PubMed · 14354124
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W H McCULLAGH. 1955. Epilepsy.. https://pubmed.ncbi.nlm.nih.gov/14354124/
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BACKGROUND: Everolimus, a mechanistic target of rapamycin (mTOR) inhibitor, is increasingly used in tuberous sclerosis complex (TSC)-associated epilepsy; however, long-term real-world outcomes and factors associated with favorable response remain unclear. This study aimed to evaluate the long-term seizure outcomes of adjunctive everolimus and explore clinical factors associated with treatment response. METHODS: We retrospectively recruited 21 patients with active TSC-associated epilepsy receiving adjunctive everolimus and assessed seizure outcomes during follow-up. Clinical characteristics were compared between responders and non-responders at 1 year after treatment initiation. RESULTS: Over a median treatment duration of 72 months, responder rates ranged from 53.8% to 64.7%, and seizure-free rates ranged from 33.3% to 41.2%. Responders had fewer involved organ systems at baseline (median 3 vs. 4, p = 0.020) and lower anti-seizure medication burden (median 2 vs. 4, p = 0.045). Younger age at treatment initiation showed a trend toward improved response. CONCLUSION: Adjunctive everolimus was associated with sustained long-term seizure reduction in this real-world cohort. In exploratory analyses, fewer involved organ systems and fewer baseline ASMs were associated with favorable treatment response. These findings require validation in larger prospective cohorts.
Phenotype definition consists of the use of epidemiologic, biological, molecular, or computational methods to systematically select features of a disorder that might result from distinct genetic influences. By carefully defining the target phenotype, or dividing the sample by phenotypic characteristics, we can hope to narrow the range of genes that influence risk for the trait in the study population, thereby increasing the likelihood of finding them. In this article, fundamental issues that arise in phenotyping in epilepsy and other disorders are reviewed, and factors complicating genotype-phenotype correlation are discussed. Methods of data collection, analysis, and interpretation are addressed, focusing on epidemiologic studies. With this foundation in place, the epilepsy subtypes and clinical features that appear to have a genetic basis are described, and the epidemiologic studies that have provided evidence for the heritability of these phenotypic characteristics, supporting their use in future genetic investigations, are reviewed. Finally, several molecular approaches to phenotype definition are discussed, in which the molecular defect, rather than the clinical phenotype, is used as a starting point.
2-[18F]Fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), ictal single-photon-emission computed tomography (ictal SPECT), and magnetoencephalography (MEG) represent three established functional imaging tests that offer unique information toward the localization of epilepsy for surgery evaluation and treatment. When these tests are combined with high-resolution magnetic fresonance imaging (MRI), epilepsy related structure and function disturbances may be localized with a degree of confidence and understanding not possible with electroencephalography (EEG), even ictal recordings with intracranial electrodes, the mainstay of tools for seizure localization. Use of these alternative tests allows an increased percentage of patients to be considered for surgical treatment. In particular, the additional information provided by these techniques has been demonstrated to help those patients with nonlocalizing MRI or extratemporal lobe epilepsy. Studies that address optimal use of these tests (alone and in combination) will build toward the next major advancement in the surgical treatment of epilepsy by allowing better patient selection, less risk, and better surgical outcomes. Ultimately, appropriate use of these tests, combined with more comprehensive functional brain mapping (e.g., with MEG or functional MRI), may lead to completely noninvasive epilepsy surgery evaluation.