We report our pediatric experience with lacosamide, a new antiepileptic drug, approved by the US Food and Drug Administration as adjunctive therapy in focal epilepsy in patients more than 17 years ...old. We retrospectively reviewed charts for lacosamide use and seizure frequency outcome in patients with focal epilepsy (Wilcoxon signed rank test). Sixteen patients (7 boys) were identified (median dose 275 mg daily, 4.7 mg/kg daily; mean age 14.9 years, range 8-21 years). Patients were receiving a median of 2 antiepileptic drugs (interquartile range IQR 1.7-3) in addition to having undergone previous epilepsy surgery ( n = 3), vagus nerve stimulation ( n = 9), and ketogenic diet ( n = 3). Causes included structural (encephalomalacia and diffuse encephalitis, 1 each; stroke in 2) and genetic abnormalities (Aarskog and Rett syndromes, 1 each) or cause not known ( n = 10). Median seizure frequency at baseline was 57 per month (IQR 7-75), and after a median follow-up of 4 months (range 1-13 months) of receiving lacosamide, it was 12.5 per month (IQR 3-75), ( P < 0.01). Six patients (37.5%; 3 seizure free) were classified as having disease that responded to therapy (≥50% reduction seizure frequency) and 10 as having disease that did not respond to therapy (<50% in 3; increase in 1; unchanged in 6). Adverse events (tics, behavioral disturbance, seizure worsening, and depression with suicidal ideation in 1 patient each) prompted lacosamide discontinuation in 4/16 (25%). This retrospective study of 16 children with drug-resistant focal epilepsy demonstrated good response to adjunctive lacosamide therapy (median seizure reduction of 39.6%; 37.5% with ≥50% seizure reduction) without severe adverse events.
Rufinamide is a new antiepileptic drug recently approved as adjunctive treatment for generalized seizures in Lennox-Gastaut syndrome. We undertook a retrospective analysis of 77 patients with ...refractory epilepsy and receiving rufinamide to evaluate the drug's efficacy, tolerability, safety, and dosing schedules. It appeared efficacious in diverse epilepsy syndromes, with the highest responder rate in focal cryptogenic epilepsies (81.1% of patients with >50% response rate), and in diverse seizure types, with the highest responder rate in tonic/atonic and partial seizures (48.6% and 46.7% of patients with >50% response rate, respectively). Rufinamide was well tolerated: only 13% of patients developed side effects necessitating drug withdrawal. These findings suggest that rufinamide may possess good efficacy and tolerability, and that its efficacy may extend to epilepsy syndromes beyond Lennox-Gastaut, including both partial and generalized epilepsy syndromes.
Abstract Objective Patients with repaired tetralogy of Fallot account for a substantial proportion of cases with late-onset right ventricular failure. The current surgical approach, which includes ...pulmonary valve replacement/insertion, has yielded mixed results. Therefore, it may be clinically useful to identify parameters that can be used to predict right ventricular function response to pulmonary valve replacement. Methods Cardiac magnetic resonance data before and 6 months after pulmonary valve replacement were obtained from 16 patients with repaired tetralogy of Fallot (8 male, 8 female; median age, 42.75 years). Right ventricular ejection fraction change from pre- to postpulmonary valve replacement was used as the outcome. The patients were divided into group 1 (n = 8, better outcome) and group 2 (n = 8, worst outcome). Cardiac magnetic resonance–based patient-specific computational right ventricular/left ventricular models were constructed, and right ventricular mechanical stress and strain, wall thickness, curvature, and volumes were obtained for analysis. Results Our results indicated that right ventricular wall stress was the best single predictor for postpulmonary valve replacement outcome with an area under the receiver operating characteristic curve of 0.819. Mean values of stress, strain, wall thickness, and longitudinal curvature differed significantly between the 2 groups with right ventricular wall stress showing the largest difference. Mean right ventricular stress in group 2 was 103% higher than in group 1. Conclusions Computational modeling and right ventricular stress may be used as tools to identify right ventricular function response to pulmonary valve replacement. Large-scale clinical studies are needed to validate these preliminary findings.
Objective Patients with repaired tetralogy of Fallot account for most cases of late-onset right ventricle failure. The current surgical approach, which includes pulmonary valve replacement/insertion, ...has yielded mixed results. A new surgical option of placing an elastic band in the right ventricle is proposed to improve right ventricular cardiac function as measured by the ejection fraction. Methods A total of 20 computational right ventricular/left ventricular/patch/band combination models using cardiac magnetic resonance imaging from a patient with tetralogy of Fallot were constructed to investigate the effect of band material stiffness variations, band length, and active contraction. These models included 4 different band material properties, 3 band length, 3 active contracting band materials, and models with patch and scar replaced by contracting tissue. Results Our results indicated that the band insertion, combined with active band contraction and tissue regeneration techniques that restore right ventricular myocardium, has the potential to improve right ventricular ejection fraction by 7.5% (41.63% ejection fraction from the best active band model to more than 34.10% ejection fraction from baseline passive band model) and 4.2% (41.63% from the best active band model compared with cardiac magnetic resonance imaging-measured ejection fraction of 37.45%). Conclusions The cardiac magnetic resonance imaging-based right ventricular/left ventricular/patch/band model provides a proof of concept for using elastic bands to improve right ventricular cardiac function. Band insertion, combined with myocardium regeneration techniques and right ventricular remodeling surgical procedures, has the potential to improve ventricular function in patients with repaired tetralogy of Fallot and other similar forms of right ventricular dysfunction after surgery. Additional investigations using in vitro experiments, animal models, and, finally, patient studies are warranted.
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