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Pathogenic variants in CACNA1Eare associated with early‐onset epileptic and developmental encephalopathy (DEE). Severe to profound global developmental delay, early‐onset refractory seizures, severe hypotonia, and macrocephaly are the main clinical features. Patients harboring the recurrent CACNA1Evariant p.(Gly352Arg) typically present with the combination of early‐onset DEE, dystonia/dyskinesia, and contractures. We describe a 2‐year‐and‐11‐month‐old girl carrying the p.(Gly352Arg) CACNA1Evariant. She has a severe DEE with very frequent drug‐resistant seizures, profound hypotonia, and episodes of dystonia and dyskinesia. Long‐term video‐EEG‐monitoring documented subsequent tonic asymmetric seizures during wakefulness and mild paroxysmal dyskinesias of the trunk out of sleep which were thought to be a movement disorder and instead turned out to be focal hyperkinetic seizures. This is the first documented description of the EEG findings in this disorder. Our report highlights a possible overlap between cortical and subcortical phenomena in CACNA1E‐DEE. We also underline how a careful electro‐clinical evaluation might be necessary for a correct discernment between the two disorders, playing a fundamental role in the clinical assessment and proper management of children with CACNA1E‐DEE. Content available: Video

Recording seizures on video‐EEG has a high diagnostic value. However, bilateral convulsive seizures constitute a risk for the patients. Our aim was to investigate the diagnostic yield and associated risks of provocation methods in short‐term video‐EEGs. We extracted data on seizures and provocation methods from a large database of short‐term video‐EEGs with standardized annotations using SCORE (Standardized Computer‐based Organized reporting of EEG). 2742 paroxysmal clinical episodes were recorded in 11 919 consecutive EEGs. Most epileptic seizures (54%) were provoked. Hyperventilation provoked most of typical absence seizures (55%), intermittent photic stimulation (IPS) provoked myoclonic seizures (25%) and most of bilateral convulsive seizures (55%), while 43% of focal seizures were precipitated by sleep. All but one of the 16 bilateral convulsive seizures were provoked by IPS or sleep. Latency between start of generalized photoparoxysmal EEG response and bilateral convulsive seizures were ≤3 s in all but one patient. The large, structured database provides evidence for the diagnostic utility of various provocation methods in short‐term video‐EEGs. The risk of bilateral convulsive seizures is relatively small, but it cannot be prevented by stopping IPS after 3 s. A priori knowledge about seizure semiology helps planning patient‐tailored provocation strategy in short‐term video‐EEGs.

Pathogenic variants in SCN8Aare associated with a broad phenotypic spectrum, including Self‐Limiting Familial Infantile Epilepsy (SeLFIE), characterized by infancy‐onset age‐related seizures with normal development and cognition. Movement disorders, particularly paroxysmal kinesigenic dyskinesia typically arising after puberty, may represent another core symptom. We present the case of a 1‐year‐old girl with a familial disposition to self‐limiting focal seizures from the maternal side and early‐onset orofacial movement disorders associated with SCN8A‐SeLFIE. Brain MRI was normal. Genetic testing revealed a maternally inherited SCN8Avariant [c.4447G > A; p.(Glu1483Lys)]. After the introduction of valproic acid, she promptly achieved seizure control as well as complete remission of strabismus and a significant decrease in episodes of tongue deviation. Family history, genetic findings, and epilepsy phenotype are consistent with SCN8A‐SeLFIE. Movement disorders are an important part of the SCN8Aphenotypic spectrum, and this case highlights the novel early‐onset orofacial movement disorders associated with this condition. The episodes of tongue deviation and protrusion suggest focal oromandibular (lingual) dystonia. Additionally, while infantile strabismus or esophoria is a common finding in healthy individuals, our case raises the possibility of an ictal origin of the strabismus. This study underscores the importance of recognizing and addressing movement disorders in SCN8A‐SeLFIE patients, particularly the rare early‐onset orofacial manifestations. It adds to the growing body of knowledge regarding the diverse clinical presentations of SCN8A‐associated disorders and suggests potential avenues for clinical management and further research. Content available: Video

