Hyperkinetic Seizures Research Articles

Characteristics of motion signal profiles of tonic-clonic, tonic, hyperkinetic, and motor seizures extracted from nocturnal video recordings.

In this study, characteristics of signal profiles formed by motion, oscillation, and sound signals were analyzed to evaluate generalizability and variability in a single patient setting (intra-patient variability) and between patients (inter-patient variability). As a secondary objective, the effect of brivaracetam intervention on signal profiles was explored. Patient data included 13 hyperkinetic seizures, 65 tonic seizures, 13 tonic-clonic seizures, and 138 motor seizures from 11 patients. All patients underwent an 8-week monitoring, and after a 3-week baseline, brivaracetam was initiated. Motion, oscillation, and sound features extracted from the video were used to form signal profiles. Variance of signals was calculated, and combined median and quartile visualizations were used to visualize the results. Similarly, the effect of intervention was visualized. Hyperkinetic motion signals showed a rapid increase in motion and sound signals without oscillations and achieved low intra-patient variance. Tonic component created a recognizable peak in motion signal typical for tonic and tonic-clonic seizures. For tonic seizures, inter-patient variance was low. Motor signal profiles were varying, and they did not form a generalizable signal profile. Visually recognizable changes were observed in the signal profiles of two patients. Video-based motion signal analysis enabled the extraction of motion features characteristic for different motor seizure types which might be useful in further development of this system. Tonic component formed a recognizable seizure signature in the motion signal. Hyperkinetic and motor seizures may have not only significantly different motion signal amplitude but also overlapping signal profile characteristics which might hamper their automatic differentiation. Motion signals might be useful in the assessment of movement intensity changes to evaluate the treatment effect. Further research is needed to test generalizability and to increase reliability of the results.

Interictal Electroencephalography and Functional Magnetic Resonance Imaging Reveals Involvement of Mesial Anterior Frontal Structures in Patients With Hyperkinetic Semiology Type I.

This work investigates the presence of common anatomic regions associated with interictal activity in patients with hyperkinetic seizures type I by means of concurrent electroencephalography and functional magnetic resonance imaging. Six patients with hyperkinetic seizures type I were evaluated with video-EEG and electroencephalography and functional magnetic resonance imaging in the context of their presurgical evaluation. Statistical Parametric Mapping was used to perform a correlation study between the occurrence of interictal spikes on EEG and suprathreshold blood oxygen level-dependent changes in the whole-brain volume. In all patients, Statistical Parametric Mapping revealed suprathreshold blood oxygen level-dependent clusters in the mesial anterior frontal areas, including the rostral mesial superior frontal gyrus and the anterior cingulate, associated with the patients' typical interictal activity. The electroencephalography and functional magnetic resonance imaging findings contribute to our understanding of hyperkinetic seizures type I semiology generation and can inform stereo-EEG targeting for surgical planning in refractory cases.

Seizure and movement disorder in CACNA1E developmental and epileptic encephalopathy: Two sides of the same coin or same side of two different coins?

Pathogenic variants in CACNA1E are 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 CACNA1E variant 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) CACNA1E variant. 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.

Characterizing Frontal Lobe Seizure Semiology in Children.

The objective was to analyze seizure semiology in pediatric frontal lobe epilepsy patients, considering age, to localize the seizure onset zone for surgical resection in focal epilepsy. Fifty patients were identified retrospectively, who achieved seizure freedom after frontal lobe resective surgery at Great Ormond Street Hospital. Video-electroencephalography recordings of preoperative ictal seizure semiology were analyzed, stratifying the data based on resection region (mesial or lateral frontal lobe) and age at surgery (≤4 vs >4). Pediatric frontal lobe epilepsy is characterized by frequent, short, complex seizures, similar to adult cohorts. Children with mesial onset had higher occurrence of head deviation (either direction: 55.6% vs 17.4%; p = 0.02) and contralateral head deviation (22.2% vs 0.0%; p = 0.03), ictal body-turning (55.6% vs 13.0%; p = 0.006; ipsilateral: 55.6% vs 4.3%; p = 0.0003), and complex motor signs (88.9% vs 56.5%; p = 0.037). Both age groups (≤4 and >4 years) showed hyperkinetic features (21.1% vs 32.1%), contrary to previous reports. The very young group showed more myoclonic (36.8% vs 3.6%; p = 0.005) and hypomotor features (31.6% vs 0.0%; p = 0.003), and fewer behavioral features (36.8% vs 71.4%; p = 0.03) and reduced responsiveness (31.6% vs 78.6%; p = 0.002). This study presents the most extensive semiological analysis of children with confirmed frontal lobe epilepsy. It identifies semiological features that aid in differentiating between mesial and lateral onset. Despite age-dependent differences, typical frontal lobe features, including hyperkinetic seizures, are observed even in very young children. A better understanding of pediatric seizure semiology may enhance the accuracy of onset identification, and enable earlier presurgical evaluation, improving postsurgical outcomes. ANN NEUROL 2024;95:1138-1148.

