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Management and treatment of LGS are challenging, due to associated comorbidities and the treatment resistance of seizures. A panel of five epileptologists reconvened to provide updated guidance and treatment algorithms for LGS, incorporating recent advancements in antiseizure medications (ASMs) and understanding of DEEs. The resulting consensus document is based on current evidence from clinical trials and clinical practice and the panel's expert opinion, focusing on new ASMs with novel mechanisms of action, such as highly purified cannabidiol and fenfluramine. For a patient presenting with newly diagnosed LGS or suspected LGS, the recommended first\u2010line treatment continues to be valproate. If this is ineffective as monotherapy, adjunctive therapy with, firstly, lamotrigine and secondly, rufinamide, is recommended. If seizure control remains suboptimal, subsequent adjunctive ASM treatment options include (alphabetically) cannabidiol, clobazam, felbamate, fenfluramine, and topiramate, although evidence for these is more limited. Whenever possible, no more than two ASMs should be used together. Nonpharmacological treatment approaches should be used in conjunction with ASM therapy and include ketogenic diet therapies, vagus nerve stimulation, and corpus callosotomy. Patients with LGS that has evolved from another type of epilepsy who are not already being treated with valproate should be transitioned to valproate and then managed using the same algorithm as for newly diagnosed LGS. Older patients with established LGS should be reviewed at least annually by a suitably experienced neurologist. The revised guidance aims to improve seizure control and quality of life for patients with LGS through personalized, evidence\u2010based treatment strategies while addressing the challenges of accurate diagnosis and management in a rapidly evolving therapeutic landscape.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>Lennox\u2013Gastaut syndrome (LGS) is a severe type of epilepsy that usually starts in childhood but continues into adulthood. It is characterized by a variety of different types of seizures (abnormal electrical activity in the brain), which are difficult to treat and often cause people with the condition to fall and injure themselves. Most people with LGS have learning difficulties and need a lot of support, often in residential care. The authors are experts in treating people with LGS and this article provides up\u2010to\u2010date guidance and advice on how best to care for those with the condition.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.13075","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T22:38:08Z","timestamp":1734647888000},"page":"85-106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Refining management strategies for Lennox\u2013Gastaut syndrome: Updated algorithms and practical approaches"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3874-9749","authenticated-orcid":false,"given":"St\u00e9phane","family":"Auvin","sequence":"first","affiliation":[{"name":"INSERM NeuroDiderot Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Pediatric Neurology Department, CRMR Epilepsies Rares, ERN EpiCare APHP, Robert Debr\u00e9 University Hospital  Paris France"},{"name":"Institut Universitaire de France, (IUF)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7233-2771","authenticated-orcid":false,"given":"Alexis","family":"Arzimanoglou","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, Child Neurology Department, Hospital San Juan de D\u00e9u Coordinator of the ERN EpiCARE Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8738-5083","authenticated-orcid":false,"given":"Merc\u00e8","family":"Falip","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, Neurology Service Bellvitge University Hospital, L'Hospitalet de Llobregat  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6065-1476","authenticated-orcid":false,"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"},{"name":"IRCCS \u2018G. 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