight the evolving infectious neuropathy paradigm. Recognizing characteristic patterns and integrating clinical factors are pivotal for precise diagnosis and tailored intervention. Challenges persist in assessment and management due to varied pathogenic mechanisms. Advancements in understanding pathogenesis have improved targeted therapies, yet gaps remain in effective treatments. Ongoing research is crucial for optimizing approaches and improving patient outcomes.