Generation of an induced pluripotent stem cell line GWCMCi006-A from a patient with autosomal dominant neurodevelopmental disorder with or without hyperkinetic movements and seizures harboring GRIN1 c.389A > G mutation

Autosomal dominant neurodevelopmental disorder with or without hyperkinetic movements and seizures (NDHMSD) is a rare neurological disorder characterized by neurodevelopmental disorder and hyperkinetic movement, with or without seizures. Heterozygous mutation in the GRIN1 encoding the subunit 1 of the N-methyl-D-aspartate receptor caused this disorder. We first established an induced pluripotent stem cell (iPSC) line from a male patient with c.389A > G mutation in the GRIN1, via reprogramming with KLF4, SOX2, OCT3/4, and c-MYC. Through identification examination, the iPSCs (GWCMCi006-A) stably expressed pluripotency-associated stem cell markers, maintained a normal karyotype, and showed proliferative potential for three-germ layers differentiation.

Automatic classification of hyperkinetic, tonic, and tonic-clonic seizures using unsupervised clustering of video signals.

This study evaluated the accuracy of motion signals extracted from video monitoring data to differentiate epileptic motor seizures in patients with drug-resistant epilepsy. 3D near-infrared video was recorded by the Nelli® seizure monitoring system (Tampere, Finland). 10 patients with 130 seizures were included in the training dataset, and 17 different patients with 98 seizures formed the testing dataset. Only seizures with unequivocal hyperkinetic, tonic, and tonic-clonic semiology were included. Motion features from the catch22 feature collection extracted from video were explored to transform the patients' videos into numerical time series for clustering and visualization. Changes in feature generation provided incremental discrimination power to differentiate between hyperkinetic, tonic, and tonic-clonic seizures. Temporal motion features showed the best results in the unsupervised clustering analysis. Using these features, the system differentiated hyperkinetic, tonic and tonic-clonic seizures with 91, 88, and 45% accuracy after 100 cross-validation runs, respectively. F1-scores were 93, 90, and 37%, respectively. Overall accuracy and f1-score were 74%. The selected features of motion distinguished semiological differences within epileptic seizure types, enabling seizure classification to distinct motor seizure types. Further studies are needed with a larger dataset and additional seizure types. These results indicate the potential of video-based hybrid seizure monitoring systems to facilitate seizure classification improving the algorithmic processing and thus streamlining the clinical workflow for human annotators in hybrid (algorithmic-human) seizure monitoring systems.

Oculogyric crisis induced by risperidone in a child withGRIN1variant

The GluN1 subunit of the N-methyl-d-aspartate (NMDA) receptor is encoded by GRIN1 gene. Mutations in this gene can cause neurodevelopmental disorders with or without hyperkinetic movements and seizures. It can be inherited as either autosomal dominant (NDHMSD) or autosomal recessive (NDHMSR). Patients can present with severe psychomotor delay, seizures, behavioral problems, stereotypies, and oculogyric crisis (OGC). There is emerging evidence regarding the molecular interaction between dopamine and NMDA receptors, cross-talk between dopamine and glutamate signaling, and mutations in GRIN1 could affect both glutamatergic and dopaminergic synaptic transmission. Dopamine antagonists, such as risperidone, which is used to treat behavioral problems, can cause extrapyramidal side effects, including OGC. Here, we present a case of an 8-year-old boy with a GRIN1 variant who was treated with risperidone for severe behavioral problems and experienced an OGC for approximately 30 h. The child had no prior history of such event and experienced no re-occurrences after discontinuing risperidone. This case highlights the importance of exercising extra caution while prescribing dopamine antagonists for patients with GRIN1 mutations and reports the efficacy of memantine in treating seizures and behavioral side effects in such patients. In the era of precision medicine, this case represents a good example of how patient's genetic makeup should be considered in prescribing the right medication for the right patient.

