Development and Validation of a Model to Predict Regression of Large Size Hepatocellular Adenoma.

INTRODUCTION: Surgery is advocated in hepatocellular adenomas (HCA) >5 cm that do not regress to <5 cm after 6-12 months. The aim of this study was to develop a model for these patients, estimating the probability of HCA regression to <5 cm at 1 and 2 years follow-up. METHODS: Data were derived from a multicenter retrospective cohort of female patients diagnosed with HCA >5 cm at first follow-up. Potential predictors included age, body mass index, and HCA diameter at diagnosis (T0), HCA-subtype (hepatocyte nuclear factor 1α inactivated HCA, inflammatory-HCA, unclassified HCA) and "T0-T1 regression-over-time" (percentage of regression between T0 and first follow-up (T1) divided by weeks between T0 and T1). Cox proportional hazards regression was used to develop a multivariable model with time to regression of HCA < 5 cm as outcome. Probabilities at 1 and 2 years follow-up were calculated. RESULTS: In total, 180 female patients were included. Median HCA diameter at T0 was 82.0 mm and at T1 65.0 mm. Eighty-one patients (45%) reached the clinical endpoint of regression to <5 cm after a median of 34 months. No complications occurred during follow-up. In multivariable analysis, the strongest predictors for regression to <5 cm were HCA diameter at T0 (logtransformed, hazard ratio (HR) 0.05), T0-T1 regression-over-time (HR 2.15) and HCA subtype inflammatory-HCA (HR 2.93) and unclassified HCA (HR 2.40), compared to hepatocyte nuclear factor 1α inactivated HCA (reference). The model yielded an internally validated c-index of 0.79. DISCUSSION: In patients diagnosed with HCA > 5 cm that still exceed 5 cm at first follow-up, regression to <5 cm can be predicted at 1 and 2 years follow-up using this model. Although external validation in an independent population is required, this model may aid in decision-making and potentially avoid unnecessary surgery.

Continuous spike-waves during slow-wave sleep in a mouse model of focal cortical dysplasia.

OBJECTIVE: To examine if mice with focal cortical dysplasia (FCD) develop spontaneous epileptic seizures and, if so, determine the key electroencephalography (EEG) features. METHODS: Unilateral single freeze lesions to the S1 region (SFLS1R) were made in postnatal day 0-1 pups to induce a neocortical microgyrus in the right cortical hemisphere. Continuous 24-h recordings with intracranial EEG electrodes and behavioral tests were performed in adult SFLS1R and sham-control mice to assess neurologic status. RESULTS: A high percentage of adult SFLS1R animals (89%, 40/45) exhibited at least one or more spontaneous nonconvulsive seizure events over the course of 24 h. Of these animals, 60% (27/45) presented with a chronic seizure state that was persistent throughout the recording session, consisting of bursts of rhythmic high-amplitude spike-wave activities and primarily occurring during periods of slow-wave sleep. In comparison, none of the control, age-matched, mice (0/12) developed seizures. The epileptic discharge pattern closely resembled a pattern of continuous spike-waves during slow-wave sleep (CSWS) of the human syndrome described as an electrical status epilepticus during slow-wave sleep (ESES). Key findings in the SFLS1R model indicated that the observed CSWS (1) were more prevalent in female (18/23) versus male (9/22, p < 0.05), (2) were strongest in the right S1 region although generalized to other brain regions, (3) were associated with significant cognitive and behavioral deficits, (4) were temporarily alleviated by ethosuximide treatment or optogenetic activation of cortical γ-aminobutyric acid (GABA)ergic neurons, and (5) theta and alpha band rhythms may play a key role in the generalization of spike-wave activities. SIGNIFICANCE: This is the first report of an in vivo animal FCD model that induces chronic spontaneous electrographic brain seizures. Further characterization of the abnormal oscillations in this mouse model may lead to a better understanding of the mechanisms of CSWS/ESES.