Volume 56, December 2025, 101236Author links open overlay panelDebopam SamantaShow moreAccess through your organization

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Access through your organizationSection snippetsDiagnostic progress and challenges

In this issue, the authors highlight the remarkable progress made in the diagnosis and understanding of LGS—from its original description by Lennox and Gastaut to the updated International League Against Epilepsy (ILAE) diagnostic criteria established in 2022.1,5,6 The revised criteria emphasize the presence of both slow spike–wave discharges (SSW) and generalized paroxysmal fast activity (GPFA) on EEG for diagnosis.1 Despite these advances, practical challenges remain in applying these

Therapeutic landscape and treatment challenges

Despite important progress in diagnostic criteria, the management of LGS remains highly challenging. Seizures are often resistant to therapy despite the availability of multiple antiseizure medications (ASMs). To date, eight ASMs have received specific U.S. Food and Drug Administration (FDA) approval for LGS: clonazepam, felbamate, lamotrigine, topiramate, rufinamide, clobazam, cannabidiol, and fenfluramine.9 In addition, several other ASMs—most notably valproate—are frequently used off-label

Beyond pharmacological approaches

Given the limited efficacy of pharmacological therapies in many individuals with LGS, several nonpharmacological interventions are routinely employed, including dietary therapies, neuromodulation, and resective or ablative surgery.13 In this issue, Fine et al. review the role of dietary interventions, while Karakas et al. provide a detailed overview of neuromodulation therapies—including vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS)—in LGS

Patient-centered outcomes

A major evolution in LGS research and clinical care has been the transition from a seizure-centric to a patient-centered approach, emphasizing functional outcomes and health-related quality of life (HRQoL). In this issue, Patel et al. examine HRQoL in individuals with LGS and their families, highlighting the complex interplay between seizures, comorbidities, and psychosocial burden. Erdemir et al. further explore comorbidities and co-occurring conditions that critically influence daily

Network-based understanding

A major advance in the understanding of LGS has been the application of neuroimaging and neurophysiological methods to conceptualize it as a secondary network epilepsy involving large-scale brain systems.30,31 Distinct interictal EEG patterns—such as GPFA, SSW, and generalized spike–wave (GSW)—appear to reflect activation or suppression of specific brain networks. GPFA, often associated with tonic seizures, corresponds to widespread activation across the frontal and parietal association

Future directions and remaining challenges

Despite recent advances, substantial challenges persist. Standardization of LGS treatment and dissemination of current research findings are needed to improve quality of care, which this special issue seeks to facilitate. The natural history of LGS also remains incompletely characterized.36 Prospective studies and the integration of large retrospective datasets will be essential to better understand LGS trajectories across the lifespan and to design clinical trials that address these dynamic

Conclusion

Amid rapid advances in neuroimaging biomarkers, refined diagnostic definitions, emerging treatments including precision therapies, and the implementation of standardized outcome measures, it is vital not to lose sight of the foundational aspects of patient care. Access to comprehensive healthcare for individuals with LGS remains challenging. Clinicians and advocates must continue to ensure that patients and families receive multidisciplinary support, including special education, sensory and

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