Pediatric Palliative Epilepsy Surgery: A Report From the Pediatric Epilepsy Research Consortium (PERC) Surgery Database.

BACKGROUND: Epilepsy surgery is an underutilized resource for children with drug-resistant epilepsy. Palliative and definitive surgical options can reduce seizure burden and improve quality of life. Palliative epilepsy surgery is often seen as a "last resort" compared to definitive surgical options. We compare patient characteristics between palliative and definitive epilepsy surgical patients and present palliative surgical outcomes from the Pediatric Epilepsy Research Consortium surgical database. METHODS: The Pediatric Epilepsy Research Consortium Epilepsy Surgery database is a prospective registry of patients aged 0-18 years undergoing evaluation for epilepsy surgery at 20 pediatric epilepsy centers. We included all children with completed surgical therapy characterized as definitive or palliative. Demographics, epilepsy type, age of onset, age at referral, etiology of epilepsy, treatment history, time-to-referral/evaluation, number of failed anti-seizure medications (ASMs), imaging results, type of surgery, and postoperative outcome were acquired. RESULTS: Six hundred forty patients undergoing epilepsy surgery were identified. Patients undergoing palliative procedures were younger at seizure onset (median: 2.1 vs 4 years, P= 0.0008), failed more ASM trials before referral for presurgical evaluation (P=<0.0001), and had longer duration of epilepsy before referral for surgery (P=<0.0001). During presurgical evaluation, patients undergoing palliative surgery had shorter median duration of video-EEG data collected (P=0.007) but number of cases where ictal data were acquired was similar between groups. The most commonly performed palliative procedure was corpus callosotmy (31%), followed by lobectomy (21%) and neuromodulation (82% responsive neurostimulation vs 18% deep brain stimulation). Palliative patients were further categorized into traditionally palliative procedures vs traditionally definitive procedures. The majority of palliative patients had 50% reduction or better in seizure burden. Seizure free outcomes were significantly higher among those with traditional definitive surgeries, 41% (95% confidence interval: 26% to 57%) compared with traditional palliative surgeries and 9% (95% confidence interval: 2% to 17%). Rate of seizure freedom was 46% at 24 months or greater of follow-up in the traditional definitive group. CONCLUSIONS: Patients receiving palliative epilepsy surgery trialed more ASMs, were referred later after becoming drug resistant, and had longer gaps between drug resistance and epilepsy surgery compared with patients undergoing definitive epilepsy surgery. The extent of surgical evaluation is impacted if surgery is thought to be palliative. A majority of palliative surgery patients achieved >50% seizure reduction at follow-up, both in groups that received traditionally palliative and traditionally definitive surgical procedures. Palliative surgical patients can achieve greater seizure control and should be referred to an epilepsy surgery center promptly after failing two appropriate anti-seizure medications.

US Generic Antiseizure Medication Supply Chain: Observations from Analysis of US Government Databases.

BACKGROUND: Generic drug manufacturing has shifted away from the U.S. in the last few decades. The medication supply chain, from manufacturers to resellers, has become increasingly globalized and complex. This has led to bottlenecks in their manufacture resulting in medication shortages. Review of this process as it pertains to antiseizure medications (ASM) shows gaps in our comprehension of its complexities. Understanding these processes will be essential for preventing medication shortages. OBJECTIVES: The aim of this research is to examine the generic ASM supply with an emphasis on production, labeling, and repackaging. METHODS: Data from the United States Food and Drug Administration (FDA) and the National Library of Medicine (NLM) website DailyMed was used to evaluate supply chain details to gather information on antiseizure medication formulations, manufacturing locations, and labeling. RESULTS: Out of 3142 ASM-related active National Drug Code (NDC-9) codes, 2663 NDC-9 codes with Abbreviated New Drug Application (ANDA) status were included in the analysis. Most (94.8 %) were enteral, with only 5.2 % being parenteral (intravenous and intramuscular route). We identified the manufacturing country for 82 % of these codes, corresponding to 306 unique ANDA numbers. 119 manufacturing sites in 12 countries produce generic ASM Finished Dosage Forms (FDF): 103 for enteral and 21 for parenteral. India is the main producer of enteral ASM FDFs with 49 sites, followed by the US with 36. Regarding parenteral formulation, five countries had 21 unique manufacturing locations. 42 % of the 103 enteral ASM FDFs manufacturing sites produced multiple ASM FDFs, with one facility making eight distinct ASMs. 34.4 % of facilities were associated with over 3 ANDAs, and 15.1 % with more than 5. 22.7 % of ANDAs lacked a manufacturing facility identifier. Repackaged ASM FDFs constituted 48 % of NDC-9 s. Gabapentin and pregabalin were the most common oral ASMs. CONCLUSIONS: India is the major source for generic ASM FDFs manufacturing, leading to concerns about overall supply dependency on that country. There is a paucity of facilities for the global supply of parenteral ASM FDFs. There is missing data for many NDC-9 codes emphasizing urgency for transparency in the supply chain.

Neural representations of self-perception of voice: An intracortical evoked potential analysis based on an adolescent with right temporal lobe epilepsy.

INTRODUCTION: The neural bases for language perception have been studied elsewhere using Transcranial Magnetic Stimulation, functional Magnetic Resonance Imaging and Direct Cortical Stimulation. However, to our knowledge, there is no previous report about a patient identifying the change in his voice tone, speed, and prosody because of right temporal cortical stimulation. Nor has there been a cortico-cortical evoked potential (CCEP) assessment of the network underlying this process. CASE REPORT: We present CCEP from a patient with right focal refractory temporal lobe epilepsy of tumoral etiology who reported changes in the perception of his own speech prosody during stimulation. This report will serve as a complement to the understanding of the neural networks of language and prosody. CONCLUSION: The present report shows that right superior temporal gyrus, transverse temporal gyrus, right amygdala, hippocampus, and fusiform gyrus (FG) are part of the neural network subjacent to own human voice perception.

Pearls & Oy-sters: Harnessing New Diagnostic and Therapeutic Approaches to Treat a Patient With Genetic Drug-Resistant Focal Epilepsy.

Focal cortical dysplasia (FCD) is a congenital developmental malformation and is one of the leading causes of drug-resistant focal epilepsy (DRFE). Although focal epilepsies traditionally have been regarded as acquired disorders, increasing evidence suggests a substantial genetic contribution to the pathogenesis of focal structural epilepsies, including FCDs. Variations in the Dishevelled, Egl-10, and domain-containing protein 5 (DEPDC5) have recently emerged as a causative gene mutation in familial focal epilepsies associated with FCD type 2a, including bottom-of-sulcus dysplasia (BOSD). We present the case of a 20-year-old man with DRFE, positive for DEPDC5 c.1555C>T (p.GIn519*) heterozygous pathogenic variant. Initial 3T brain MRI was unrevealing, but subsequent 7T MRI including 7T edge-enhancing gradient echo revealed a left superior frontal sulcus BOSD concordant with the electroclinical data. The patient underwent treatment with MR-guided laser interstitial thermal ablation of the left frontal BOSD without intracranial EEG monitoring (skipped candidate), resulting in a seizure-free outcome of 9 months since the last follow-up. Our case highlights the real-world application of summative information obtained through advancements in epilepsy genetic testing, minimally invasive surgeries, and ultra-high field MRI, allowing us to provide a safe and effective treatment for a patient with a genetic DRFE.