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Objective: Perampanel, an antiseizure drug with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist properties, may have a targeted effect in genetic epilepsies with overwhelming glutamate receptor activation. Epilepsies with loss of γ-aminobutyric acid inhibition (e.g., SCN1A), overactive excitatory neurons (e.g., SCN2A, SCN8A), and variants in glutamate receptors (e.g., GRIN2A) hold special interest. We aimed to collect data from a large rare genetic epilepsy cohort treated with perampanel, to detect possible subgroups with high efficacy., Methods: This multicenter project was based on the framework of NETRE (Network for Therapy in Rare Epilepsies), a web of pediatric neurologists treating rare epilepsies. Retrospective data from patients with genetic epilepsies treated with perampanel were collected. Outcome measures were responder rate (50% seizure reduction), and percentage of seizure reduction after 3 months of treatment. Subgroups of etiologies with high efficacy were identified., Results: A total of 137 patients with 79 different etiologies, aged 2 months to 61 years (mean = 15.48 ± 9.9 years), were enrolled. The mean dosage was 6.45 ± 2.47 mg, and treatment period was 2.0 ± 1.78 years (1.5 months-8 years). Sixty-two patients (44.9%) were treated for >2 years. Ninety-eight patients (71%) were responders, and 93 (67.4%) chose to continue therapy. The mean reduction in seizure frequency was 56.61% ± 34.36%. Sixty patients (43.5%) sustained >75% reduction in seizure frequency, including 38 (27.5%) with >90% reduction in seizure frequency. The following genes showed high treatment efficacy: SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, POLG1, POLG2, and NEU1. Eleven of 17 (64.7%) patients with Dravet syndrome due to an SCN1A pathogenic variant were responders to perampanel treatment; 35.3% of them had >90% seizure reduction. Other etiologies remarkable for >90% reduction in seizures were GNAO1 and PIGA. Fourteen patients had a continuous spike and wave during sleep electroencephalographic pattern, and in six subjects perampanel reduced epileptiform activity., Significance: Perampanel demonstrated high safety and efficacy in patients with rare genetic epilepsies, especially in SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, CDKL5, NEU1, and POLG, suggesting a targeted effect related to glutamate transmission., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: To compare the efficacy and safety of the ketogenic diet (KD) with standard adrenocorticotropic hormone (ACTH) treatment in infants with West syndrome., Methods: In this parallel-cohort (PC) randomized controlled trial (RCT), infants were randomly allocated to KD or high-dose ACTH. Those who could not be randomized were followed in a PC. Primary end point was electroclinical remission at day 28. Secondary end points were time to electroclinical remission, relapse after initial response, seizure freedom at last follow-up, adverse effects, and developmental progress., Results: One hundred one infants were included: 32 in the RCT (16 KD; 16 ACTH) and 69 in the PC (37 KD; 32 ACTH). Electroclinical remission at day 28 was similar between KD and ACTH (RCT: 62% vs 69%; PC: 41% vs 38%; combined cohort: 47% vs 48%; KD vs ACTH, respectively). In the combined cohort, time to electroclinical remission was similar between both treatments (14 days for KD, 16 days for ACTH). However, relapse rates were 16% (KD) and 43% (ACTH, P = 0.09), and seizure freedom at last follow-up was 40% (KD) and 27% (ACTH, P = 0.18). Adverse effects needing acute medical intervention occurred more often with ACTH (30% with KD, 94% with ACTH, P < 0.001). Age-appropriate psychomotor development and adaptive behavior were similar. Without prior vigabatrin (VGB) treatment, remission at day 28 was 47% (KD) and 80% (ACTH, P = 0.02); relapse rates were 29% (KD) and 56% (ACTH, P = 0.13). Consequently, seizure freedom at last follow-up was similar. In infants with prior VGB, seizure freedom at last follow-up was 48% (KD) and 21% (ACTH, P = 0.05)., Significance: The study is underpowered; therefore, its results should be interpreted with caution. KD is as effective as ACTH in the long term but is better tolerated. Without prior VGB treatment, ACTH remains the first choice to achieve short-term remission. However, with prior VGB, KD was at least as effective as ACTH in the short term and was associated with lower relapse rates in the long term; therefore, it represents an appropriate second-line treatment after VGB., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Tuberous sclerosis complex (TSC) is the most common cause of West syndrome (WS). Currently available treatment options are ineffective in the majority of affected infants and/or associated with potential serious side effects. Based on the assumption that mTOR overactivation results in increased neuroexcitability in TSC, mTOR inhibitors have been studied as antiseizure therapy. As a result, everolimus recently received approval for the adjunctive treatment of patients aged ≥2 years with refractory TSC-associated focal and secondary generalized seizures. However, efficacy and safety data for infants with TSC-associated WS are still lacking. Therefore, a prospective open-label observational study was initiated at our center, to evaluate everolimus add-on treatment in infants with TSC-associated WS, previously refractory to standard treatment. For this preliminary report, data from four male infants with TSC2 and a median observation period of 13 (range = 8-42) months after treatment initiation were analyzed. Two infants showed electroclinical remission until day 14 after everolimus treatment initiation. In one additional infant, hypsarrhythmia resolved. No relapse after initial response was documented. Developmental progress improved in three infants. Tolerability was similar to that described in older children. According to our preliminary results, everolimus appears to have the potential to treat successfully both spasms and hypsarrhythmia in infants with TSC-associated WS, contributing to better developmental progress., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Purpose: The current concept for hemispherotomy includes various lateral techniques and the vertical perithalamic