Nonmotor Seizures Research Articles

CASPR2-IgG-associated autoimmune seizures.

This study was undertaken to report clinical presentations and outcomes of CASPR2-IgG-associated seizures. Mayo Clinic Neuroimmunology database was queried to identify CASPR2-IgG-seropositive (CASPR2-IgG+) patients evaluated at our institution (2009-2019). Of the 53 CASPR2-IgG+ patients (titer ≥ 1:10), 20had seizures (38%). All seizure patients were male, with median onset age of 68years. Eighteen (90%) had seizures at initial presentation. One patient was found to have malignancy (colon adenocarcinoma). Two patients had coexisting LGI1-IgG. Twelve patients had archived sera, which on titration had CASPR2-IgG titers ≥ 1:100. Fifteen patients (75%) met criteria for autoimmune encephalitis. Patients most commonly presented with focal onset, nonmotor seizures with impaired awareness (n=14, 70%). Eleven patients also had focal motor and/or sensory seizures as one of the seizure semiologies. The majority of patients (n=11, 55%) developed generalized tonic-clonic seizures during their disease course. Seizure clusters occurred in 12 patients. In addition to seizures, patients developed cognitive disturbance (n=16, 80%), episodic emotional lability (n=13, 65%), paroxysmal dizziness (n=9, 45%), episodic ataxia (n=6, 30%), and chronic ataxia (n=9, 45%). Only three patients (15%) had coexisting peripheral nervous system involvement. Frontotemporal or temporal ictal and/or interictal electroencephalographic abnormalities were present among nine patients, and three had multifocal epileptiform abnormalities. Eight patients (40%) had medial temporal T2/fluid-attenuated inversion recovery hyperintensity on brain magnetic resonance imaging. Elevated cerebrospinal fluid protein and/or lymphocytic pleocytosis was present in most cases (13/14, 93%). Thirteen patients reached seizure freedom following initiation of antiseizure medication (ASM; n=4) or a combination of immunotherapy and ASM (n=9). Median duration of follow-up was 25months (range = 2-136months). CASPR2-IgG evaluation should be considered among older male patients with new onset focal seizures and impaired awareness often occurring in clusters with/without features of encephalitis. Coexisting neurological manifestations, including episodic emotional lability, ataxia, and paroxysmal dizziness, also aid in the diagnosis.

Long-term outcomes of very-low-birth-weight and low-birth-weight preterm newborns with neonatal seizures: A single-center perspective.

Newborn seizures are frequent in preterm newborns and indicate brain lesions in many cases. The objective of this observational study was to investigate the long-term outcome of very-low-birth-weight (VLBW) and low-birth-weight (LBW) preterm infants with neonatal seizures. We examined 54 preterm infants (40 VLBW and 14 LBW cases) born between 2008 and 2011 with clinical seizures during the neonatal period confirmed by interictal or ictal electroencephalography recordings in a retrospective single-center study. Neurodevelopmental follow-up included an expert neurological examination and cognitive testing (Kaufman Assessment Battery for Children) at a mean age of six years. The (mean±standard deviation) gestational ages of the VLBW and LBW infants were 27.2±1.9 weeks and 33.4±1.7 weeks, respectively, and the postnatal age at seizure onset was 13±11 days in VLBW infants and 9±8 days in LBW infants, with a wide range of one to 62 days. LBW infants more frequently developed non-motor seizures (50.0%) than VLBW infants did (25.0%), and higher-grade intracranial hemorrhage was the predominant etiology in the VLBW group (18.0%), while the etiology in the LBW group was more heterogeneous and included central nervous system malformations and genetic syndromes. At the mean age of 6.2±2.0, years, 25/54 patients were assessed and 44.4% of the VLBW group and 71.4% of the LBW group showed intellectual impairment. Infantile cerebral palsy was present in 22% of VLBW and 42.9% of LBW infants, respectively. The present analysis of long-term neurodevelopmental outcomes of preterm neonates who experienced seizures shows that the risk for intellectual impairment is not limited only to VLBW infants but may significantly affect LBW infants as well. The etiological spectrum differs in relation to gestational age.

