Neuromodulation Strategies in Lennox-Gastaut Syndrome: Practical Clinical Guidance from the Pediatric Epilepsy Research Consortium

Debopam Samanta¹, Gewalin Aungaroon², Anthony L Fine³, Cemal Karakas⁴, Michelle Y Chiu⁵, Puneet Jain⁶, Syndi Seinfeld⁷, Juliet K Knowles⁸, Ismail S Mohamed⁹, Carl E Stafstrom¹⁰, Tracy Dixon-Salazar¹¹, Anup D Patel¹², Sonam Bhalla¹³, Cynthia Guadalupe Keator¹⁴, Jorge Vidaurre¹⁵, Aaron E L Warren¹⁶, Renée A Shellhaas¹⁷, M Scott Perry¹⁴

Affiliations

¹ Division of Child Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: dsamanta@uams.edu.
² Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
³ Division of Child and Adolescent Neurology, Department of Neurology, Mayo Clinic, Rochester, MN, USA.
⁴ Division of Pediatric Neurology, Department of Pediatrics, Norton Children's Hospital, University of Louisville, Louisville, KY 40202, USA.
⁵ Epilepsy Division, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Epilepsy Program, Division of Neurology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
⁷ Neuroscience Center, Joe DiMaggio Children's Hospital, Hollywood, FL, USA.
⁸ Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA.
⁹ Department of Pediatrics, University of Alabama, Birmingham, AL, USA.
¹⁰ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Lennox-Gastaut Syndrome Foundation, San Diego, CA, USA.
¹² Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA; The Center for Clinical Excellence, Nationwide Children's Hospital, Columbus, OH, USA.
¹³ Division of Child Neurology, Emory University/Children's Healthcare of Atlanta, USA.
¹⁴ Jane and John Justin Institute for Mind Health, Cook Children's Medical Center, Ft Worth, TX, USA.
¹⁵ Department of Pediatrics, Division of Pediatric Neurology, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.
¹⁶ Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
¹⁷ Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.

PMID: 39778379
DOI: 10.1016/j.eplepsyres.2024.107499

Review

Neuromodulation Strategies in Lennox-Gastaut Syndrome: Practical Clinical Guidance from the Pediatric Epilepsy Research Consortium

Debopam Samanta et al. Epilepsy Res. 2025 Feb.

. 2025 Feb:210:107499.

doi: 10.1016/j.eplepsyres.2024.107499. Epub 2025 Jan 2.

Authors

Affiliations

¹ Division of Child Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: dsamanta@uams.edu.
² Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
³ Division of Child and Adolescent Neurology, Department of Neurology, Mayo Clinic, Rochester, MN, USA.
⁴ Division of Pediatric Neurology, Department of Pediatrics, Norton Children's Hospital, University of Louisville, Louisville, KY 40202, USA.
⁵ Epilepsy Division, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Epilepsy Program, Division of Neurology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
⁷ Neuroscience Center, Joe DiMaggio Children's Hospital, Hollywood, FL, USA.
⁸ Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA.
⁹ Department of Pediatrics, University of Alabama, Birmingham, AL, USA.
¹⁰ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Lennox-Gastaut Syndrome Foundation, San Diego, CA, USA.
¹² Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA; The Center for Clinical Excellence, Nationwide Children's Hospital, Columbus, OH, USA.
¹³ Division of Child Neurology, Emory University/Children's Healthcare of Atlanta, USA.
¹⁴ Jane and John Justin Institute for Mind Health, Cook Children's Medical Center, Ft Worth, TX, USA.
¹⁵ Department of Pediatrics, Division of Pediatric Neurology, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.
¹⁶ Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
¹⁷ Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.

PMID: 39778379
DOI: 10.1016/j.eplepsyres.2024.107499

Abstract

Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, cognitive impairment, and distinctive electroencephalographic patterns. Neuromodulation techniques, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS), have emerged as important treatment options for patients with LGS who do not respond adequately to antiseizure medications. This review, developed with input from the Pediatric Epilepsy Research Consortium (PERC) LGS Special Interest Group, provides practical guidance for clinicians on the use of these neuromodulation approaches in patients with LGS. We discuss patient selection criteria, expected seizure and non-seizure outcomes, potential complications, and device management considerations for each technique. The review also covers initiation and titration strategies, ongoing care requirements, and emerging data on combining multiple neuromodulation modalities. While all three approaches can reduce seizure frequency in patients with LGS, with commonly reported responder rates ranging from 50 % to 60 %, their impacts on cognition, behavior and quality of life are more variable. Careful patient selection, individualized programming, and long-term follow-up are essential to optimize outcomes with neuromodulation in this challenging patient population. Further research is needed to identify optimal candidates, determine the ideal timing during patients' clinical course to consider neuromodulation, develop standardized outcome measures, and evaluate the comparative effectiveness and cost-effectiveness of different neuromodulation techniques for LGS.

Keywords: Deep Brain Stimulation (DBS); Lennox-Gastaut Syndrome (LGS); Neuromodulation; Responsive Neurostimulation (RNS); Seizure management; Vagus Nerve Stimulation (VNS).

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Neuromodulation Strategies in Lennox-Gastaut Syndrome: Practical Clinical Guidance from the Pediatric Epilepsy Research Consortium

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Neuromodulation Strategies in Lennox-Gastaut Syndrome: Practical Clinical Guidance from the Pediatric Epilepsy Research Consortium

Authors

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Abstract

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