Achieving seizure freedom following failure of several antiseizure medications (ASMs) is rare, with the likelihood of achieving further control decreasing with each successive ASM trial. When cases of drug-resistant epilepsy arise, a diagnostic procedure known as stereoelectroencephalography (sEEG) can be used to identify epileptogenic zones (EZ) within the brain. After localization of these zones, they can be targeted for future surgical intervention. Here, we describe a case of complete seizure freedom off medication after sEEG without resection or other therapeutic intervention. In 2017, a 36-year-old right-handed male presented with drug-resistant epilepsy stemming from prior traumatic brain injury. Due to ongoing seizures, in 2020 a robotic-assisted sEEG electrode placement procedure was employed to localize the seizure onset zone. During sEEG monitoring, a single event was captured where the patient had dysarthric speech, left arm dystonic flexion, and difficulty responding to questioning. Notably, this event had no sEEG correlate, suggesting seizure occurrence in a region not monitored by implanted electrodes, which prompted the placement of scalp electrodes following this event. However, no further clinical events consistent with seizure were provoked through the remainder of recording. Following the 13-day admission, the patient chose to self-discontinue all seizure medications and has remained seizure free as of October 2023, more than 3.5 years later. While sEEG is considered a relatively safe procedure for seizure localization in drug resistant epilepsy, the possibility of microlesions created by sEEG depth electrodes remains largely unexplored. Further evaluation should be performed into potential tissue injury produced by depth electrode insertion.

An increasing number of gene mutations associated with epilepsy have been identified, some linked to gray matter heterotopia-a common cause of drug-resistant epilepsy. Current research suggests that gene mutation-associated epilepsy should not be considered a contraindication for surgery in epilepsy patients. At present, stereoelectroencephalography-guided radiofrequency thermocoagulation is an important method to treat periventricular nodular heterotopia-associated drug-resistant epilepsy. We present a case of drug-resistant epilepsy, accompanied by periventricular nodular heterotopia and a heterozygous mutation of the RELN gene, successfully treated with radiofrequency thermocoagulation, resulting in a favorable outcome.

(1) Background: Hemispherotomy is the generally accepted treatment for hemispheric drug-resistant epilepsy (DRE). Lateral or vertical approaches are performed according to the surgeon\'s preference. Multiple technical variations have been proposed since Delalande first described his vertical technique. We propose a sub-insular variation of the vertical parasagittal hemispherotomy (VPH) and describe our case series of patients operated on using this procedure. (2) Methods: Data from a continuous series of patients with hemispheric DRE who were operated on by the senior author (CR) using the modified sub-insular VPH technique were analyzed retrospectively. Pre-operative demographic and epilepsy characteristics, functional outcome, and surgical complications were extracted from medical charts. (3) Results: Twenty-five patients were operated on between August 2008 and August 2023; 23 have at least 3 months of follow-up. Of this group, 20 (86.9%) patients are seizure-free. Only two patients developed postoperative hydrocephalus (8.7%). All patients who were able to walk autonomously preoperatively and 20 (86.9%) of those with follow-up were able to walk without assistance. A total of 17 (74%) patients were able to perform adapted social activities at the latest follow-up. (4) Conclusions: Modified sub-insular VPH is a successful surgical technique for hemispheric DRE with seizure freedom rates similar to the largest series reported in the literature. Compared to other series, patients who were operated on with our modified technique had a lower rate of postoperative hydrocephalus and excellent long-term motor and cognitive outcomes.

Ring chromosome 20 or r(20) syndrome is a rare chromosomal disorder, mainly characterized by childhood-onset drug-resistant epilepsy with typical electroencephalographic findings, followed by mild to severe cognitive-behavioral decline. Recent studies support a possible role of the dopaminergic system in the epileptogenesis of this syndrome. We report the case of a 13-year-old female with mosaic r(20) who showed typical disease onset and evolution and a remarkable electroclinical improvement with zonisamide. Epilepsy related to r(20) is often medically intractable. When valproate and lamotrigine are not effective, zonisamide could be further investigated as a therapeutic option, since it acts as antifocal and it has a potential role in the prevention of dopamine depletion.

