The refractory epilepsy screening tool for Lennox–Gastaut syndrome (REST-LGS)

ObjectiveLennox‐Gastaut syndrome (LGS) is an archetypal developmental and epileptic encephalopathy, for which novel treatments are emerging. Diagnostic criteria for LGS have recently been defined by the International League Against Epilepsy (ILAE). We aimed to apply these criteria in the real‐world setting.MethodsWe applied ILAE diagnostic criteria to a cohort of patients diagnosed with LGS by epileptologists following inpatient video‐EEG monitoring (VEM) at tertiary comprehensive epilepsy centres between 1995 and 2015. We also assessed mortality in this cohort.ResultsSixty patients diagnosed with LGS and had complete records available for review were Identified. Among them, 29 (48%) patients met ILAE diagnostic criteria for LGS (ILAE‐DC group). Thirty‐one did not meet criteria (non‐ILAE‐DC) due to absence of documented tonic seizures (n=7), EEG features (n=12), or both tonic seizures and EEG features (n=10), intellectual disability (n=1), or drug resistance (n=1). The ILAE‐DC group had a shorter duration of epilepsy at VEM than the non‐ILAE‐DC group (median = 12.0 years Vs 23.7 years, respectively; p=0.015). The proportions of patients with multiple seizure types (100% vs. 96.7%), ≤2.5Hz slow spike‐and‐wave EEG activity (100% vs. 90%), seizure‐related injuries (27.6% vs 25.8%), and mortality (standardized mortality ratio 4.60 vs. 5.12) were similar between the groups.SignificanceUp to 52% of patients diagnosed with LGS following VEM may not meet recently accepted ILAE criteria for LGS diagnosis. This may reflect both the limitations of retrospective medical record review and a historical tendency of applying the LGS diagnosis to a broad spectrum of severe, early‐onset drug‐resistant epilepsies with drop attacks. The ILAE criteria allow delineation of LGS based on distinct electroclinical features, potentiating accurate diagnosis, prognostication, and management formulation. Nonetheless, mortality outcomes between those who did and did not meet ILAE diagnostic criteria for LGS were similarly poor, and both groups suffered high rates of seizure‐related injury.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Applying the ILAE diagnostic criteria for Lennox‐Gastaut syndrome in the real‐world setting: A multicenter retrospective cohort study

Nightscales,

Chen,

Barnard

et al. 2024

“…The REST-LGS was designed using the Modified Delphi Consensus approach, a rigorous method in which available scientific evidence and collective judgment of a group of experts (including epileptologists, advanced practice nurses trained in epilepsy, neurology residents, and scientists) were combined to develop the screening tool. 13 The REST-LGS consists of 8 criteria - answer for all 4 major criteria is considered "Definite LGS". 13 The majority of patients with confirmed LGS in the original REST-LGS validation study exhibited 3 major criteria and 2 to 3 minor criteria, suggesting that meeting these thresholds would be indicative of LGS.…”

Section: Rest-lgs Questionnairementioning

confidence: 99%

“…13 The REST-LGS consists of 8 criteria - answer for all 4 major criteria is considered "Definite LGS". 13 The majority of patients with confirmed LGS in the original REST-LGS validation study exhibited 3 major criteria and 2 to 3 minor criteria, suggesting that meeting these thresholds would be indicative of LGS.…”

Section: Rest-lgs Questionnairementioning

confidence: 99%

“…Second, details of patients' medical histories may be lost during transfer of pediatric testing results to adult health care providers 11 . Third, patients may no longer tolerate EEG testing 12,13 . Finally, comorbid conditions, such as behavioral difficulties, cognitive impairment, and sleep disturbances, can develop in adolescence and adulthood, further complicating diagnosis and delaying treatment 11,14 .…”

Section: Introductionmentioning

confidence: 99%

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Real‐world use of the updated refractory epilepsy screening tool for Lennox–Gastaut syndrome

