Summary:Purpose: To study pharmacokinetics of levetiracetam (LEV) during pregnancy, delivery, lactation, and in the neonatal period.Methods: Fourteen women with epilepsy receiving LEV treatment during pregnancy and lactation contributed with 15 pregnancies to this prospective study in which LEV concentrations in plasma and breast milk were determined. Trough maternal plasma samples were collected each trimester, and at baseline after delivery. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from newborns during 2 days after delivery. LEV concentration was also determined in breast milk and in plasma collected from 11 of the mothers and their suckling infants after birth.Results: The umbilical cord/maternal plasma concentration ratios ranged from 0.56-2.0 (mean 1.15, n = 13). LEV plasma concentrations in the neonates declined with an estimated halflife of 18 h (n = 13). The mean milk/maternal plasma concentration ratio was 1.05 (range, 0.78-1.55, n = 11). The infant dose of LEV was estimated to 2.4 mg/kg/day, equivalent to 7.9% of the weight-normalized maternal dose. Plasma concentrations in breastfed were approximately 13% of the mother's plasma levels. Maternal plasma concentrations during third trimester were only 40% of baseline concentrations outside pregnancy (p < 0.001, n = 7)Conclusions: Our observations suggest considerable transplacental transport of LEV and fairly slow elimination in the neonate. Plasma concentrations of LEV in nursed infants are low despite an extensive transfer of LEV into breast milk. Pregnancy appears to enhance the elimination of LEV resulting in marked decline in plasma concentration, which suggests that therapeutic monitoring may be of value.

Objective:To investigate prospective, population-based long-term outcomes concerning seizures and antiepileptic drug (AED) treatment after resective epilepsy surgery in Sweden.Methods:Ten- and 5-year follow-ups were performed in 2005 to 2007 for 278/327 patients after resective epilepsy surgery from 1995 to 1997 and 2000 to 2002, respectively. All patients had been prospectively followed in the Swedish National Epilepsy Surgery Register. Ninety-three patients, who were presurgically evaluated but not operated, served as controls.Results:In the long term (mean 7.6 years), 62% of operated adults and 50% of operated children were seizure-free, compared to 14% of nonoperated adults (p < 0.001) and 38% of nonoperated children (not significant). Forty-one percent of operated adults and 44% of operated children had sustained seizure freedom since surgery, compared to none of the controls (p < 0.0005). Multivariate analysis identified ≥30 seizures/month at baseline and long epilepsy duration as negative predictors and positive MRI to be a positive predictor of long-term seizure-free outcome. Ten years after surgery, 86% of seizure-free children and 43% of seizure-free adults had stopped AEDs in the surgery groups compared to none of the controls (p < 0.0005).Conclusions:This population-based, prospective study shows good long-term seizure outcomes after resective epilepsy surgery. The majority of the patients who are seizure-free after 5 and 10 years have sustained seizure freedom since surgery. Many patients who gain seizure freedom can successfully discontinue AEDs, more often children than adults.Classification of evidence:This study provides Class III evidence that more patients are seizure-free and have stopped AED treatment in the long term after resective epilepsy surgery than nonoperated epilepsy patients.

Summary:Purpose: To assess the additional value of subtraction ictal single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM) for localization of the epileptogenic zone in patients with drug-resistant epilepsy scheduled for invasive video-EEG (VEEG) before epilepsy surgery by a descriptive study from clinical practice.Methods: Forty-nine consecutive epilepsy patients between January 2000 and March 2006 were included. Thirty-six of the 49 patients were offered surgery, and 34 underwent resective surgery during the study period. Localizing and outcome data are presented from 31 patients with a follow-up period of ≥12 months. Successful ictal SPECT was performed in 26 patients, and SISCOM showed significant hyperperfusions with 3.5 SD above reference. Twenty patients had SISCOM-guided electrode placement, invasive monitoring, and 1-year postsurgical followup data. Two independent epileptologists evaluated whether SISCOM results (a) altered the hypothesis and extended the strategy for electrode placement at invasive recording, or (b) were confirmatory of other localizing data and did not alter the strategy. We defined that SISCOM had an impact on seizure outcome if the seizure-onset zone was seen in electrodes overlying a brain region with a significant hyperperfusion. When SISCOM was concordant with ictal onset in the extended electrodes, SISCOM was considered a prerequisite for the outcome at postoperative follow-up.Results: SISCOM findings altered and extended the strategy for electrode placement at invasive recording in 15 patients (group A). SISCOM was a prerequisite for seizure outcome in all six patients with favorable outcomes. Nine patients had poor results from surgery in this group; SISCOM was concordant with invasive VEEG in six patients, and discordant with invasive VEEG in three patients. SISCOM findings were confirmatory with other localizing data and did not alter the strategy at invasive recording in five patients (group B). Two patients had favorable surgical outcomes. In this group, three patients had poor results; SISCOM and other localizing findings were concordant with invasive VEEG in one patient and discordant with invasive VEEG in two patients.Conclusions: SISCOM is valuable for the identification of the epileptogenic zone in patients with drug-resistant epilepsy scheduled for invasive VEEG. SISCOM analysis was either a prerequisite for favorable result or concordant with other localizing methods in all patients with favorable seizure outcome at 1 year of follow-up [40%; confidence interval (CI), 19-64). Key Words: Epilepsy-Ictal SPECT-SISCOMSurgical outcome.Epilepsy surgery is successful in ∼70-80% of operatedon patients. The likelihood of seizure freedom is higher if an epileptogenic lesion has been identified on MRI during the presurgical workup (Engel et al., 1993). During the last decade, enhanced diagnostic sensitivity by advances in neuroimaging has reduced the proportion of patients with normal MRIs and has led to a decrease in the need for invasive video-EEG (...