Chapter 15 - Motor seizure semiology

Motor semiology is a major component of epilepsy evaluation, which provides essential information on seizure classification and helps in seizure localization. The typical motor seizures include tonic, clonic, tonic-clonic, myoclonic, atonic, epileptic spasms, automatisms, and hyperkinetic seizures. Compared to the "positive" motor signs, negative motor phenomena, for example, atonic seizures and Todd's paralysis are also crucial in seizure analysis. Several motor signs, for example, version, unilateral dystonia, figure 4 sign, M2e sign, and asymmetric clonic ending, are commonly observed and have significant clinical value in seizure localization. The purpose of this chapter is to review the localization value and pathophysiology associated with the well-defined motor seizure semiology using updated knowledge from intracranial electroencephalographic recordings, particularly stereoelectroencephalography.

Exome Sequencing in an ADSHE Family: VUS Identification and Limits.

Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is the familial form of a focal epilepsy characterized by hyperkinetic focal seizures, mainly arising during non-rapid eye movements (NREM) sleep. Mutations associated with ADSHE account for a small proportion of the genetically determined cases, suggesting the existence of other disease-causing genes. Here, we reported the results obtained by performing trio-based whole-exome sequencing (WES) in an Italian family showing ADSHE and investigated the structural impact of putative variants by in silico modeling analysis. We identified a p.(Trp276Gly) variant in MOXD1 gene encoding the monooxigenase DBH like 1 protein, cosegregating with the disease and annotated as VUS under the ACMG recommendations. Structural bioinformatic analysis predicted a high destabilizing effect of this variant, due to the loss of important hydrophilic bonds and an expansion of cavity volume in the protein hydrophobic core. Although our data support a functional effect of the p.(Trp276Gly) variant, we highlight the need to identify additional families carrying MOXD1 mutations or functional analyses in suitable models to clarify its role in ADSHE pathogenesis. Moreover, we discuss the importance of VUS reporting due to the low rate of pathogenic variant identification by NGS in epilepsy and for future reinterpretation studies.

Automated video analysis of emotion and dystonia in epileptic seizures

ObjectiveTo investigate the accuracy of deep learning methods applied to seizure video data, in discriminating individual semiologic features of dystonia and emotion in epileptic seizures. MethodsA dataset of epileptic seizure videos was used from patients explored with stereo-EEG for focal pharmacoresistant epilepsy. All patients had hyperkinetic (HKN) seizures according to ILAE definition. Presence or absence of (1) dystonia and (2) emotional features in each seizure was documented by an experienced clinician. A deep learning multi-stream model with appearance and skeletal keypoints, face and body information, using graph convolutional neural networks, was used to test discrimination of dystonia and emotion. Classification accuracy was assessed using a leave-one-subject-out analysis. ResultsWe studied 38 HKN seizure videos in 19 patients. By visual analysis based on ILAE criteria, 9/19 patients were considered to have dystonia and 9/19 patients were considered to have emotional signs. Two patients had both dystonia and emotional signs. Applying the deep learning multistream model, spatiotemporal features of facial appearance showed best accuracy for emotion detection (F1 score 0.84), while skeletal keypoint detection performed best for dystonia (F1 score 0.83). SignificanceHere, we investigated deep learning of video data for analyzing individual semiologic features of dystonia and emotion in hyperkinetic seizures. Automated classification of individual semiologic features is possible and merits further study.

Heterogeneity of patients with functional/dissociative seizures: Three multidimensional profiles.