Wolf,

Boyce,

Peña

et al. 2024

Self Cite

ObjectiveTo evaluate the Refractory Epilepsy Screening Tool for Lennox–Gastaut Syndrome (REST‐LGS) for real‐world identification of LGS in adults and to develop a scoring system for the tool.MethodsA retrospective chart review of adults with drug resistant epilepsy (DRE) and intellectual development disorder (IDD) was conducted by 2 primary care providers blinded to diagnosis. The REST‐LGS was designed via the Modified Delphi Consensus and was previously validated. This tool consists of 8 criteria (4 major, 4 minor) considered indicative of LGS. To account for missing data in the earlier validation study and to evaluate applicability in a real‐world setting, the REST‐LGS was refined to include a scoring system in which major criteria were more heavily weighted than minor criteria, producing categories of “likely” (>11 points), “possible” (8–11 points), and “unlikely” (<8 points) LGS. Statistical analyses were descriptive.ResultsOf the 100 patients included in the analysis, data for slow spike–waves in electroencephalography and seizure onset age – both major REST‐LGS criteria – were missing for 46% and 42% of patients, respectively. The majority of patients met 4 of the 8 REST‐LGS criteria (cognitive impairment since childhood, 71%; persistent seizures despite a trial of ≥2 antiseizure medications, 65%; seizure onset before the age of 12 years, 57%; ≥2 seizure types, 56%). All 4 major criteria were met in 22 patients (22%). The percentages of patients considered “likely,” “possible,” or “unlikely” to have LGS were 26%, 30%, and 44%, respectively. Of the 74 patients without a previous LGS diagnosis, 42 (57%) were identified as “possible” or “likely” to have LGS using REST‐LGS.SignificanceIn this analysis, the validated REST‐LGS was evaluated in a real‐world setting. The majority of previously undiagnosed patients were identified via REST‐LGS as “possible” or “likely” to have LGS. Extensive missing data highlights challenges of LGS diagnosis in adults.Plain Language SummaryThere is a need to identify adult patients with Lennox–Gastaut syndrome (LGS) so they can receive appropriate treatment. The Refractory Epilepsy Screening Tool for LGS (REST‐LGS) questionnaire was designed by experts to identify whether patients with seizures that are not controlled by medications may have LGS. In this study, 2 physicians completed the REST‐LGS using charts for 100 patients who experience seizures not controlled by medications. Of the patients who were previously diagnosed as not having LGS, the majority were “likely” or “possible” to have LGS based on the REST‐LGS; therefore, the REST‐LGS can identify patients for further evaluation.

Consensus panel recommendations for the optimization of EPIDIOLEX® treatment for seizures associated with Lennox–Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex

Wechsler,

Burdette,

Gidal

et al. 2024

Following the approval of Epidiolex® (cannabidiol; CBD) for the treatment of seizures associated with Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC), healthcare professionals (HCPs) have had substantial experience in treating patients with Epidiolex. However, confusion still remains among HCPs, caregivers, and patients regarding dosing, drug interactions, safety monitoring, and differentiation between Epidiolex and nonapproved CBD products. To establish consensus recommendations for Epidiolex treatment optimization in LGS, DS, and TSC, a panel of seven HCPs with expertise in epilepsy was convened. Panelists participated in a premeeting survey based on a literature review of Epidiolex for the treatment of LGS, DS, and TSC, and survey responses were compiled for discussion. A modified Delphi method was used to assess agreement among panelists regarding recommendation statements following two rounds of discussion. Panelists identified two broad themes – overcoming barriers to initiation and optimization of treatment for seizures associated with LGS, DS, and TSC – for consensus guidelines. Accurate identification of patients with these rare epilepsies is critical for optimization of Epidiolex treatment. Providers should differentiate Epidiolex from nonapproved CBD products and set expectations for the therapeutic effect and safety/tolerability of Epidiolex. Initial target dose and titration rate should be individualized by baseline variables, prior response to antiseizure medications, and therapeutic goals. Awareness of strategies to manage adverse events and concomitant medications, including drug–drug interactions, is critical. Tracking response to the maximum tolerated dose is an important measure of effectiveness. These consensus recommendations provide real‐world experience from neurology HCPs with experience in prescribing Epidiolex and can inform optimal use of Epidiolex for the treatment of seizures associated with LGS, DS, and TSC.Plain language summaryEpidiolex® (cannabidiol) is approved for treating seizures in Lennox–Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. Although healthcare professionals have experience in treating patients with Epidiolex, there is a need for better understanding of dosing, drug interactions, and safety of this drug. Therefore, a group of epilepsy experts developed guidelines for best practices in Epidiolex treatment. Two main areas were identified: overcoming barriers to starting Epidiolex and considerations related to Epidiolex dosing. Within these areas, topics, including correct disease identification, managing adverse events, and determining individualized dose, were discussed. These guidelines provide real‐world experience to inform optimal Epidiolex use.