Epilepsia
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A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of epileptogenesis (the development of epilepsy) and ictogenesis (the propensity to generate spontaneous seizures) might predict the development of an epilepsy condition; identify the presence and severity of tissue capable of generating spontaneous seizures; measure progression after the condition is established; and determine pharmacoresistance. ⋯ The objectives of the biomarker subgroup for the London Workshop were to define approaches for identifying possible biomarkers for these purposes. Research to identify reliable biomarkers may also reveal underlying mechanisms that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compounds.
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Review
Epilepsy therapy development: technical and methodologic issues in studies with animal models.
The search for new treatments for seizures, epilepsies, and their comorbidities faces considerable challenges. This is due in part to gaps in our understanding of the etiology and pathophysiology of most forms of epilepsy. An additional challenge is the difficulty in predicting the efficacy, tolerability, and impact of potential new treatments on epilepsies and comorbidities in humans, using the available resources. ⋯ We further discuss the different expectations for studies aiming to meet regulatory requirements to obtain approval for clinical testing in humans. Implementation of the rigorous practices discussed in this report will require considerable investment in time, funds, and other research resources, which may create challenges for academic researchers seeking to contribute to epilepsy therapy discovery and development. We propose several infrastructure initiatives to overcome these barriers.
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A working group was created to address clinical "gaps to care" as well as opportunities for development of new treatment approaches for epilepsy. The working group primarily comprised clinicians, trialists, and pharmacologists. The group identified a need for better animal models for both efficacy and tolerability, and noted that animal models for potential disease-modifying or antiepileptogenic effect should mirror conditions in human trials. ⋯ The group identified common and rare epilepsy syndromes that could represent opportunities for clinical trials. They identified opportunities for antiepileptogenic (AEG) therapies in both adults and children, acknowledging that the presence of a biomarker would substantially improve the chances of a successful trial. However, the group acknowledged that disease-modifying therapies (given after the first seizure or after the development of epilepsy) would be easier to study than AEG therapies.
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Review Meta Analysis
Adverse events related to extraoperative invasive EEG monitoring with subdural grid electrodes: a systematic review and meta-analysis.
Implantation of subdural grids and invasive electroencephalography (EEG) monitoring is important to define the ictal-onset zone and eloquent cortex in selected patients with medically refractory epilepsy. The objective of this systematic review is to summarize data about adverse events related to this procedure. ⋯ Although providing critical information for patients with medically refractory epilepsy, subdural grids implantation and invasive EEG monitoring entails risks of infection, hemorrhage, and elevated intracranial pressure. The prevalence estimates, likely to be conservative due to selective reporting, are expected to be helpful in counseling patients.
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Neurocysticercosis (NCC) is the main risk factor for late-onset seizures in many Taenia solium endemic countries and is also increasingly recognized in high income countries, where it was once thought to have been eliminated. The course and outcome of NCC-associated seizures and epilepsy are poorly understood. Substrates underlying NCC-associated seizures and epilepsy are unknown. ⋯ The former are convincing cases of medically intractable epilepsy with good seizure control following hippocampal resection. In the remaining, it is unclear whether a dual pathology relationship exists between HS and the calcified cysticercus. Carefully planned, follow-up studies incorporating high-resolution and quantitative imaging are desirable in order to clarify the outcome, the structural basis of NCC-associated epilepsy, and also its association with HS.