Focal non-motor seizures and subsequent focal motor seizures as the main clinical expression of GLUT-1 deficiency.

The seizure type most frequently described in GLUT1 deficiency is generalized (mainly absence). We report the case of a young boy who, as the main clinical manifestation presented with focal non-motor, and then focal motor seizures. At the age of 3months episodes of face pallor/cyanosis and hypotonus lasting about 1min, occurred. They were initially misdiagnosed as gastroesophageal reflux. These episodes disappeared spontaneously at 6months of age. At 12months, episodes similar to the previous ones reappeared. A few months later, a cluster of several episodes manifest as impaired responsiveness and vomiting occurred. The patient initially performed long-term video-EEG monitoring (LTVEM) however, no seizures were captured. During a second hospitalization for LTVEM, a focal to bilateral clonic seizure was recorded. Brain MRI was normal. Next Generation Sequencing (NGS) panel for genes associated with epilepsy showed a de novo mutation of SCL2A1 gene. The CSF showed glucose of 41mg/dL, and the CSF/serum glucose ratio was equal to 0.46. The ketogenic diet was started with optimal efficacy in seizure control. Meal-sensitivity in childhood onset focal seizures may be associated with GLUT-1 deficiency syndrome that can be confirmed by biochemical analysis on blood and CSF following diagnostic genetic study.

The Role of Focal Epilepsy Features in Defining SCN1A Mutation-positive Dravet Syndrome as Generalized and Focal Epilepsy.

Background and PurposeThis study was aimed to describe focal epilepsy features of SCN1A mutation-positive Dravet syndrome patients.MethodsA total of 82 SCN1A mutation-positive patients were reviewed retrospectively (39 boys and 43 girls). Seizure type and electroencephalography (EEG) findings were investigated according to the stage, disease onset, and steady state (after age 2 years). Long-term video EEG data were used to classify the seizure type.ResultsFocal seizures at onset and the steady state were found in 54.9% (45/82) and 90% (63/70) of patients, respectively. Afebrile focal seizures were an initial seizure in about one fourth of the patients (22/82, 26.8%). Of 48 seizures captured during long-term video EEG monitoring of 30 patients, 19 seizures were classified as focal onset (39.6%). Of the 19 focal seizures, 12 were either focal motor or focal non-motor seizures, and seven were focal onset bilateral tonic-clonic seizure. Focal epileptiform discharges were more frequent than generalized epileptiform discharges at seizure onset and during the clinical course on conventional EEG (3.7% vs. 0%, 52.9% vs. 32.9%, respectively).ConclusionsOur study provides a comprehensive description of focal epilepsy features of SCN1A mutation-positive Dravet syndrome patients. Recognizing these features as defining the clinical spectrum of Dravet syndrome may lead to earlier genetic diagnosis and tailored management.

The Individual Ictal Fingerprint: Combining Movement Measures With Ultra Long-Term Subcutaneous EEG in People With Epilepsy.