hemispherotomy introduced by Delalande in 1992. We have chosen the vertical approach because of advantages that possibly influence outcome: the possibility to completely disconnect the hemisphere at the level of the thalamus obviating both the need to resect the insula and the need to open and dissect the subarachnoid space of the Sylvian fissure., Methods: We retrospectively analyzed prospectively collected data of all patients who underwent vertical hemispherotomy at the Vienna pediatric epilepsy center. Seizure outcome was classified according to the International League Against Epilepsy (ILAE) proposal 2001., Key Findings: Follow-up data of 40 patients (22 male/18 female; median age 5.5 years; range 4.4 months to 20.1 years) were analyzed. Hemispherotomy was left in 26 and right in 14 patients. The underlying pathology was ischemic vascular in 19, malformation of cortical development (MCD) in 11, and other pathology in 10. No serious intraoperative complications were encountered. Only two infants (5.0%) needed blood replacement. There was one death on the fourth day after surgery caused by intractable hyponatremic brain edema. Three patients developed cerebrospinal fluid (CSF) disturbances, but only one needed a permanent ventriculoperitoneal (VP) shunt (2.5%). For outcome analysis we included 37 of 40 children with at least 12 months of follow-up. Thirty-four (91.9%) of 37 children were seizure-free (class 1a) after a median follow-up time of 3.7 years (range 12 month to 14.8 years)., Significance: We confirm the efficacy and safety of vertical parasagittal hemispherotomy as described by Delalande in a consecutive series of patients treated at our center since 1998. In addition, complete disconnection of the hemisphere in patients with MCD and/or patients with significant involvement of the insula was possible without the complications usually reported with other techniques., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Purpose: A focal lesion in the splenium of the corpus callosum is a rare finding in patients with epilepsy. Intoxication with antiepileptic drugs, edema after generalized seizures, or a rapid change of antiepileptic drug levels have been proposed as possible mechanisms. The aim of the present study was to analyze the relationship between this lesion and possible etiologic factors., Patients and Methods: We analyzed the magnetic resonance imaging (MRI) scans of 1,050 patients undergoing prolonged video-EEG (electroencephalography) monitoring and identified 24 patients with a focal lesion in the splenium of the corpus callosum. Twenty-four age- and gender-matched temporal lobe epilepsy patients without such a lesion served as a control group. We evaluated the following parameters for their possible etiologic significance: epilepsy syndrome, seizure types in medical history, seizure frequency during the past year prior to admission for prolonged video-EEG monitoring, localization of interictal spikes and ictal EEG patterns in patients with focal epilepsies as documented during prolonged video-EEG-monitoring, seizure types and seizure frequency during prolonged video-EEG monitoring, past as well as current antiepileptic medication, withdrawal of antiepileptic drugs during monitoring including duration of medication withdrawal, and finally drug levels above the therapeutic range., Results: The parameters analyzed showed no significant difference between the group of patients with focal lesions in the splenium of the corpus callosum and the control group., Conclusion: We could not identify a single etiologic factor responsible for the lesion in the splenium of the corpus callosum.

Purpose: Ictal vomiting represents a rare clinical manifestation during seizures originating from the temporal lobes of the nondominant hemisphere. The precise anatomic structures responsible for generation of ictal vomiting remain to be clarified. Ictal single photon emission computed tomography (SPECT), which allows one to visualize the three-dimensional dynamic changes of regional cerebral blood flow (rCBF) associated with the ongoing epileptic activity, should be useful to study the brain areas activated during ictal vomiting., Methods: We performed ictal Tc-HMPAO SPECT scans in two patients with mesial temporal lobe epilepsy (MTLE) whose seizures were characterized by ictal retching and vomiting. MTLE was documented by typical clinical seizure semiology, interictal and ictal EEG findings, hippocampal atrophy on magnetic resonance imaging (MRI) scan, and a seizure-free outcome after selective amydalohippocampectomy. In both patients, seizures originated in the nondominant temporal lobe. We obtained accurate anatomic reference of rCBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. We used ictal SPECT studies in 10 patients with MTLE who had seizures without ictal vomiting as controls., Results: In the two patients with ictal vomiting, we found a significant hyperperfusion of the nondominant temporal lobe (inferior, medial, and lateral superior) and of the occipital region on ictal SPECT. In patients without ictal vomiting, on the contrary, these brain regions never were hyperperfused simultaneously., Conclusions: Ictal SPECT provides further evidence that activation of a complex cortical network, including the medial and lateral superior aspects of the temporal lobe, and maybe the occipital lobes, is responsible for the generation of ictal vomiting.

Purpose: To study the mechanisms of startle-induced supplementary sensorimotor area (SSMA) seizures., Methods: We present a patient investigated with indwelling subdural grid electrodes covering both the SSMA and the dorsolateral frontal lobe., Results: We found a simultaneous seizure onset in the right dorsolateral premotor cortex and the right SSMA. High-resolution magnetic resonance imaging (MRI) showed a small subcortical lesion adjacent to the right SSMA. The patient became seizure free after resection of the lesion and the ictal-onset zone., Conclusions: We conclude that an extended region of abnormally excitable tissue within the frontal lobe could facilitate the generation of startle-induced seizures. We speculate that a widespread epileptogenic zone could help to explain why some patients with SSMA or dorsolateral frontal lobe seizures are more likely to have startle-induced seizures.