Seminars in Neurology最新文献

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.

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.

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.

Advances in next-generation sequencing have allowed for genetic characterization of many epilepsies that previously had no known cause. Although having a precise diagnosis has been very helpful for management, counseling, and prognosis, until recently true precision medicine approaches that could have disease-modifying effects have been lacking. This review will highlight how preclinical animal models of Dravet syndrome have allowed some novel gene therapy approaches to be studied and further developed such that they are now entering into the clinics.

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.

Since the first antiseizure medication (ASM) was introduced in 1857, more than 30 medications have been approved by the United States Food and Drug Administration (FDA) for the treatment of epilepsy. However, limitations in efficacy and tolerability have led to one-third of patients suffering from uncontrolled seizures. Recent advances in genetics, disease modeling, high-throughput target-based and phenotype-based screening, study design, and identification of novel mechanisms of action or routes of delivery have resulted in more than 200 therapeutics currently under development in the epilepsy pipeline. This study discusses near-to-market drugs in advanced clinical development, with select drugs in earlier stages. Background regarding mechanisms, animal studies, pharmacokinetics, pharmacodynamics, efficacy, tolerability, and safety data are provided for each drug when available.

Developmental and epileptic encephalopathies (DEEs) are a group of rare, severe, early-onset epilepsies characterized by pharmacoresistance, marked electroencephalographic abnormalities, and delayed or regressive psychomotor development. DEEs are associated with poor long-term outcomes and increased mortality; however, early recognition and targeted treatment can impact neurodevelopmental outcomes and overall quality of life. Treatment with antiseizure medication is often challenging given drug resistance, chronic polypharmacy, and medication interactions. With advances in genetic testing and increased understanding of the neurobiological mechanisms of DEEs, the treatment approach is evolving and includes repurposed antiseizure medications and targeted therapies, as well as early surgical intervention in select patients. In addition to high seizure burden and neurodevelopmental delay, DEEs are associated with comorbidities affecting a range of body systems; these can include intellectual disability, psychiatric disorders, motor dysfunction, and respiratory and gastrointestinal problems. Over time, these comorbidities increase the complexity of management and have important implications on the disease burden and quality of life for both patients and their caregivers. Multidisciplinary care in DEEs is paramount. We summarize the current evidence on the management of specific DEEs, focusing on targeted therapies and optimizing outcomes.

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.