ReviewPrecision medicine in women with epilepsy: The challenge, systematic review, and future direction
Section snippets
Introduction:
Epilepsy is one of the most prevalent neurologic conditions and an important cause of disability. It has been estimated to affect almost 70 million people worldwide. In the United States, 1.2% of the population has epilepsy as an active diagnosis, including over one million women of childbearing age [1]. Women with epilepsy (WWE) face specific challenges throughout their lifespan, such as special reproductive and general health concerns.
Recent biotechnological advances have led to a rapid
Women with epilepsy (WWE) and pregnancy outcomes
Over 90% of pregnancies in WWE proceed without any apparent complications [3]. However, WWE are considered at high risk in pregnancy due to increased maternal and fetal risks. They face particular challenges during their pregnancy, such as spontaneous abortion, antepartum hemorrhage, gestational hypertension, pre-eclampsia, breech position, induction of labor, cesarean section, and preterm birth [4]. Further, increased clearance of several anti-seizure medications (ASMs) during pregnancy can
Precision medicine approaches
This review section is tailored to neurologists and other clinicians who are less familiar with rapid developments in genomic medicine. From discovery of the double helix to the assembly of the human genome’s 3 billion nucleotides over the past decades, genomic medicine has undergone persistent rapid development. Recent advancements with next generation sequencing technique have improved the quality of sequencing while tremendously reducing the cost as well. Clinical practitioners have started
Systematic review of current pharmacogenomic approaches in treatment for WWE
Personalized treatment for WWE has long been advocated; it is complex and challenging, but the pharmacogenetic approach could be an important instrument. Here we provide an updated systematic review of studies that utilize pharmacogenetics to inform the management for WWE.
Biomarker identification for personalized treatment regimen
Prevalence of ASM use for pregnant women has increased from 15.7 per 1000 deliveries in 2001 to 21.9 per 1000 deliveries in 2007 in the United States, primarily driven by a 5-fold increase in the use of newer ASMs. This increase includes women beyond WWE, as ASMs are also commonly used in patients with psychiatric or pain disorders [34]. The general rule in clinical practice is to use an ASM with the least severe side-effect profile such as lamotrigine or levetiracetam, and to avoid valproate
Ethics of genetic testing
Precision medicine offers hope for patients, and in particular it has been applied fairly routinely in the field of oncology [76]. Hopefully, we will also expand the approach of precision medicine to our patients with epilepsy including WWE. Emerging genetic information and the availability of genetic testing in current clinical neurology practice, which even in the absence of active genetic modifications, can raise important ethical concerns [77]. A previous study has shown in apparently
Conclusion
In summary, in this era of medicine where epileptologists provide care using trial and failure to reduce the seizure burden, often at significant expense from continued seizures and from medication-related adverse effects and comorbidities of epilepsy such as adverse pregnancy and fetal outcomes, suboptimal bone health, as well as decreased quality of life; we envision a future in which precision medicine enables the emergence of new practice style shifting toward early detection, prediction,
Declaration of interest
Dr. Li reports no disclosures.
Dr. Zhang reports no disclosures.
Dr. Michael Snyder receives research support from National Institutes of Health (5UM1HG00944203, 5U24DK11234803, 5U54HG01042602, 5R01AT01023202, 1U2CCA233311-01, 1R25HG01085701).
Dr. Meador receives research support from the NIH NINDS, Sunovion Pharmaceuticals and Medtronic Navigation Inc, serves on the editorial boards of Neurology, Epilepsy & Behavior, Epilepsy & Behavior Case Reports, and Genes & Diseases, travel support from Eisai
Funding
Study supported by NIH NINDS, NICHD #2U01-NS038455 (Li, Meador).
Competing interests
The authors declare no competing interests.
Contributions
Yi Li: Study concept and design, literature review, data analysis, drafting and revising the manuscript.
Sai Zhang: Literature review, critical revision of manuscript for intellectual content.
Michael Snyder: Study concept and design, critical revision of manuscript for intellectual content.
Kimford Meador: Study concept and design, critical revision of manuscript for intellectual content.
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2023, The New Era of Precision Medicine: What it Means for Patients and the Future of HealthcareEffects of Maternal Use of Antiseizure Medications on Child Development
2022, Neurologic ClinicsCitation Excerpt :Recommendations to improve the situation have been made including a national reporting system for congenital malformations, routine meta-analyses of cohort studies to detect teratogenic signals, monitoring of ASM prescription practices for women, routine preclinical testing of all new ASMs for neurodevelopmental effects, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms for ASM-induced anatomic and behavioral teratogenesis.10 With such actions, future care in women requiring ASMs could be evidence-based and achieve precision medicine that focuses on early detection, prediction (eg, via susceptible genotype), and targeted therapies.84 ASMs pose anatomic and behavioral teratogenetic risks to the developing immature brain.
Maternal folic acid and multivitamin supplementation: International clinical evidence with considerations for the prevention of folate-sensitive birth defects
2021, Preventive Medicine ReportsCitation Excerpt :There has been no impact on the congenital anomaly prevalence with ‘high dose’ FA supplementation in epileptic pregnancy care (Harden, 2014; Keni et al., 2020; Baishya et al., 2020; Kashif et al., 2019; Harden et al., 2009; Harden et al., 2009; Morrow et al., 2009; Kjaer et al., 2008; Tomson et al., 2015; Herzog et al., 2017; Mahdavi et al., 2019) as the AEDs teratogenic mechanism may have no FA component or association (Harden et al., 2009; Harden et al., 2009; Morrow et al., 2009). High dose FA should no longer be recommended for congenital anomaly reduction for pregnant women with epilepsy (Stephen et al., 2019; Tomson et al., 2020; Li et al., 2021). Benefit from FA supplementation use in epileptic pregnancy cohorts has been associated with neonatal neurodevelopmental benefits (Meador et al., 2020).
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2024, Essentials of Neuropsychology: Integrating Eastern and Western PerspectivesAssisted reproductive technology outcomes and management considerations for people with epilepsy
2023, Current Opinion in Endocrinology, Diabetes and Obesity