Current concepts highlight the neurological and psychological heterogeneity of functional/dissociative seizures (FDS). However, it remains uncertain whether it is possible to distinguish between a limited number of subtypes of FDS disorders. We aimed to identify profiles of distinct FDS subtypes by cluster analysis of a multidimensional dataset without any a priori hypothesis. We conducted an exploratory, prospective multicenter study of 169 patients with FDS. We collected biographical, trauma (childhood and adulthood traumatic experiences), semiological (seizure characteristics), and psychopathological data (psychiatric comorbidities, dissociation, and alexithymia) through psychiatric interviews and standardized scales. Clusters were identified by the Partitioning Around Medoids method. The similarity of patients was computed using Gower distance. The clusters were compared using analysis of variance, chi-squared, or Fisher exact tests. Three patient clusters were identified in this exploratory, hypothesis-generating study and named on the basis of their most prominent characteristics: A "No/Single Trauma" group (31.4%), with more male patients, intellectual disabilities, and nonhyperkinetic seizures, and a low level of psychopathology; A "Cumulative Lifetime Traumas" group (42.6%), with clear female predominance, hyperkinetic seizures, relatively common comorbid epilepsy, and a high level of psychopathology; and A "Childhood Traumas" group (26%), commonly with comorbid epilepsy, history of childhood sexual abuse (75%), and posttraumatic stress disorder, but also with a high level of anxiety and dissociation. Although our cluster analysis was undertaken without any a priori hypothesis, the nature of the trauma history emerged as the most important differentiator between three common FDS disorder subtypes. This subdifferentiation of FDS disorders may facilitate the development of more specific therapeutic programs for each patient profile.

Predictors of hyperkinetic seizures

ObjectiveTo identify predisposing factors for hyperkinetic seizure occurrence in a representative cohort of surgically treated patients with drug-resistant focal epilepsy. MethodsWe retrospectively recruited all seizure-free patients after epilepsy surgery with a postoperative follow-up ≥12 months. Patients were classified as presenting with hyperkinetic seizures if at least 2 episodes occurred during their disease history, based on clear-cut anamnestic description and/or video-EEG/stereo-EEG recordings. We performed univariable and multivariable logistic regression models to study the association between the occurrence of hyperkinetic seizures and some predictors. ResultsFrom a pool of 1758 consecutive patients who underwent surgery from 1996 to 2017, we identified 974 seizure-free cases. Considering at least 1-year follow-up, 937 cases were included (511 males, 91 patients with hyperkinetic seizures). Variables significantly associated with an increased risk of hyperkinetic seizure occurrence were (1) presence of epilepsy with sleep-related seizures (SRE) (P < 0.001); (2) histological diagnosis of type II focal cortical dysplasia (FCD) (P < 0.001); (3) resection including the frontal lobe (P = 0.002) (4) duration of epilepsy at surgery (P < 0.001) and (5) high seizure frequency at surgery (weekly: P = 0.02 – daily: P = 0.05). A resection including the occipital lobe reduced the risk of hyperkinetic seizures (P = 0.05). About 63% of patients had hyperkinetic seizure onset before 12 years and it was rarely reported before 5 years of age. SignificanceOur findings underlie the role of SRE, type II FCD and frontal epileptogenic zone as predictors of hyperkinetic seizure occurrence and highlight an age-dependent effect in favoring hyperkinetic manifestations.

Sleep-related hypermotor epilepsy with genetic diagnosis: description of a case series in a tertiary referral hospital.

IntroductionSleep-related hypermotor epilepsy (SHE) is characterized by asymmetric tonic/dystonic posturing and/or complex hyperkinetic seizures occurring mostly during sleep. Experts agree that SHE should be considered a unique syndrome.PURPOSEWe present 8 cases of SHE for which a genetic diagnosis was carried out using a multigene epilepsy panel.MethodsWe retrospectively screened familial and isolated cases of SHE in current follow-ups in our center.ResultsWe included 8 (5F/3M) patients, 5 of whom had a positive familial history of epilepsy. We identified a pathogenic mutation in CHRNA4, CHRNB2, and 3 different pathogenic changes in DEPDC5.ConclusionsAwareness of SHE needs to be raised, given its implications for finding an appropriate treatment, its relationship to cognitive and psychiatric comorbidities, and the opportunity to prevent the disorder in the descendants. We present our series with their clinical, radiological, electroencephalographic, and genetic characteristics, in which we found 3 pathogenic mutations in the DEPDC5 gene but not previously reported in the literature. Identifying new pathogenic mutations or new genes responsible for SHE will facilitate a better understanding of the disease and a correct genetic counseling.