IMPORTANCE: Electroencephalograms (EEGs) are a fundamental evaluation in neurology but require special expertise unavailable in many regions of the world. Artificial intelligence (AI) has a potential for addressing these unmet needs. Previous AI models address only limited aspects of EEG interpretation such as distinguishing abnormal from normal or identifying epileptiform activity. A comprehensive, fully automated interpretation of routine EEG based on AI suitable for clinical practice is needed. OBJECTIVE: To develop and validate an AI model (Standardized Computer-based Organized Reporting of EEG–Artificial Intelligence [SCORE-AI]) with the ability to distinguish abnormal from normal EEG recordings and to classify abnormal EEG recordings into categories relevant for clinical decision-making: epileptiform-focal, epileptiform-generalized, nonepileptiform-focal, and nonepileptiform-diffuse. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter diagnostic accuracy study, a convolutional neural network model, SCORE-AI, was developed and validated using EEGs recorded between 2014 and 2020. Data were analyzed from January 17, 2022, until November 14, 2022. A total of 30 493 recordings of patients referred for EEG were included into the development data set annotated by 17 experts. Patients aged more than 3 months and not critically ill were eligible. The SCORE-AI was validated using 3 independent test data sets: a multicenter data set of 100 representative EEGs evaluated by 11 experts, a single-center data set of 9785 EEGs evaluated by 14 experts, and for benchmarking with previously published AI models, a data set of 60 EEGs with external reference standard. No patients who met eligibility criteria were excluded. MAIN OUTCOMES AND MEASURES: Diagnostic accuracy, sensitivity, and specificity compared with the experts and the external reference standard of patients’ habitual clinical episodes obtained during video-EEG recording. RESULTS: The characteristics of the EEG data sets include development data set (N = 30 493; 14 980 men; median age, 25.3 years [95% CI, 1.3-76.2 years]), multicenter test data set (N = 100; 61 men, median age, 25.8 years [95% CI, 4.1-85.5 years]), single-center test data set (N = 9785; 5168 men; median age, 35.4 years [95% CI, 0.6-87.4 years]), and test data set with external reference standard (N = 60; 27 men; median age, 36 years [95% CI, 3-75 years]). The SCORE-AI achieved high accuracy, with an area under the receiver operating characteristic curve between 0.89 and 0.96 for the different categories of EEG abnormalities, and performance similar to human experts. Benchmarking against 3 previously published AI models was limited to comparing detection of epileptiform abnormalities. The accuracy of SCORE-AI (88.3%; 95% CI, 79.2%-94.9%) was significantly higher than the 3 previously published models (P < .001) and similar to human experts. CONCLUSIONS AND RELEVANCE: In this study, SCORE-AI achieved human expert level performance in fully automated interpretation of routine EEGs. Application of SCORE-AI may improve diagnosis and patient care in underserved areas and improve efficiency and consistency in specialized epilepsy centers.

We report the association, not previously described, between trisomy 20/ monosomy 18 and congenital bilateral perisylvian syndrome (CBPS), a condition featuring intellectual disability, epilepsy, oro‐motor dysfunction and bilateral perisylvian polymicrogyria (BPP) in a 29‐year‐old individual. Detailed clinical evaluation, long‐term EEG and EEG analysis by means of electrical source imaging (ESI), 3T MRI and array‐CGH were performed. Clinical examination showed moderate/severe intellectual disability, dysmorphic features, oro‐motor dysfunction, short stature, abnormal hands and feet, bradykinesia and abnormal posture. The patient had suffered from drug‐resistant epilepsy since infancy. Brain MRI showed that BPP was consistent with CBPS. Additional imaging features revealed corpus callosum and cerebellar hypoplasia and fusion of the C1‐C2 vertebrae. Ictal EEG and ESI documented tonic seizures originating from the right polymicrogyric cortex. Facial gestalt included dysmorphic features reported in patients with 18‐ and 20+ chromosomal rearrangements. Array‐CGH showed an unbalanced translocation, arr(18p)x1(20p)x3. In conclusion, we provide a detailed electro‐clinical and MRI description of a novel condition characterized by the association between trisomy 20p/monosomy 18p and CBPS, also illustrating its clinical evolution into adulthood. This information may help paediatricians, neurologists and geneticists to better counsel families about the developmental prognosis of this rare unbalanced chromosomal rearrangement.

Although epilepsy as a comorbidity in neurodegenerative disorders is increasingly recognized, its incidence is still underestimated and the features of epilepsy in the different neurodegenerative conditions are still poorly defined. Improved health care, resulting in increased longevity, will unavoidably lead to an increment of epilepsy cases in the elderly. Thus, it is conceivable to expect that neurologists will have to deal with these comorbid conditions to a growing extent in the future. In this seminar, we provide an updated overview of the clinical features, pathophysiological mechanisms and diagnostic and treatment approaches of epilepsy in the most common neurodegenerative disorders (such as Alzheimer disease and other types of dementia, Parkinson disease, Down syndrome, prion diseases, and progressive myoclonus epilepsies), aiming to provide a tool that can help epileptologists and neurologists in the diagnosis and management of this increasingly reported comorbidity.