Adverse drug reactions (ADRs) to antiseizure therapy can worsen the quality of life, reduce adherence, and potentially lead to treatment discontinuation and uncontrolled seizures.
The aim of the study was to develop a prognostic model for ADRs to antiseizure therapy in adult patients with epilepsy from Colombia.
This case-control study included adult patients with epilepsy, who were separated into two groups: one group with ADRs to antiseizure therapy (cases), as determined by a complete evaluation conducted by an epileptologist, and another group without ADRs (controls). Variables were analyzed to identify statistical differences between the two groups and were then selected to construct a prognostic model using logistic regression. The Bonferroni method was applied for multiple comparisons.
Three hundred fifty-four patients with epilepsy were studied. One hundred and fifty (42%) patients had ADRs and 204 (57%) patients did not have ADs. A total of 362 ADRs were reported, with a third of them being general symptoms and most frequently occurring with older-generation antiseizure drugs (58%). Female sex, drug-resistant epilepsy, LEV, and CZP were risk factors, whereras the presence of tumoral etiology, absence of seizure triggers, and VPA were identified as protective factors. A prognostic model was constructed using previously reported risk factors for ADRs to antiseizure therapy and other variables available in this population study. In the multivariable analysis, the number of previously used antiseizure drugs (1, 2, or ≥3), TPM, CZP, LEV, PHT, and female sex were predictors of ADRs. The corrected p-values were estimated by the Bonferroni method; however, not all the variables achieved statistical significance with this adjustment.
In adult patients with epilepsy from Colombia, we found that the number of previously used antiseizure drugs, TPM, CZP, LEV, PHT, and female sex were predictive factors for ADRs to antiseizure therapy.

BACKGROUND: The occurrence of both an intracranial aneurysm and epilepsy, especially drug-resistant epilepsy (DRE), is rare. Although the overall incidence of aneurysms associated with DRE is unclear, it is thought to be particularly infrequent in the pediatric population. Surgical ligation of the offending aneurysm has been reported in conjunction with resolving seizure activity, although few cases have cited a combined approach of aneurysm ligation and resection of an epileptogenic focus.
METHODS: We present the case of a 14-year-old female patient with drug-resistant temporal lobe epilepsy and an ipsilateral supraclinoid internal carotid artery aneurysm. Seizure semiology, electroencephalography monitoring, and magnetic resonance imaging all indicated a left temporal epileptogenic focus, in addition to an incidental aneurysm. The authors recommended a combined surgery involving resection of the temporal lesion and surgical clip ligation of the aneurysm. Near-total resection and successful ligation were achieved, and the patient has remained seizure free since surgery at 1 year postoperatively.
CONCLUSIONS: In patients with focal DRE and an adjacent intracranial aneurysm, a combined surgical approach involving both resection and surgical ligation can be used. Several surgical timing and neuroanesthetic considerations should be made to ensure the overall safety and efficacy of this procedure.

There are limited treatment options for drug-resistant epilepsy (DRE) in children. We performed a pilot study to investigate the tolerability and effectiveness of cathodal transcranial direct current stimulation (tDCS) in DRE. Twelve children with DRE of varied etiology underwent three to four daily sessions of cathodal tDCS. The seizure frequency at 2 weeks before and after tDCS was obtained from seizure diaries; clinic reviews at 3 and 6 months assessed any longer-term benefits or adverse effects. The spike wave index (SWI) was analyzed in the EEGs done immediately before and after tDCS on the first and last day of tDCS. One child remained seizure free for a year after tDCS. One child had reduced frequency of ICU admissions for status epilepticus for 2 weeks, likely due to reduced severity of seizures. In four children, an improvement in alertness and mood was reported for 2-4 weeks after tDCS. There was no benefit following tDCS in the other children. There were no unexpected or serious adverse effects in any child. Benefit was seen in two children, and the reasons for the lack of benefit in the other children need further study. It is likely that tDCS stimulus parameters will need to be tailored for different epilepsy syndromes and etiologies.

