Cenobamate in refractory epilepsy: Overview of treatment options and practical considerations.

Management of drug resistant epilepsy (DRE) represents a challenge to the treating clinician. This manuscript addresses DRE and provides an overview of treatment options, medical, surgical, and dietary. It addresses treatment strategies in polytherapy, then focuses on the role cenobamate (CNB) may play in reducing the burden of DRE while providing practical advice for its introduction. CNB is a recently approved, third generation, anti-seizure medication (ASM), a tetrazole-derived carbamate, thought to have a dual mechanism of action, through its effect on sodium channels as well as on GABAA receptors at a non-benzodiazepine site. CNB, having a long half-life, is an effective add-on ASM in refractory focal epilepsy with a higher response rate and a higher seizure-freedom rate than is usually seen in regulatory clinical trials. Experience post-licensing, though still limited, supports the findings of clinical trials and is encouraging. Its spectrum of action in relation to generalized epilepsies and seizures remains to be established, and there are no data on its efficacy in monotherapy. At the time of writing, CNB has been prescribed for some 50 000 individuals with DRE and focal epilepsy. A larger number is needed to fully establish its safety profile. It should at all times be introduced slowly to minimize the risk of serious allergic drug reactions. It has clinically meaningful interactions which must be anticipated and managed to maximize tolerability and likelihood of successful treatment. Despite the above, it may well prove to be of major benefit in the treatment of many patients with drug resistant epilepsy.

Treatment of postsurgical psychiatric complications.

We describe the physical, psychological, and social complications and adaptation demands after epilepsy surgery and the risks of the development of psychiatric disorders when adequate stress processing fails. Practical strategies that can be followed in the prevention and treatment of postsurgical psychiatric complications are reviewed. The postoperative period is divided in three phases: (1) the early postoperative phase of stress processing until discharge from hospital; (2) the coping phase during the first months after discharge; and (3) the reorientation phase. The early postoperative course is often dominated by physical problems that hamper success in convalescence. They may initiate early psychiatric disturbances especially in patients with preoperative psychiatric comorbidity. The second phase after discharge from hospital is the typical time in which various psychiatric disorders may develop (either de novo or exacerbations of known disorders). At this time it is mandatory to keep in contact with patients, to start psychiatric treatments if necessary, and to assess for suicidal risk. The course of the third phase of reorientation depends on seizure outcome and on psychiatric state. Seizure-free persons without psychiatric comorbidities start to forget their epilepsy; those with less successful outcome conditions may need further support, especially for vocational integration. Epilepsy surgery brings about an overall strong improvement of psychiatric morbidity and quality of patients' life. Nevertheless, the first postoperative year is a fragile period that includes multiple physical, psychological, and social adaptation tasks. Patients with a history of psychiatric disorders are at a special risk of failing to cope with those health-related demands, but also for nonpsychiatric patients the months after epilepsy surgery are often stressful and exhausting. Professional help must be available during the postoperative coping time.

International consensus clinical practice statements for the treatment of neuropsychiatric conditions associated with epilepsy.

In order to address the major impact on quality of life and epilepsy management caused by associated neuropsychiatric conditions, an international consensus group of epileptologists met with the aim of developing clear evidence-based and practice-based statements to provide guidance on the management of these conditions. Using a Delphi process, this group prioritized a list of key management areas. These included: depression, anxiety, psychotic disorders, nonepileptic seizures, cognitive dysfunction, antiepileptic drug (AED)-related neurobehavioral disorders, suicidality, disorders in children and adolescents, disorders in children with intellectual disability, and epilepsy surgery. Clinical practice statements were developed for each area and consensus reached among members of the group. The assessment and management of these conditions needs to combine knowledge of psychiatric disorders, knowledge of the impact of epilepsy and its treatment on psychopathology, and an ability to deliver care within epilepsy services. The aim of these statements is to provide guidance on quality care for people with epilepsy that have a range of neuropsychiatric disorders.

Epilepsy treatment as a predeterminant of psychosocial ill health.

Epilepsy is a chronic disorder with complex effects on social, vocational, physical, and psychological well-being. Patient-oriented research has demonstrated that recurrent seizures have a strong adverse effect on health-related quality of life, but also that seizure rate in persons with pharmacoresistant epilepsy has only a modest correlation with quality of life. Although treatment side effects have received limited attention in epilepsy research, available evidence indicates that adverse medication effects may explain more variance in quality of life than any other clinical variable in persons with pharmacoresistant epilepsy. Furthermore, systematic screening for adverse effects has been shown to be associated with significant reduction in subjective toxicity and improvement in quality of life. There has been only limited research on the relative contribution of specific adverse effects to impaired health-related quality of life. The relative importance of reduction of medication burden after resective epilepsy surgery or vagal nerve stimulation has similarly received sparse attention. Existing deficiencies in the available published research present challenges and opportunities to perform further investigations to define and improve best clinical practices in epilepsy care.

A multicenter study of the Ambu laryngeal mask in nonparalyzed, anesthetized patients.

We designed this multicenter trial to evaluate the performance and safety of the Ambu laryngeal mask, a new disposable supraglottic airway device, in patients scheduled for elective surgery. One-hundred-eighteen nonparalyzed, anesthetized patients (ASA physical status I-II, age, 18-65 yr, body mass index, 18-30 kg/m(-2)) receiving total IV anesthesia were included in this study. After device insertion, fiberoptic position and oropharyngeal leak pressure were determined at an intracuff pressure of 60 cm H2O. Ease of ventilation was determined by controlling ventilation at 6 mL/kg tidal volume. Any complications were noted and recorded. Device placement was successful in all patients on the first or second attempt (92.4% or 7.6%, respectively) with an insertion time (removal of face mask until first tidal volume) of 44.9 +/- 37.91 s. Adequate ventilation was achieved in all patients and the vocal cords could be visualized by fiberoptic endoscopy in 91.5% of patients. Oropharyngeal leak pressures were 24.1 +/- 5.44 cm H2O. Blood was detected on the device in 8.5% of patients. Complications and patient complaints were minor and quickly resolved. The Ambu laryngeal mask is easy and quick to insert and provides a safe and efficient seal during positive pressure ventilation in nonparalyzed patients scheduled for elective surgery.

Depression and mania in patients with epilepsy.

Depression has a major impact on quality of life in patients with epilepsy and is also the main risk factor for the increased suicide rate in epilepsy. The frequency of depressive disorders depends on the severity of epilepsy and the localization of the epileptogenic focus, with a prevalence of