Efficacy and tolerability of perampanel as a first add-on therapy with different anti-seizure drugs.

PURPOSE: To investigate the efficacy and tolerability of perampanel (PER) when administered as a first add-on therapy to patients with focal epilepsy or idiopathic generalized epilepsy (IGE) taking one other antiseizure drug (ASD). METHODS: This multicentre, retrospective, one-year observational study collected data from patients (≥12 years) who initiated treatment with PER as first add-on therapy. Patients had to be experiencing inadequate seizure control on ASD monotherapy and tried ≤3 ASD monotherapies before initiating PER. Multivariate logistic regression analyses were performed, adjusted for the number and type of previous seizures, duration and aetiology of epilepsy. RESULTS: Of the 149 patients included in the study (mean age 41 years; 54.4 % male), 118 (79.2 %) were still receiving PER as first add-on treatment after 12 months. Mean PER dose was 6.2 mg/day. At 12 months, 45.6 % were seizure-free and 84.6 % responders. A significant difference in seizure freedom rate was found between patients with IGE and patients with focal epilepsy, but not in responders. Reduced seizure control was observed when PER was administered with strong enzyme-inducing ASDs; conversely, increased seizure control was seen when the same dose of PER was combined with enzyme-inhibiting ASDs. The most frequent adverse events were dizziness (15.4 %), irritability (14.1 %) and drowsiness (14.1 %); no differences in tolerance were observed among different combinations. CONCLUSION: PER demonstrated a good efficacy and safety profile when used as a first add-on therapy in patients who did not respond to monotherapy. PER dose adjustments may optimize seizure control when combined with strong enzyme-inducing or enzyme-inhibiting ASDs.

Neurosonographic assessment of the corpus callosum as imaging biomarker of abnormal neurodevelopment in late-onset fetal growth restriction.

OBJECTIVE: To explore corpus callosum (CC) developmental differences by ultrasound in late-onset small fetuses compared with adequate for gestational age (AGA) controls. STUDY DESIGN: Ninety four small (estimated fetal weight <10th centile) and 71 AGA fetuses were included. Small fetuses were further subdivided into fetal growth restriction (IUGR, n = 64) and small for gestational age (SGA, n = 30) based on poor perinatal outcome factors, that is, birth weight <3rd centile and/or abnormal cerebroplacental ratio and/or uterine artery Doppler. The entire cohort was scanned to assess CC by transvaginal neurosonography obtaining axial, coronal and midsagittal images. CC length, thickness, total area and the areas after a subdivision in 7 portions were evaluated by semiautomatic software. Furthermore, the weekly average growth of the CC in each study group was calculated and compared. RESULTS: Small fetuses showed significantly shorter (small fetuses: 0.49 vs. AGA: 0.52; p < 0.01) and smaller CC (1.83 vs. 2.03; p < 0.01) with smaller splenium (0.47 vs. 0.55; p < 0.01) compared to controls. The CC growth rate was also reduced when compared to controls. Changes were more prominent in small fetuses with abnormal cerebroplacental Doppler suggesting fetal growth restriction. CONCLUSIONS: Neurosonographic assessment of CC showed significantly altered callosal development, suggesting in-utero brain reorganization in small fetuses. This data support the potential value of CC assessment by US to monitor brain development in fetuses at risk.