Epilepsia
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Review Comparative Study
Psychiatric outcomes of epilepsy surgery: a systematic review.
The objective of this systematic review was to identify: (1) prevalence and severity of psychiatric conditions before and after resective epilepsy surgery, (2) incidence of postsurgical psychiatric conditions, and (3) predictors of psychiatric status after surgery. ⋯ Overall, studies demonstrated either improvement in psychiatric outcomes postsurgery or no change. However, there is a need for more prospective, well-controlled studies to better delineate the prevalence and severity of psychiatric conditions occurring in the context of epilepsy surgery, and to identify specific predictors of psychiatric outcomes after epilepsy surgery.
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Review Meta Analysis
The adverse event profile of pregabalin: a systematic review and meta-analysis of randomized controlled trials.
Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available randomized controlled trials (RCTs) of a given AED to fully uncover its tolerability profile. We aimed at identifying treatment emergent adverse events (AEs) associated with pregabalin through a systematic review and meta-analysis of all available RCTs. We also assessed the association between serious AEs and pregabalin, and investigated whether pregabalin AEs display a dose-response relationship. ⋯ Individuals starting treatment with pregabalin are at increased risk for several AEs, particularly those affecting cognition/coordination. Pregabalin AEs appear according to a selective dose-response pattern, possibly reflecting the severity of dysfunction of distinct anatomic structures. These findings may aid clinicians in providing better patient management, and support the value of including in meta-analyses of AED tolerability profiles RCTs performed in different conditions.
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Editorial Review
Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma.
Despite the development of various new antiepileptic drugs (AEDs) since the early 1990s, the available evidence indicates that the efficacy and tolerability of drug treatment of epilepsy has not substantially improved. What are the reasons for this apparent failure of modern AED development to discover drugs with higher efficacy? One reason is certainly the fact that, with few exceptions, all AEDs have been discovered by the same conventional animal models, particularly the maximal electroshock seizure test (MES) in rodents, which served as a critical gatekeeper. These tests have led to useful new AEDs, but obviously did not help developing AEDs with higher efficacy in as yet AED-resistant patients. ⋯ The failure of AED development has led to increasing disappointment among clinicians, basic scientists, and industry and may halt any further improvement in the treatment of epilepsy unless we find ways out of this dilemma. Therefore, we need new concepts and fresh thinking about how to radically change and improve AED discovery and development. In this respect, the authors of this critical review will discuss several new ideas that may hopefully lead to more efficacious drug treatment of epilepsy in the future.
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Nonconvulsive status epilepticus (NCSE) in a comatose patient cannot be diagnosed without electroencephalography (EEG). In many advanced coma stages, the EEG exhibits continuous or periodic EEG abnormalities, but their causal role in coma remains unclear in many cases. To date there is no consensus on whether to treat NCSE in a comatose patient in order to improve the outcome or to retract from treatment, as these EEG patterns might reflect the end stages of a dying brain. ⋯ Hence coma-LED and coma-GED can be diagnosed with EEG only. Subtle or stuporous status epilepticus and epilepsia partialis continua-like symptoms in severe acute central nervous system (CNS) disorders represent the borderland in this biologic continuum between NCSE proper and comatose NCSE (coma-LED/GED). This pragmatic differentiation could act as a starting point to solve terminologic and factual confusion.
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Review Comparative Study
Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: From tuberous sclerosis to common acquired epilepsies.
Most current treatments for epilepsy are symptomatic therapies that suppress seizures but do not affect the underlying course or prognosis of epilepsy. The need for disease-modifying or "antiepileptogenic" treatments for epilepsy is widely recognized, but no such preventive therapies have yet been established for clinical use. A rational strategy for preventing epilepsy is to target primary signaling pathways that initially trigger the numerous downstream mechanisms mediating epileptogenesis. ⋯ In mouse models of TSC, mTOR inhibitors prevent the development of epilepsy and underlying brain abnormalities associated with epileptogenesis. Accumulating evidence suggests that mTOR also participates in epileptogenesis due to a variety of other causes, including focal cortical dysplasia and acquired brain injuries, such as in animal models following status epilepticus or traumatic brain injury. Therefore, mTOR inhibition may represent a potential antiepileptogenic therapy for diverse types of epilepsy, including both genetic and acquired epilepsies.