Cortical regions and networks of hyperkinetic seizures: Electrocorticography and diffusion tensor imaging study

ObjectiveThe present study investigated the cortical areas and networks responsible for hyperkinetic seizures by analyzing invasive recordings and diffusion tensor imaging (DTI) tractography. MethodsSeven patients with intractable focal epilepsy in whom hyperkinetic seizures were recorded during an invasive evaluation at Sapporo Medical University between January 2012 and March 2020 were enrolled in the present study. Intracranial recordings were analyzed to localize seizure-onset zones (SOZs) and symptomatogenic zones (spread areas at clinical onset). DTI was used to identify the subcortical fibers originating from SOZs. ResultsTen SOZs were located in four areas: (1) the inferior parietal lobule (two SOZs in two patients), (2) temporo-occipital junction (three SOZs in two patients), (3) medial temporal area (three SOZs in three patients) and (4) medial/lateral frontal lobe (two SOZs in two patients). Symptomatogenic zones appeared to be the premotor area, basal temporal area, temporo-occipital junction, and the postcentral gyrus/supramarginal gyrus. The tractographic analysis revealed that the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), middle longitudinal fasciculus (MLF), arcuate fasciculus (AF)/superior longitudinal fasciculus (SLF) II, III, and cingulum bundle may be associated with hyperkinetic seizures. ConclusionThe present results suggest the cortical areas (the inferior parietal lobule, temporo-occipital junction, medial temporal area, and medial/lateral frontal lobe) and subcortical fibers (IFOF, ILF, MLF, AF/SLFII, III, and the cingulum bundle) responsible for generating hyperkinetic seizures.

Clinical characteristics and postoperative seizure outcome in patients with mild malformation of cortical development and oligodendroglial hyperplasia.

We describe for the first time clinical characteristics in a series of 20 pre-surgically investigated patients with mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE) who were operated on in our epilepsy center. We aimed to better diagnose this entity and help surgical planning. Data on 20 patients with histologically confirmed MOGHE were retrospectively evaluated as to age at epilepsy onset and operation, seizure semiology, magnetic resonance imaging (MRI) localization, electroencephalography (EEG) patterns, extent of the operative resection, and postoperative seizure outcome. Epilepsy began mainly in early childhood; however, symptoms did not manifest until adolescence or adulthood in 30% of patients. All patients had pathologic MRI findings. In 45% of patients the lesion was initially overlooked. Most commonly, the lesion was seen in the frontal lobe. Seizure semiology was characterized as follows: (1) epileptic spasms at epilepsy onset were common and (2) nocturnal hyperkinetic seizures during the course of the disease were rare. EEG always showed frequent interictal epileptic discharges. Two peculiar patterns were observed: (1) during sleep stage I-II, sub-continuous repetitive (0.5-1.5/s) unilateral plump spike/polyspike slow waves were seen and (2) during wakefulness, unilateral paroxysms of 2-2.5/s spike-wave complexes occurred. In total, 60% of patients were seizure-free 1year postoperatively. Postoperative seizure outcome was positively correlated with the extent of resection, age at epilepsy onset, and age at operation. Postoperative long-term outcomes remained stable in patients undergoing larger operations. MRI, EEG, and semiology already contribute to the diagnosis of probable MOGHE preoperatively. Because postoperative seizure outcomes depend on the extent of the resection, prior knowledge of a probable MOGHE helps to plan the resection and balance the risks and benefits of such an intervention. In patients undergoing larger operations, epilepsy surgery achieved good postoperative results; the first long-term outcome data were stable in these patients.