Background: Epileptic seizures are caused by abnormal brain wave hypersynchronization leading to a range of signs and symptoms. Tools for detecting seizures in everyday life typically focus on cardiac rhythm, electrodermal activity, or movement (EMG, accelerometry); however, these modalities are not very effective for non-motor seizures. Ultra long-term subcutaneous EEG-devices can detect the electrographic changes that do not depend on clinical changes. Nonetheless, this also means that it is not possible to assess whether a seizure is clinical or subclinical based on an EEG signal alone. Therefore, we combine EEG and movement-related modalities in this work. We focus on whether it is possible to define an individual “multimodal ictal fingerprint” which can be exploited in different epilepsy management purposes.Methods: This study used ultra long-term data from an outpatient monitoring trial of persons with temporal lobe epilepsy obtained with a subcutaneous EEG recording system. Subcutaneous EEG, an EMG estimate and chest-mounted accelerometry were extracted from four persons showing more than 10 well-defined electrographic seizures each. Numerous features were computed from all three modalities. Based on these, the Gini impurity measure of a Random Forest classifier was used to select the most discriminative features for the ictal fingerprint. A total of 74 electrographic seizures were analyzed.Results: The optimal individual ictal fingerprints included features extracted from all three tested modalities: an acceleration component; the power of the estimated EMG activity; and the relative power in the delta (0.5–4 Hz), low theta (4–6 Hz), and high theta (6–8 Hz) bands of the subcutaneous EEG. Multimodal ictal fingerprints were established for all persons, clustering seizures within persons, while separating seizures across persons.Conclusion: The existence of multimodal ictal fingerprints illustrates the benefits of combining multiple modalities such as EEG, EMG, and accelerometry in future epilepsy management. Multimodal ictal fingerprints could be used by doctors to get a better understanding of the individual seizure semiology of people with epilepsy. Furthermore, the multimodal ictal fingerprint gives a better understanding of how seizures manifest simultaneously in different modalities. A knowledge that could be used to improve seizure acknowledgment when reviewing EEG without video.

Diagnostic Delay in Epilepsy: the Scope of the Problem.

Diagnostic delay is an increasingly recognized issue in epilepsy. At the same time, there is a clear disparity between public awareness of epilepsy and that of other public health issues. A contributing factor for this seems to be a lack of studies testing interventions designed to improve seizure recognition. In this review, we summarize the main findings from recent studies investigating diagnostic delay in epilepsy, highlighting causes, consequences, and potential interventions in future research that may improve quality of care in this population. Building on prior evidence, diagnostic delay in patients with new-onset focal epilepsy has been identified as an important problem for patients with epilepsy. Such delay in diagnosis can lead to delayed treatment and potentially preventable morbidity and mortality including motor vehicle accidents. Nonmotor seizure semiology appears to be a major contributor for delay; such seizures are largely unrecognized when patients present to emergency departments for care. Improving recognition and diagnosis of recurrent nonmotor seizures in emergency departments represents a significant opportunity for improving time to diagnosis, particularly when patients present following a first lifetime motor seizure and meet diagnostic criteria for epilepsy. Diagnostic delay in epilepsy is a significant public health issue and recent studies have highlighted potential areas for intervention.

Different circuitry dysfunction in drug-naive patients with juvenile myoclonic epilepsy and juvenile absence epilepsy

RationaleJuvenile myoclonic epilepsy (JME) and juvenile absence epilepsy (JAE) are generalized epileptic syndromes presenting in the same age range. To explore whether uneven network dysfunctions may underlie the two different phenotypes, we examined drug-naive patients with JME and JAE at the time of their earliest presentation. MethodsPatients were recruited based on typical JME (n = 23) or JAE (n = 18) presentation and compared with 16 age-matched healthy subjects (HS). We analyzed their awake EEG signals by Partial Directed Coherence and graph indexes. ResultsOut-density and betweenness centrality values were different between groups. With respect to both JAE and HS, JME showed unbalanced out-density and out-strength in alpha and beta bands on central regions and reduced alpha out-strength from fronto-polar to occipital regions, correlating with photosensitivity. With respect to HS, JAE showed enhanced alpha out-density and out-strength on fronto-polar regions. In gamma band, JAE showed reduced Global/Local Efficiency and Clustering Coefficient with respect to HS, while JME showed more scattered values. ConclusionsOur data suggest that regional network changes in alpha and beta bands underlie the different presentation distinguishing JME and JAE resulting in motor vs non-motor seizures characterizing these two syndromes. Conversely, impaired gamma-activity within the network seems to be a non-local marker of defective inhibition.