Pathogenic variants in GABRB3have been associated with a spectrum of phenotypes from severe developmental disorders and epileptic encephalopathies to milder epilepsy syndromes and mild intellectual disability (ID). In this study, we analyzed a large cohort of individuals with GABRB3variants to deepen the phenotypic understanding and investigate genotype–phenotype correlations.

Objective. Coffin‐Siris syndrome (CSS) is a rare congenital malformation syndrome, caused by mutations in the ARID1Bgene in over half of the cases. While the clinical characteristics of the syndrome have been increasingly described, a detailed evaluation of the epileptic phenotype in patients with ARID1Balterations and CSS has not been approached yet. We report seven patients with ARID1B‐related CSS, focusing on epilepsy and its electroclinical features. Methods. The evolution of epilepsy and EEG findings of children with CSS are described and compared with patients previously reported in the literature. Results. The patients described here reveal common features, consistent with those of patients previously described in the literature. Significance. The epilepsy phenotype of CSS due to ARID1Bpathogenic variants may be described as focal epilepsy with seizures, variable in frequency, arising from motor areas, with onset in the first years of life and susceptibility to fever, and interictal perisylvian (centrotemporal) epileptiform abnormalities that are enhanced during sleep with possible evolution to an EEG pattern of continuous spike and wave during sleep (without documented developmental regression). Additional information emerging from other patients is needed to confirm this definition.

Objective: This study aimed to analyse the effect of neuropsychological activation methods on interictal epileptiform discharges, compared to standard activation methods, for both focal and generalized epilepsies. Methods: This was a multicentre, prospective study including 429 consecutive EEG recordings of individuals with confirmed or suspected diagnosis of epilepsy. Neuropsychological activation included reading aloud in foreign and native language, praxis and a letter cancelation task (each with a duration of three minutes). After counting interictal discharges in three‐minute time windows, activation and inhibition were assessed for each procedure, accounting for spontaneous fluctuations (95% CI) and compared to the baseline condition with eyes closed. Differences between generalized and focal epilepsies were explored. Results: Interictal epileptiform discharges were present in 59.4% of the recordings. Activation was seen during hyperventilation in 31%, in at least one neuropsychological activation method in 15.4%), during intermittent photic simulation in 13.1% and in the resting condition with eyes open in 9.9%. The most frequent single cognitive task eliciting activation was praxis (10.3%). Lasting activation responses were found in 18–25%. Significant inhibition was found in 88/98 patients with baseline interictal epileptiform discharges, and was not task‐specific. Significance: Adding a brief neuropsychological activation protocol to the standard EEG slightly increased its sensitivity in patients with either focal or generalized epilepsy. However, in unselected epilepsy patients, this effect seems only exceptionally to result in ultimate diagnostic gain, compared to standard procedures. From a diagnostic perspective, cognitive tasks should be reserved for patients with a suspicion of cognitive reflex epilepsy/seizures and probably require longer exposure times. Further research is needed to explore potential therapeutic applications of the observed inhibition of interictal epileptiform discharges by cognitive tasks in some patients.

Since its first description, quantifying the burden of epileptiform abnormalities in sleep EEG has played a fundamental role in the diagnosis of Encephalopathy related to Status Epilepticus during slow Sleep (ESES). In fact, in the 1971 seminal paper by Tassinari's group and in the following studies on this syndrome, the amount of epileptiform discharges (EDs) was calculated as the percentage of slow sleep occupied by spike‐and‐waves and referred to as “spike and wave index” (SWI). However, nowadays it is becoming increasingly clear that the SWI alone does not explain the whole clinical course of patients affected by ESES. In this paper, we aim to provide a state‐of‐the‐artsummary of the quantitative EEG methods currently used in the ESES/CSWS literature, highlighting the possible pitfalls and discrepancies explaining the unsatisfactory correlation between SWI and clinical course. Furthermore; we illustrate a number of methodological refinements ‐ taking into account inter‐individual, intra‐individual, and temporal variability of EDs ‐ alongside “new” quantitative variables ‐including ED‐related and sleep‐related features ‐ potentially useful to reach a reliable electro‐clinical correlation in patients with ESES.