Genetic generalized epilepsies (GGEs) are thought to represent disorders of thalamocortical networks. There are currently no well-established non-pharmacologic treatment options for patients with drug-resistant GGE. NeuroPace\'s Responsive Neurostimulation (RNS) System was approved by the United States Food and Drug Administration to treat focal seizures with up to two ictal foci. We report on three adults with drug-resistant GGE who were treated with thalamic RNS. Given the severity of their epilepsies and the potential ictogenic role of the thalamus in the pathophysiology of GGE, the RNS System was palliatively implanted with leads in the bilateral anterior thalamic nuclei (ANT) of these patients. The ANT was selected because it was demonstrated to be a safe target. We retrospectively evaluated metrics including seizure frequency over 18-32 months. One patient required explantation due to infection. The other two patients were clinical responders. By the end of the observation period reported here, one patient was seizure-free for over 9 months. All three self-reported an improved quality of life. The clinical response observed in these patients provides \'proof-of-principle\' that GGE may be treatable with responsive thalamic stimulation. Our results support proceeding to a larger study investigating the efficacy and safety of thalamic RNS in drug-resistant GGE.

UNASSIGNED: New-onset refractory status epilepticus (NORSE) is associated with high morbidity and mortality. Despite extensive work-up, the underlying etiology remains unknown in 50% of affected individuals. Mitochondrial disorders represent rare causes of NORSE. Biallelic variants in FASTKD2 were reported as a cause of infantile encephalomyopathy with refractory epilepsy.
UNASSIGNED: In the study, we report a previously healthy 14-year-old with a new, homozygous FASTKD2 variant presenting with NORSE. Following a seizure-free period of 7 years, he experienced another super-refractory SE and subsequently developed drug-resistant focal epilepsy, mild myopathy, optic atrophy, and discrete psychomotor slowing. Structural MRI at the time of NORSE showed right temporo-parieto-occipital FLAIR hyperintensity and diffusion restriction, with extensive right hemispheric atrophy at the age of 22 years. Whole-exome sequencing revealed a novel homozygous loss of function variant [c.(1072C>T);(1072C>T)] [p.(Arg358Ter);(Arg358Ter)] in FASTKD2 (NM_001136193), resulting in a premature termination codon in the protein-coding region and loss of function of FASTKD2. Oxidative phosphorylation (OXPHOS) in muscle and skin fibroblasts was unremarkable.
UNASSIGNED: This is the first case of a normally developed adolescent with a new homozygous loss of function variant in FASTKD2, manifesting with NORSE. The phenotypical spectrum of FASTKD2-related mitochondrial disease is heterogeneous, ranging from recurrent status epilepticus and refractory focal epilepsy in an adolescent with normal cognitive development to severe forms of infantile mitochondrial encephalopathy. Although mitochondrial diseases are rare causes of NORSE, clinical features such as young age at onset and multi-system involvement should trigger genetic testing. Early diagnosis is essential for counseling and treatment considerations.

Background. Lennox-Gastaut syndrome (LGS) is a developmental and epileptic encephalopathy (DEE) in which drug resistance to antiepileptic drugs (AEDs) is common. Focal-onset seizures (FOS) are among the seizure types characterizing LGS. Cenobamate (CNB) is a new AED indicated for the treatment of FOS and it has shown promising results in terms of seizure frequency reduction in both clinical trials and real-world experience. To date, the use of CNB in patients with DEEs is limited to Dravet syndrome. Methods: This was a retrospective study aimed to determine the 12-month effectiveness and tolerability of CNB in patients with LGS following real-world practice. Results: Four patients with LGS receiving CNB treatment were identified. At 12 months from starting CNB, the reduction in baseline seizure frequency ranged from 25 to 74%, with two patients achieving ≥50% seizure reduction. CNB was generally well tolerated and adjustments in doses of concomitant AEDs were required. Conclusions: CNB may represent a promising therapeutic option in patients with drug-resistant epilepsy associated with LGS. Further research is needed to confirm this preliminary evidence.