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Management of Infantile Epilepsies
Comparative Effectiveness Review, No. 252
Investigators: Jonathan R. Treadwell, Ph.D., Mingche Wu, M.S., and Amy Y. Tsou, M.D., M.Sc.
Structured Abstract
Objectives:
Uncontrolled seizures in children 1 to 36 months old have serious short-term health risks and may be associated with substantial developmental, behavioral, and psychological impairments. We evaluated the effectiveness, comparative effectiveness, and harms of pharmacologic, dietary, surgical, neuromodulation, and gene therapy treatments for infantile epilepsies.
Data sources:
We searched Embase®, MEDLINE®, PubMed®, the Cochrane Library, and gray literature for studies published from January 1, 1999, to August 19, 2021.
Review methods:
Using standard Evidence-based Practice Center methods, we refined the scope and applied a priori inclusion criteria to the >10,000 articles identified. We ordered full text of any pediatric epilepsy articles to determine if they reported any data on those age 1 month to <36 months. We extracted key information from each included study, rated risk of bias, and rated the strength of evidence. We summarized the studies and outcomes narratively.
Results:
Forty-one studies (44 articles) met inclusion criteria. For pharmacotherapy, levetiracetam may cause seizure freedom in some patients (strength of evidence [SOE]: low), but data on other medications (topiramate, lamotrigine, phenytoin, vigabatrin, rufinamide, stiripentol) were insufficient to permit conclusions. Both ketogenic diet and the modified Atkins diet may reduce seizure frequency (SOE: low for both). In addition, the ketogenic diet may cause seizure freedom in some infants (SOE: low) and may be more likely than the modified Atkins diet to reduce seizure frequency (SOE: low). Both hemispherectomy/hemispherotomy and non-hemispheric surgical procedures may cause seizure freedom in some infants (SOE: low for both), but the precise proportion is too variable to estimate. For three medications (levetiracetam, topiramate, and lamotrigine), adverse effects may rarely be severe enough to warrant discontinuation (SOE: low). For topiramate, non-severe adverse effects include loss of appetite and upper respiratory tract infection (SOE: moderate). Harms of diets were sparsely reported. For surgical interventions, surgical mortality is rare for functional hemispherectomy/hemispherotomy and non-hemispheric procedures (SOE: low), but evidence was insufficient to permit quantitative estimates of mortality or morbidity risk. Hydrocephalus requiring shunt placement after multilobar, lobar, or focal resection is uncommon (SOE: low). No studies assessed neuromodulation or gene therapy.
Conclusions:
Levetiracetam, ketogenic diet, modified Atkins diet, and surgery all appear to be effective for some infants. However, the strength of the evidence is low for all of these modalities due to lack of control groups, low patient enrollment, and inconsistent reporting. Future studies should compare different pharmacologic treatments and compare pharmacotherapy with dietary therapy. Critical outcomes underrepresented in the literature include quality of life, sleep outcomes, and long-term development.
Contents
- Preface
- Acknowledgments
- Key Informants
- Technical Expert Panel
- Peer Reviewers
- Executive Summary
- Introduction
- Methods
- Results
- Results of Literature Searches
- Key Question 1. What are the effectiveness and comparative effectiveness of pharmacologic treatments for infantile epilepsies (infants age 1 month to <36 months)?
- Key Question 2. What are the effectiveness and comparative effectiveness of non-pharmacologic treatments for infantile epilepsies (e.g., dietary therapies, surgery, neuromodulation, gene therapy), including comparisons to other non-pharmacologic and/or pharmacologic therapies?
- Key Question 3. What are the harms or comparative harms of treatments for infantile epilepsies?
- Discussion
- References
- Abbreviations
- Appendixes
Suggested citation:
Treadwell JR, Wu M, Tsou AY. Management of Infantile Epilepsies. Comparative Effectiveness Review No. 252. (Prepared by the ECRI–Penn Medicine Evidence-based Practice Center under Contract No. 75Q80120D00002.) AHRQ Publication No. 22(23)-EHC004. Rockville, MD: Agency for Healthcare Research and Quality. PCORI Publication No. 2021-SR-01. October 2022. DOI: https://doi.org/110.23970/AHRQEPCCER252. Posted final reports are located on the Effective Health Care Program search page.
This report is based on research conducted by the ECRI–Penn Medicine Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 75Q80120D00002). The Patient-Centered Outcomes Research Institute® (PCORI®) funded the report (PCORI Publication No. 2021-SR-01). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ or PCORI. Therefore, no statement in this report should be construed as an official position of PCORI, AHRQ, or the U.S. Department of Health and Human Services.
None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.
The information in this report is intended to help healthcare decision makers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of healthcare services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.
This report is made available to the public under the terms of a licensing agreement between the author and the Agency for Healthcare Research and Quality. This report may be used and reprinted without permission except those copyrighted materials that are clearly noted in the report. Further reproduction of those copyrighted materials is prohibited without the express permission of copyright holders.
PCORI®, AHRQ, or U.S. Department of Health and Human Services endorsement of any derivative products that may be developed from this report, such as clinical practice guidelines, other quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied.
AHRQ appreciates appropriate acknowledgment and citation of its work. Suggested language for acknowledgment: This work was based on an evidence report, Management of Infantile Epilepsies, by the Evidence-based Practice Center Program at the Agency for Healthcare Research and Quality (AHRQ).
- NLM CatalogRelated NLM Catalog Entries
- Pharmacologic and Dietary Treatments for Epilepsies in Children Aged 1-36 Months: A Systematic Review.[Neurology. 2023]Pharmacologic and Dietary Treatments for Epilepsies in Children Aged 1-36 Months: A Systematic Review.Treadwell JR, Kessler SK, Wu M, Abend NS, Massey SL, Tsou AY. Neurology. 2023 Jan 3; 100(1):e16-e27. Epub 2022 Oct 21.
- Surgical Treatments for Epilepsies in Children Aged 1-36 Months: A Systematic Review.[Neurology. 2023]Surgical Treatments for Epilepsies in Children Aged 1-36 Months: A Systematic Review.Tsou AY, Kessler SK, Wu M, Abend NS, Massey SL, Treadwell JR. Neurology. 2023 Jan 3; 100(1):e1-e15. Epub 2022 Oct 21.
- Ketogenic diets for drug-resistant epilepsy.[Cochrane Database Syst Rev. 2020]Ketogenic diets for drug-resistant epilepsy.Martin-McGill KJ, Bresnahan R, Levy RG, Cooper PN. Cochrane Database Syst Rev. 2020 Jun 24; 6(6):CD001903. Epub 2020 Jun 24.
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