Erratum

EpilepsiaVolume 62, Issue 11 p. 2881-2881 ERRATUMFree Access Erratum This article corrects the following: Automated video-based detection of nocturnal motor seizures in children Anouk van Westrhenen, George Petkov, Stiliyan N. Kalitzin, Richard H. C. Lazeron, Roland D. Thijs, Volume 61Issue S1Epilepsia pages: S36-S40 First Published online: May 7, 2020 First published: 15 September 2021 https://doi.org/10.1111/epi.17056AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat In the article by van Westrhenen,1 an inconsistency between the most recent results and those provided in the article as a miscalculation in the data analysis for one of the subjects was found by the authors. As a result, all results of the included cases were re-checked, and it was determined misleading outcomes were provided for six of the 22 subjects reported because a discordant standard was used. Results for the remaining sixteen are unchanged. Once the proper standard is used, a lower number of true positives and a higher number of false alarms are seen. The number of false alarms is 87 rather than 81. Consequently, the overall sensitivity of the video algorithm for the detection of convulsive seizures is 78% rather than the 94% reported. The detection performance for non-convulsive seizures was also affected: overall sensitivity for detecting hyperkinetic seizures 73% rather than the 100% reported. These are the corrected results: The video algorithm detected 54 out of 69 convulsive seizures occurring in six children (median sensitivity per participant 54% [range 0%–100%]; overall sensitivity 78% [95% CI 57.5–100%]; F1-score = 0.51). The algorithm also detected 117 of 161 hyperkinetic seizures (mean sensitivity 86% [range 72%-100%]; overall sensitivity 73%) occurring in two children. 87 False alarms occurred in seven children (median FAR 0 per participant per night [range 0–0.53]; overall FAR 0.05/night). 58% of false alarms were behaviour-related (awake and playing in the bed). A corrected version of Figure 1 follows. We apologize for these errors. REFERENCE 1van Westrhenen A, Petkov G, Kalitzin SN, Lazeron RHC, Thijs RD. Automated video-based detection of nocturnal motor seizures in children. Epilepsia. 2020; 61(S1): S36– 40. 10.1111/epi.16504PubMedWeb of Science®Google Scholar Volume62, Issue11November 2021Pages 2881-2881 ReferencesRelatedInformation

Neural networks underlying hyperkinetic seizures: A quantitative PET and SEEG study

ObjectiveHyperkinetic seizures (HKS) are characterized by complex movements that commonly occur during seizures arising from diverse cortical structures. A common semiology network may exist and analyzing the anatomo-electrical mechanisms would facilitate presurgical evaluation. Here, quantitative positron emission tomography (PET) and stereoelectroencephalography (SEEG) analysis was used to explore the underlying mechanism of HKS. MethodsWe retrospectively collected patients with epilepsy with HKS between 2014 and 2019. The interictal PET data of patients with epilepsy with HKS were compared with those of 25 healthy subjects using statistical parametric mapping to identify regions with significant hypometabolism. Then, regions of interest (ROI) for SEEG analysis were identified based on the results of PET analysis. Patients in which the ROIs were covered by intracerebral electrodes were selected for further analysis. Stereoelectroencephalography –clinical correlations with latency measurements were analyzed, and we also performed coherence analysis among ROIs both before and during HKS. ResultsBased on the inclusion criteria, 27 patients were analyzed. In the PET analysis, significant hypometabolism was observed in the ipsilateral dorsoanterior insular lobe, bilateral mesial frontal lobes (supplementary motor area/middle cingulate cortex, SMA/MCC), and the bilateral heads of the caudate nuclei in patients with HKS compared with the control group (p < 0.001). We selected dorsoanterior insula and SMA/MCC as ROIs for SEEG analysis. Eight patients with 23 HKS events were selected for further analysis. There was a linear correlation between the ictal involvement of both the dorsoanterior insula and SMA/MCC with the onset of HKS. Stereoelectroencephalography analysis indicated alpha range activity seemed more often associated with dorsoanterior insula and SMA/MCC involvement during HKS. ConclusionsThe dorsoanterior insular lobe, mesial frontal lobes (SMA/MCC), and the bilateral heads of the caudate nuclei were probably involved in the generation of HKS. The SEEG analysis further indicated that the occurrence of HKS might be partly associated with synchronized rhythmical alpha activity between dorsoanterior insula and SMA/MCC.

Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy: Pathophysiology and Pharmacology.

