Epilepsia
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Review Meta Analysis
Identification of new epilepsy treatments: issues in preclinical methodology.
Preclinical research has facilitated the discovery of valuable drugs for the symptomatic treatment of epilepsy. Yet, despite these therapies, seizures are not adequately controlled in a third of all affected individuals, and comorbidities still impose a major burden on quality of life. The introduction of multiple new therapies into clinical use over the past two decades has done little to change this. ⋯ New therapies also need to address the special needs of certain subpopulations, that is, age- or gender-specific treatments. Preclinical development in these treatment areas is complex due to heterogeneity in presentation and etiology, and may need to be formulated with a specific seizure, epilepsy syndrome, or comorbidity in mind. The aim of this report is to provide a framework that will help define future guidelines that improve and standardize the design, reporting, and validation of data across preclinical antiepilepsy therapy development studies targeting drug-resistant seizures, epileptogenesis, and comorbidities.
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Review Meta Analysis
A systematic review and meta-analysis of heart rate variability in epilepsy and antiepileptic drugs.
Epilepsy is associated with near-fatal and fatal arrhythmias, and sudden unexpected death in epilepsy (SUDEP) is partly related to cardiac events. Dysfunction of the autonomous nervous system causes arrhythmias and, although previous studies have investigated the effects of epilepsy on the autonomic control of the heart, the results are still mixed regarding whether imbalance of sympathetic, vagal, or both systems is present in epilepsy, and also the importance of anticonvulsant treatment on the autonomic system. Therefore, we aimed to investigate epilepsy and its treatment impact on heart rate variability (HRV), assessed by sympathetic and parasympathetic activity expressed as low-frequency (LF) and high-frequency (HF) power spectrum, respectively. ⋯ We confirmed and extended the hypothesis of sympathovagal imbalance in epilepsy, as showed by lower HF, SDNN, and RMSSD values when compared to controls. In addition, there was a trend for higher LF values in patients receiving pharmacotherapy. As lower vagal (HF) and higher sympathetic (LF) tone are predictors of morbidity and mortality in cardiovascular samples, our findings highlight the importance of investigating autonomic function in patients with epilepsy in clinical practice. Assessing HRV might also be useful when planning therapeutic interventions, as some antiepileptic drugs can show hazardous effects in cardiac excitability, potentially leading to cardiac arrhythmia.
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Stereotactic radiosurgery, well established in the noninvasive treatment of focal lesions that are otherwise difficult to access through open surgery, is an emerging technology in the treatment of focal epileptic lesions. Recent studies suggest that seizures from hypothalamic hamartomas and mesial temporal lobe epilepsy remit at clinically significant rates with radiosurgery, but large variations among different studies have raised questions about appropriate treatment protocols and mechanisms. Proposed anticonvulsant mechanisms include neuromodulatory effects or ischemic necrosis of epileptic tissue. An ongoing trial that directly compares efficacy, morbidities, and cost of radiosurgery versus open surgery for mesial temporal lobe epilepsy is underway.
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Gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNETs) are low-grade brain tumors of glioneuronal origin that commonly present with seizures. Achieving seizure control in patients with glioneuronal tumors remains underappreciated, as tumor-related epilepsy significantly affects patients' quality-of-life. ⋯ These results suggest that early operative intervention and gross-total resection are critically important factors in achieving seizure-freedom, and thus improving quality-of-life, in patients with glioneuronal tumors causing epilepsy.
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The International League Against Epilepsy (ILAE) standardized classification and terminology for "epileptic seizures" of 1981 and "epilepsies and epileptic syndromes" of 1989 provide a fundamental framework for organizing and differentiating the epilepsies. However, a revision of these classifications is mandated by recent major technologic and scientific advances. Since 1997, the relevant ILAE Commissions have made significant efforts to achieve better and internationally uniform classifications as reflected in their reports of 2001, 2006, and 2010. ⋯ The ILAE Commission could benefit by asking experts in basic and clinical science to provide a concise statement in their field of expertise as, for example, what are focal, myoclonic, or absence seizures, and their subtypes, their manifestations, and their possible pathophysiology. Areas of certainties and uncertainties, agreements and disagreements should be identified and stated clearly, with documentation of the reasons for it. Probably this is the only way forward for a truly scientific, sound, and clinically meaningful organizational system for the epileptic seizures and the epilepsies.