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 Retrospective review was performed of children aged <3 years with epileptic spasms at our center from 2004-2010. Short-term (<6 months) and long-term (≥6 months) outcomes were assessed. We ...included 173 children (104 boys; median age of onset, 6.8 months) with epileptic spasms of known (62%) and unknown (38%) etiology. Treatments included adrenocorticotropic hormone (n = 103), vigabatrin (n = 82), phenobarbital (n = 34), and other agents (n = 121). Short-term treatment with adrenocorticotropic hormone and vigabatrin provided better epileptic spasm control in groups with known and unknown etiology than other agents. At follow-up (6-27 months), 54% of children manifested seizures, and 83% manifested developmental delay. Known etiology was a predictor of poor developmental outcome ( P = 0.006), whereas bilateral/diffuse brain lesions predicted both poor development and seizures ( P = 0.001 and 0.005, respectively). Initial presentations of epileptic spasms with hypotonia or developmental delay most strongly predicted both seizures and neurodevelopmental outcomes ( P < 0.001). In a child presenting with epileptic spasms with developmental delay or hypotonia, no specific treatment may offer superior benefit.
The objective of this study was to assess the feasibility of magnetoencephalography in epilepsy patients with a vagus nerve stimulator. Magnetoencephalography was performed in two patients with ...medically intractable epilepsy who had a vagus nerve stimulator. Because of the artifacts caused by the vagus nerve stimulator, no spikes could be identified in the original magnetoencephalographic data in either patient. The temporally extended signal space separation method was used to remove artifacts. After processing by this method, left temporoparietal spikes were clearly identified in patient 1. Equivalent current dipoles calculated from these spikes were localized in the left posterior-temporal and parietal lobes. The location of the dipoles was consistent with the spike distribution on intracranial electroencephalography. In patient 2, bilateral diffuse spikes were seen in the processed data. The contour maps demonstrated a bilateral pattern, not in agreement with a single focal source. These findings supported the diagnosis of symptomatic generalized epilepsy in this patient. Magnetoencephalography may thus be a useful option for evaluating patients with intractable epilepsy who have a vagus nerve stimulator.
Prader-Willi syndrome is a chromosomal disorder caused by absence of expression of the paternal active genes in the 15q11∼q13 chromosome region; it is associated with an increased incidence of ...epilepsy and narcolepsy. Presented here is the case of a 2.5-year-old boy with Prader-Willi syndrome and a history of neonatal superior sagittal sinus thrombosis with new onset of atonic seizures with electrographic onset from the parasagittal region. It is postulated that microscarring from neonatal venous sinus thrombosis, history of febrile seizures, and Prader-Willi syndrome are factors predisposing him to epilepsy. The importance of video electroencephalography with electromyography electrodes is emphasized for Prader-Willi syndrome patients with drop episodes, to differentiate cataplexy from seizures. This being a novel report of a Prader-Willi syndrome patient with atonic seizures, the literature on seizure semiology among patients with Prader-Willi syndrome is reviewed.
Abstract Background Hemispherectomy is a surgical procedure used to treat medically intractable epilepsy in children with severe unilateral cortical disease secondary to acquired brain or congenital ...lesions. The major surgical approaches for hemispherectomy are anatomic hemispherectomy, traditional functional hemispherectomy, and peri-insular hemispherotomy. We describe the epilepsy outcome, including the need for reoperation, after hemispherectomy in patients with brain malformations or acquired brain lesions who underwent hemispherectomy for refractory epilepsy. Methods We conducted a retrospective observational study at Children's Hospital Boston. Cases were ascertained from a research database of patients who underwent epilepsy surgery from 1997 to 2011. Data were obtained from electronic medical records and office charts. Outcome after surgery was defined as improvement in seizures (quantity and severity) represented by the Engel classification score measured at last follow-up, with a minimum of 12 months of follow-up. The need for reoperation for completion of hemispheric disconnection. We also examined whether placement of ventriculoperitoneal shunt was required after hemispherectomy was a secondary outcome. Results We identified 36 patients who underwent hemispherectomy for severe, medically intractable epilepsy. Group 1 (n = 14) had static acquired lesions, and group 2 (n = 22) had malformations of cortical development. Mean age at surgery for group 1 was 9 years (S.D. 5.5) and 2.77 years for group 2 (S.D. 4.01; P < 0.001). The seizure outcome was good in both groups (Engel score I for 25, II for three, III for six, and IV for two patients) and did not differ between the two groups. In group 1, five patients underwent anatomic hemispherectomy (one had prior focal resection), four underwent functional hemispherectomy, and five underwent peri-insular hemispherotomy; none required a second procedure. In group 2, a total of 14 patients had anatomic hemispherectomy (of these, three had had limited prior focal resection), five had functional hemispherectomy, and three had peri-insular hemispherotomy. Among the patients in group 2 who had had functional hemispherectomy, one required reoperation to complete the disconnection and one required peri-insular hemispherotomy because of persistent seizures. In group 1, three patients underwent a ventriculoperitoneal shunt, and from these patients two underwent anatomic hemispherectomy and one had functional hemispherectomy. In group 2, 12 patients had ventriculoperitoneal shunt, and all of them had anatomic hemispherectomy as a first or second procedure. Conclusion Seizure outcome after hemispherectomy is good in patients with acquired lesions and with developmental malformations. Although the seizure outcome was similar in the three procedures, the complication rate was higher with anatomic hemispherectomy than with the more recent functional hemispherectomy and peri-insular hemispherotomy. The group with cortical malformations generally had surgery at a younger age; two patients with malformations of cortical development who underwent functional hemispherectomy required second surgeries. The need for reoperation in these cases may reflect the anatomic complexity of developmental hemispheric malformations, which may lead to incomplete disconnection.
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