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Corticosteroids are commonly used to treat refractory epilepsy in children, but the heterogeneity of the population and lack of standardized outcome measures have limited understanding of their effectiveness. We conducted a single-center study of corticosteroids for epileptic encephalopathy to (a) identify domains for measurement and estimate potential effect sizes, (b) characterize heterogeneity, and (c) identify outcomes that may need better tools for measurement. In this retrospective single-center cohort study, children with epileptic encephalopathy (excluding infantile spasms) were treated with a standardized course of oral dexamethasone or IV methylprednisolone. Long-term video electroencephalography (EEG) was assessed via novel ordinal scales for five features: seizure semiology/burden, epileptiform activity, slowing, organization, and sleep architecture. We abstracted parental assessment of functional domains (i.e., cognition) from the medical records. Pre-treatment and post-treatment EEG features, functional domains, and treatment regimens were compared. Thirty-five children with refractory epilepsy were included. Overall, 16/35 (46%) of individuals had a >50% reduction in seizure frequency from the pre-treatment EEG to the initial post-treatment EEG. In particular, tonic seizures (in a subset of 23 children) were reduced (24-hour tonic seizure count pre-treatment was 8 [4-13] and 3 [1-5] post-treatment EEG#1, p=0.04). For follow-up post-treatment EEGs, there was: (1) better formation of sleep spindles (37% normal pre-treatment to 63% normal post-treatment; p=0.04); and (2) improvement in parental reported cognition (in 43%). Improved cognition was the only outcome that differed between the dexamethasone and methylprednisolone treated groups (58% for dexamethasone [n=11/19] vs. 25% for methylprednisolone [n=4/16]; p=0.03). Large studies should be powered to detect reductions in seizures (particularly tonic as we identified a 2.6-fold reduction), improved EEG organization, and improved sleep architecture (21 percentage points). Cognitive improvements following steroid treatment, reported by parents, should be quantified and fully characterized in future work.

Based on a multicenter cohort of people with anti-NMDA receptor encephalitis (anti-NMDARE), we describe seizure phenotypes, electroencephalographic (EEG) findings, and anti-seizure treatment strategies. We also investigated whether specific electrographic features are associated with persistent seizures or status epilepticus after acute presentation. In this retrospective cohort study, we reviewed records of children and adults with anti-NMDARE between 2010 and 2014 who were included in the Rare Epilepsy of New York City database, which included the text of physician notes from five academic medical centers. Clinical history (e.g., seizure semiology) and EEG features (e.g., background organization, slowing, epileptiform activity, seizures, sleep architecture, extreme delta brush) were abstracted. We compared clinical features associated with persistent seizures (ongoing seizures after one month from presentation) and status epilepticus, using bivariate and multivariable analyses. Among the 38 individuals with definite anti-NMDARE, 32 (84%) had seizures and 29 (76%) had seizures captured on EEG. Electrographic-only seizures were identified in five (13%) individuals. Seizures started at a median of four days after initial symptoms (IQR: 3-6 days). Frontal lobe-onset focal seizures were most common (n=12; 32%). Most individuals (31/38; 82%) were refractory to anti-seizure medications. Status epilepticus was associated with younger age (15 years [9-20] vs. 23 years [18-27]; p=0.04) and Hispanic ethnicity (30 [80%] vs. 8 [36%]; p=0.04). Persistent seizures (ongoing seizures after one month from presentation) were associated with younger age (nine years [3-14] vs. 22 years [15-28]; p<0.01). Measured electrographic features were not associated with persistent seizures. Seizures associated with anti-NMDARE are primarily focal seizures originating in the frontal lobes. Younger patients may be at increased risk of epileptogenesis and status epilepticus. Continuous EEG monitoring helps identify subclinical seizures, but specific EEG findings may not predict the severity or persistence of seizures during hospitalization.