Spike height improves prediction of future seizure risk.

OBJECTIVE: We evaluated whether interictal epileptiform discharge (IED) rate and morphological characteristics predict seizure risk. METHODS: We evaluated 10 features from automatically detectable IEDs in a stereotyped population with self-limited epilepsy with centrotemporal spikes (SeLECTS). We tested whether the average value or the most extreme values from each feature predicted future seizure risk in cross-sectional and longitudinal models. RESULTS: 10,748 individual centrotemporal IEDs were analyzed from 59 subjects at 81 timepoints. In cross-sectional models, increases in average spike height, spike duration, slow wave rising slope, slow wave falling slope, and the most extreme values of slow wave rising slope each improved prediction of an increased risk of a future seizure compared to a model with age alone (p < 0.05, each). In longitudinal model, spike rising height improved prediction of future seizure risk compared to a model with age alone (p = 0.04) CONCLUSIONS: Spike height improves prediction of future seizure risk in SeLECTS. Several other morphological features may also improve prediction and should be explored in larger studies. SIGNIFICANCE: Discovery of a relationship between novel IED features and seizure risk may improve clinical prognostication, visual and automated IED detection strategies, and provide insights into the underlying neuronal mechanisms that contribute to IED pathology.

Diazepam induced sleep spindle increase correlates with cognitive recovery in a child with epileptic encephalopathy.

BACKGROUND: Continuous spike and wave of sleep with encephalopathy (CSWS) is a rare and severe developmental electroclinical epileptic encephalopathy characterized by seizures, abundant sleep activated interictal epileptiform discharges, and cognitive regression or deceleration of expected cognitive growth. The cause of the cognitive symptoms is unknown, and efforts to link epileptiform activity to cognitive function have been unrevealing. Converging lines of evidence implicate thalamocortical circuits in these disorders. Sleep spindles are generated and propagated by the same thalamocortical circuits that can generate spikes and, in healthy sleep, support memory consolidation. As such, sleep spindle deficits may provide a physiologically relevant mechanistic biomarker for cognitive dysfunction in epileptic encephalopathies. CASE PRESENTATION: We describe the longitudinal course of a child with CSWS with initial cognitive regression followed by dramatic cognitive improvement after treatment. Using validated automated detection algorithms, we analyzed electroencephalograms for epileptiform discharges and sleep spindles alongside contemporaneous neuropsychological evaluations over the course of the patient's disease. We found that sleep spindles increased dramatically with high-dose diazepam treatment, corresponding with marked improvements in cognitive performance. We also found that the sleep spindle rate was anticorrelated to spike rate, consistent with a competitively shared underlying thalamocortical circuitry. CONCLUSIONS: Epileptic encephalopathies are challenging electroclinical syndromes characterized by combined seizures and a deceleration or regression in cognitive skills over childhood. This report identifies thalamocortical circuit dysfunction in a case of epileptic encephalopathy and motivates future investigations of sleep spindles as a biomarker of cognitive function and a potential therapeutic target in this challenging disease.