Sleep-related hypermotor epilepsy (SHE) is characterized by hyperkinetic focal seizures, mainly arising in the neocortex during non-rapid eye movements (NREM) sleep. The familial form is autosomal dominant SHE (ADSHE), which can be caused by mutations in genes encoding subunits of the neuronal nicotinic acetylcholine receptor (nAChR), Na+-gated K+ channels, as well as non-channel signaling proteins, such as components of the gap activity toward rags 1 (GATOR1) macromolecular complex. The causative genes may have different roles in developing and mature brains. Under this respect, nicotinic receptors are paradigmatic, as different pathophysiological roles are exerted by distinct nAChR subunits in adult and developing brains. The widest evidence concerns α4 and β2 subunits. These participate in heteromeric nAChRs that are major modulators of excitability in mature neocortical circuits as well as regulate postnatal synaptogenesis. However, growing evidence implicates mutant α2 subunits in ADSHE, which poses interpretive difficulties as very little is known about the function of α2-containing (α2*) nAChRs in the human brain. Planning rational therapy must consider that pharmacological treatment could have different effects on synaptic maturation and adult excitability. We discuss recent attempts towards precision medicine in the mature brain and possible approaches to target developmental stages. These issues have general relevance in epilepsy treatment, as the pathogenesis of genetic epilepsies is increasingly recognized to involve developmental alterations.

Temporal pole epilepsy surgery-Sparing the hippocampus.

Temporal pole epilepsy (TPE) is a poorly known and difficult to individualize subtype of temporal lobe epilepsy. Consequently, in drug-resistant TPE, there is still a debate on the need for a large surgical removal of the temporal pole and mesial temporal structures or a limited resection of the temporal pole. We reviewed all patients who underwent presurgical evaluation for drug-resistant epilepsy over a 17-year period, and report here 19 patients with proven drug-resistant temporal pole epilepsy who underwent a selective temporal pole resection with respect to mesial structures. Most (15) TPE patients exhibited seizures resembling mesiotemporal seizures, whereas the others exhibited nocturnal hyperkinetic seizures or an association of both seizure types. MRI revealed a temporal pole lesion in 58% of patients. Long-term postoperative outcome after a conservative surgery was excellent: 63% of patients were seizure-free (International League Against Epilepsy [ILAE] 1) at 1-year postsurgery and 78% at 5years. These results show that TPE has no specific electroclinical features but is a distinct type of temporal lobe epilepsy allowing a conservative surgery. Respecting the mesiotemporal structures is a valid surgical approach for drug-resistant temporal pole epilepsy.

Seizures with paroxysmal arousals in sleep-related hypermotor epilepsy (SHE): Dissecting epilepsy from NREM parasomnias.

Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy characterized by seizures occurring mostly during sleep, ranging from brief seizures with paroxysmal arousals (SPAs) to hyperkinetic seizures and ambulatory behaviors. SPAs are brief and stereotypic seizures representing the beginning of a major seizure. Distinguishing SPAs from disorders of arousal (DOAs) and their briefest episodes called simple arousal movements (SAMs) is difficult. We performed a characterization of SPAs and SAMs to identify video-polysomnographic (VPSG) features that can contribute to the diagnosis of SHE or DOA. Fifteen SHE, 30 DOA adult patients, and 15 healthy subjects underwent full-night VPSG. Two neurologist experts in sleep disorders and epilepsy classified all the sleep-related movements and episodes recorded. For each SPAs and SAMs, sleep stage at onset, duration, limb involvement, progression, and semiology have been identified. A total of 121 SPAs were recorded, emerging mostly during stage 1-2 non-rapid eye movement (NREM) sleep (median duration: 5seconds). At the beginning, the SPAs motor pattern was hyperkinetic in 78 cases (64%), involving more than three non-contiguous or all body parts. The standard was a constant progression of movements during SPAs without any motor arrests. In DOA patients a total of 140 SAMs were recorded (median duration: 12seconds) mostly emerging during stage 3 NREM sleep. In SAMs, we did not observe any tonic/dystonic or hypermotor patterns or stereotypy; motor arrest was present over the course of about half of the episodes. In comparison with both DOA and healthy subjects, SHE patients showed a higher number of sleep-related movements per night and a reduction of sleep efficiency. SPAs and SAMs present different semiological and clinical features. Their recognition could be useful to drive the diagnosis when major episodes are not recorded during VPSG in patients with a clear clinical history of SHE or DOA.