Patrick Kwan

Objective Lennox‐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 a real‐world setting. Methods We applied ILAE diagnostic criteria to a cohort of patients diagnosed with LGS by epileptologists following inpatient video‐EEG monitoring (VEM) at tertiary comprehensive epilepsy centers between 1995 and 2015. We also assessed mortality in this cohort. Results Sixty 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 the 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%), ≤2.5 Hz 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. Significance Up 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 the 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. Plain Language Summary More than half of patients diagnosed with Lennox‐Gastaut Syndrome (LGS) at three Australian epilepsy monitoring units between 1995 and 2015 did not meet the recently devised International League Against Epilepsy (ILAE) diagnostic criteria for LGS. Mortality was equally high in those who did and did not meet the ILAE diagnostic criteria, and seizure‐related injury was common. The ILAE diagnostic criteria will guide accurate diagnosis, management, prognostication, and research in patients with LGS, however may be limited in their practical application to patients with a longer duration of epilepsy, or to those for whom detailed assessment is difficult.

Objective Differentiating status epilepticus (SE) from prolonged psychogenic nonepileptic seizures (pPNES) can be difficult clinically. We aimed to define the utility of peripheral cell counts, cell ratios, and lactate levels in distinguishing SE from pPNES. Methods Retrospective two‐center study investigating the sensitivity and specificity of acute (≤12 h of event offset) peripheral cell counts, cell ratios (neutrophil–lymphocyte ratio, neutrophil–monocyte ratio, monocyte–lymphocyte ratio, platelet–lymphocyte ratio, systemic immune‐inflammatory index [SII], systemic inflammatory response index [SIRI]), and lactate levels in differentiating SE from pPNES. Patients were identified from two tertiary hospitals, with one forming the development cohort and the other the validation cohort. Using generalized additive models to generate biomarker vs time curves, optimal blood collection times were defined for set parameters. Three diagnostic scores combining neutrophil count, SII, or SIRI with lactate levels were developed and validated in separate cohorts. Results For the development cohort, 1262 seizure‐like events were reviewed and 79 SE and 44 pPNES events were included. For the validation cohort, 241 events were reviewed and 20 SE and 11 pPNES events were included. Individually, the biomarkers generally had low sensitivity and reasonable specificity for differentiating SE from pPNES, with the neutrophil count, SIRI, and SII performing best with sensitivities of 0.65–0.84, specificities of 0.64–0.89, and ROC AUCs of 0.78–0.79. Lactate levels peaked at 60 min, while cell counts and ratios peaked after 240 min. Combining early peaking lactate levels and later peaking neutrophil count, SIRI or SII resulted in three scores that improved predictive potential with sensitivities of between 0.75 and 0.79, specificities between 0.93 and 1.00, and ROC AUCs of 0.89–0.91. Significance Lactate levels peak early post‐SE, whereas cell counts and ratios do so later. The differing post‐event time profiles of lactate levels vs neutrophil count, SIRI, and SII allow incorporation into three separate scores which can assist in differentiating SE from pPNES.