Encephalopathy related to Status Epilepticus during slow Sleep (ESES) is a peculiar electro‐clinical condition, with variable etiologies, characterized by an age‐dependent phenomenon of extreme activation of epileptic activity during sleep, i.e. “status epilepticus during sleep”, that is strictly associated with the appearance of cognitive and behavioral disturbances. Even though the peculiar EEG picture is fundamental for the diagnosis of ESES, clear‐cut and shared diagnostic criteria for defining the EEG boundaries of this syndrome are still lacking. The diagnosis of ESES can be further complicated by the variability of the EEG findings, that during the course of the disease can change from diffuse to more or less focal and viceversa, depending both on the spontaneous clinical evolution of this condition and/or on the effects of medications. Given the complexity and the heterogeneity of EEG parameters during the ESES course, it is important to correlate the EEG findings with the concomitant cognitive and behavioral status, possibly taking into account not only the spike‐wave index, but also other parameters, such as for instance the topography of the epileptic abnormalities, their patterns of spread, and their fluctuations over time. Moreover, the epileptiform activity not only during sleep, but also during wakefulness, the presence of focal slowing, the organization of the EEG background and a derangement of the sleep architecture may play a role in determining the clinical picture.

We describe a case of a child suffering from alternating hemiplegia with a heterozygous p. E815K pathogenic variant of ATP1A3. The patient started to present abnormal eye movements in the first days of life, followed by the appearance at 2 months of dystonic episodes, and later on, by recurrent episodes of alternating hemiplegia more often on the right side. A severe epilepsy started at the age of 2 years with episodes of status epilepticus since the onset which frequently recurred, requiring admission to the intensive care unit. MRI showed bilateral mesial temporal sclerosis and a left-sided ischaemic lesion. Interictal EEG showed bilateral abnormalities, whereas postictal EEG after status epilepticus showed overt slowing on the left side, suggesting a predominant involvement of ictal activity of the left hemisphere. We hypothesize that in our patient, the left hemisphere might have been more prominently affected by the pathogenetic abnormalities underlying alternating hemiplegia of childhood, rendering it more prone to early ischaemic lesions and recurrent unilateral status epilepticus. We speculate whether alternating hemiplegia of childhood shares some common pathophysiological mechanisms with familial hemiplegic migraine that may be associated with a pathogenic variant of ATP1A2.

SCN8Aencodes the sodium channel voltage-gated 8-subunit (Nav1.6). SCN8Amutations have recently been associated with epilepsy and neurodevelopmental disorders. We aimed to delineate the phenotype associated with SCN8Amutations.

Patients with Down syndrome are now living longer and the overall prevalence of epilepsy is increasing, however, full characterisation of epilepsy in adult age is still incomplete. We describe the electroclinical characteristics of epilepsy in 22 adult patients with Down syndrome (11 males, 11 females), with a mean age of 46 years (range: 28‐64 years), followed at the Epilepsy Centre, San Paolo Hospital in Milan. Mean age at epilepsy onset was 36.8 years (range: 6‐60 years). Nine out of 22 patients had focal epilepsy, while nine had late‐onset myoclonic epilepsy. In four patients, epilepsy was unclassified. The EEG pattern of our patients was characterised by a progressive slowing of the background activity with sharp‐and‐slow waves with frontal predominance. In the patients diagnosed with late‐onset myoclonic epilepsy, the EEGs showed generalised polyspike waves. Three subjects had an episode of myoclonic status epilepticus at the beginning or in the course of the disorder. After the first descriptions of late‐onset myoclonic epilepsy by Genton and Paglia (1994), this is one of the largest patient cohorts reported. Our data confirm that epilepsy in adult patients with Down syndrome presents peculiar electroclinical characteristics which should be recognized early as prompt, effective treatment may be beneficial. [Published with video sequences]

Patients with Down syndrome are now living longer and the overall prevalence of epilepsy is increasing, however, full characterisation of epilepsy in adult age is still incomplete. We describe the electroclinical characteristics of epilepsy in 22 adult patients with Down syndrome (11 males, 11 females), with a mean age of 46 years (range: 28–64 years), followed at the Epilepsy Centre, San Paolo Hospital in Milan. Mean age at epilepsy onset was 36.8 years (range: 6–60 years). Nine out of 22 patients had focal epilepsy, while nine had late-onset myoclonic epilepsy. In four patients, epilepsy was unclassified. The EEG pattern of our patients was characterised by a progressive slowing of the background activity with sharp-and-slowwaves with frontal predominance. In the patients diagnosed with late-onsetmyoclonic epilepsy, the EEGs showed generalised polyspike waves. Three subjects had an episode ofmyoclonic status epilepticus at the beginning or in the course of the disorder. After the first descriptions of lateonset myoclonic epilepsy by Genton and Paglia (1994), this is one of the largest patient cohorts reported. Our data confirm that epilepsy in adult patients with Down syndrome presents peculiar electroclinical characteristics which should be recognized early as prompt, effective treatment may be beneficial.

