IMPORTANCE Stereoelectroencephalography (SEEG) has become the criterion standard in case of inconclusive noninvasive presurgical epilepsy workup. However, up to 40% of patients are subsequently not offered surgery because the seizure-onset zone is less focal than expected or cannot be identified.OBJECTIVE To predict focality of the seizure-onset zone in SEEG, the 5-point 5-SENSE score was developed and validated. DESIGN, SETTING, AND PARTICIPANTS This was a monocentric cohort study for score development followed by multicenter validation with patient selection intervals between February 2002 to October 2018 and May 2002 to December 2019. The minimum follow-up period was 1 year. Patients with drug-resistant epilepsy undergoing SEEG at the Montreal Neurological Institute were analyzed to identify a focal seizure-onset zone. Selection criteria were 2 or more seizures in electroencephalography and availability of complete neuropsychological and neuroimaging data sets. For validation, patients from 9 epilepsy centers meeting these criteria were included. Analysis took place between May and July 2021. MAIN OUTCOMES AND MEASURES Based on SEEG, patients were grouped as focal and nonfocal seizure-onset zone. Demographic, clinical, electroencephalography, neuroimaging, and neuropsychology data were analyzed, and a multiple logistic regression model for developing a score to predict SEEG focality was created and validated in an independent sample. RESULTS A total of 128 patients (57 women [44.5%]; median [range] age, 31 [13-58] years) were analyzed for score development and 207 patients (97 women [46.9%]; median [range] age , 32 [16-70] years) were analyzed for validation. The score comprised the following 5 predictive variables: focal lesion on structural magnetic resonance imaging, absence of bilateral independent spikes in scalp electroencephalography, localizing neuropsychological deficit, strongly localizing semiology, and regional ictal scalp electroencephalography onset. The 5-SENSE score had an optimal mean (SD) probability cutoff for identifying a focal seizure-onset zone of 37.6 (3.5). Area under the curve, specificity, and sensitivity were 0.83, 76.3% (95% CI, 66.7-85.8), and 83.3% (95% CI, 72.30-94.1), respectively. Validation showed 76.0% (95% CI, 67.5-84.0) specificity and 52.3% (95% CI, 43.0-61.5) sensitivity. CONCLUSIONS AND RELEVANCEHigh specificity in score development and validation confirms that the 5-SENSE score predicts patients where SEEG is unlikely to identify a focal seizure-onset zone. It is a simple and useful tool for assisting clinicians to reduce unnecessary invasive diagnostic burden on patients and overutilization of limited health care resources.

ObjectivesNew-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.Case descriptionIn 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.ConclusionThis 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.

Objectives. To investigate the effectiveness, safety, and tolerability of perampanel (PER) when used as monotherapy to treat focal or generalized epilepsy in everyday clinical practice, using data from the PERMIT study. Methods. PERMIT was a pooled analysis of 44 real-world studies from 17 countries, in which people with focal and generalized epilepsy were treated with PER. This post hoc analysis included people with epilepsy (PWE) from PERMIT who were treated with PER monotherapy at baseline. Retention and effectiveness were assessed after 3, 6, and 12 months. Effectiveness assessments included ≥50% responder rate and seizure freedom rate (no seizures since at least the prior visit). Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. Results. Overall, 268 PWE were treated with PER monotherapy at baseline. Retention was assessed for 168 PWE, effectiveness for 183 PWE, and safety and tolerability for 197 PWE. Retention rates were 91.1%, 87.3%, and 73.3% at 3, 6, and 12 months, respectively. At 12 months, responder rates were 84.2% overall, 82.9% in PWE with only focal-onset seizures at baseline, and 88.0% in those with only generalized-onset seizures at baseline; corresponding freedom rates were 62.9%, 57.7%, and 80.0%, respectively. AEs were reported for 45.2% of PWE. The most frequently reported AEs (≥5% of PWE) were dizziness/vertigo (16.8%), irritability (11.2%), somnolence (9.1%), and depression (6.6%). Over 12 months, 13.7% discontinued due to AEs. Conclusions. PER was effective when used as monotherapy in clinical practice, particularly in those with generalized-onset seizures, and was generally well tolerated.