We describe the case of an eight‐year‐old boy, who underwent a video‐stereo EEG (SEEG) investigation for the presurgical assessment of drug‐resistant epilepsy, related to a right fronto‐lateral cortical dysplasia and who became seizure‐free after epilepsy surgery. The unexpected finding of the investigations was that intracerebral, high frequency (50 Hz) electrical stimulation (HFS) triggered the emergence of automatic and involuntary forward‐backward locomotion during a focal seizure while the boy was standing. This clinical manifestation was different from the chaotic motor activity described during epileptic wanderings. The stimulation of the same fronto‐lateral region, while the patient was lying, produced only the subjective sensation that the legs were moving, although there was no physical manifestation of this. Human locomotion is an innate motor behavior that is normally due to the activation of the spinal network for locomotion (central pattern generator). The emergence of different stereotyped motor behaviors during focal epileptic seizures or sleep disorders has recently been interpreted as a release of subcortical central pattern generators (Tassinari et al.2005). In view of this, we hypothesize that the involuntary and robot‐like locomotion of our patient could be the ictal expression of the release of subcortical locomotor CPGs. [Published with video sequences] Content available: Video

Charles Bonnet syndrome (CBS) is a disorder characterized by the occurrence of complex visual hallucinations in patients with acquired impairment of vision and without psychiatric disorders. In spite of the high incidence of visual field defects following antero‐mesial temporal lobectomy for refractory temporal lobe epilepsy, reports of CBS in patients who underwent this surgical procedure are surprisingly rare. We describe a patient operated on for drug‐resistant epilepsy. As a result of left antero‐mesial temporal resection, she presented right homonymous hemianopia. A few days after surgery, she started complaining of visual hallucinations, such as static or moving “Lilliputian” human figures, or countryside scenes, restricted to the hemianopic field. The patient was fully aware of their fictitious nature. These disturbances disappeared progressively over a few weeks. The incidence of CBS associated with visual field defects following epilepsy surgery might be underestimated. Patients with post‐surgical CBS should be reassured that it is not an epileptic phenomenon, and that it has a benign, self‐limiting, course which does not usually require treatment.

The aim of this study was to obtain a qualitative and quantitative description of the phenomenon of forced prehension during epileptic seizures (ictal grasping‐ IG) with hyperkinetic semiology. We analysed retrospectively the presurgical, video‐EEG recordings of 35 “frontal hyperkinetic” seizures (FHS) in 14 patients (age range: 9‐48 years) evaluating the features of ictal grasping by means of off‐line, frame‐by‐frame video‐analysis. Ictal grasping was observed in 97.1% of the frontal hyperkinetic seizures in 100% of the patients, with a mean latency of 3.2 seconds with respect to seizure‐onset; a mean number of 7.7 IG per seizure were detected. During the same FHS, both arms could perform IG in an alternating fashion. Grasping was usually preceded by a reaching movement and followed by holding or pulling. The sites of prehension were restricted to relatively few sectors, either on the patient's body (45.5%) or the peri‐personal space (54.5%). In some cases, the grasping was elicited by hand touching. We did not find a consistent relationship between side of hand grasping and side of ictal EEG discharge or MRI lesion. In conclusion, ictal grasping is an extremely frequent clinical manifestation during FHS. It was an early, forced and repetitive motor behavior, without a clear lateralizing value. Ictal grasping appeared with consistent semiological features, similar to voluntary prehension, suggesting a probable ictal release of physiological grasping behavior. [Published with video sequences] Content available: Video

We investigated the electroclinical features of 12 patients with childhood absence epilepsy (CAE), presenting with typical absence seizures associated with myoclonic manifestations of the face or neck. All patients underwent repeated and prolonged split‐screen video‐polygraphic EEG recordings. The polygraphic recordings and clinical correlations of the absence seizures were analysed. All patients presented with multi‐quotidian, typical absence seizures. During the absences, the patients could show mild, rhythmic, myoclonic jerks involving facial areas (eyebrows, nostrils, perioral region, chin) or neck muscles (sternocleidomastoideus), with the same frequency as the spike‐wave complexes. Polygraphic tracings demonstrated that the myoclonias were correlated to the spike component. Clinically, all patients showed a benign course, with complete seizure control under antiepileptic treatment. In the follow‐up, 7 patients withdrew from treatment without relapse. We conclude that all our patients showed an electroclinical picture consistent with CAE. The occurrence of myoclonic manifestations of the face or neck associated with the absences did not influence the benign course of their disease. The electroclinical features observed in our group of patients differentiates our cases both from epilepsy with myoclonic absences and from absences with perioral myoclonia (with Video).