Identification of Ictal Tachycardia in Focal Motor- and Non-Motor Seizures by Means of a Wearable PPG Sensor.

Photoplethysmography (PPG) as an additional biosignal for a seizure detector has been underutilized so far, which is possibly due to its susceptibility to motion artifacts. We investigated 62 focal seizures from 28 patients with electrocardiography-based evidence of ictal tachycardia (IT). Seizures were divided into subgroups: those without epileptic movements and those with epileptic movements not affecting and affecting the extremities. PPG-based heart rate (HR) derived from a wrist-worn device was calculated for sections with high signal quality, which were identified using spectral entropy. Overall, IT based on PPG was identified in 37 of 62 (60%) seizures (9/19, 7/8, and 21/35 in the three groups, respectively) and could be found prior to the onset of epileptic movements affecting the extremities in 14/21 seizures. In 30/37 seizures, PPG-based IT was in good temporal agreement (<10 s) with ECG-based IT, with an average delay of 5.0 s relative to EEG onset. In summary, we observed that the identification of IT by means of a wearable PPG sensor is possible not only for non-motor seizures but also in motor seizures, which is due to the early manifestation of IT in a relevant subset of focal seizures. However, both spontaneous and epileptic movements can impair PPG-based seizure detection.

Performance of ECG‐based seizure detection algorithms strongly depends on training and test conditions

ObjectiveTo identify non‐EEG‐based signals and algorithms for detection of motor and non‐motor seizures in people lying in bed during video‐EEG (VEEG) monitoring and to test whether these algorithms work in freely moving people during mobile EEG recordings.MethodsData of three groups of adult people with epilepsy (PwE) were analyzed. Group 1 underwent VEEG with additional devices (accelerometry, ECG, electrodermal activity); group 2 underwent VEEG; and group 3 underwent mobile EEG recordings both including one‐lead ECG. All seizure types were analyzed. Feature extraction and machine‐learning techniques were applied to develop seizure detection algorithms. Performance was expressed as sensitivity, precision, F 1 score, and false positives per 24 hours.ResultsThe algorithms were developed in group 1 (35 PwE, 33 seizures) and achieved best results (F 1 score 56%, sensitivity 67%, precision 45%, false positives 0.7/24 hours) when ECG features alone were used, with no improvement by including accelerometry and electrodermal activity. In group 2 (97 PwE, 255 seizures), this ECG‐based algorithm largely achieved the same performance (F 1 score 51%, sensitivity 39%, precision 73%, false positives 0.4/24 hours). In group 3 (30 PwE, 51 seizures), the same ECG‐based algorithm failed to meet up with the performance in groups 1 and 2 (F 1 score 27%, sensitivity 31%, precision 23%, false positives 1.2/24 hours). ECG‐based algorithms were also separately trained on data of groups 2 and 3 and tested on the data of the other groups, yielding maximal F 1 scores between 8% and 26%.SignificanceOur results suggest that algorithms based on ECG features alone can provide clinically meaningful performance for automatic detection of all seizure types. Our study also underscores that the circumstances under which such algorithms were developed, and the selection of the training and test data sets need to be considered and limit the application of such systems to unseen patient groups behaving in different conditions.

Long-term seizure outcomes in patients with anti-Leucine-rich glioma-inactivated 1 encephalitis

BackgroundThis study aimed to investigate the semiology of seizure disorders, including electroencephalographic characteristics, and seizure outcomes in participants with anti-leucine-rich glioma-inactivated 1 (LGI-1) encephalitis. MethodsSeventy participants who presented with seizures during the acute phase of anti-LGI-1 encephalitis at Peking Union Medical College Hospital from May 2013 to July 2020 were reviewed. All participants underwent follow-up for longer than 2 years. ResultsAt the time of presentation, 48 (68.6%) participants had generalized seizures and 57 (81.4%) had focal seizures. The most common focal motor seizures were faciobrachial dystonic seizures (FDS). The main manifestations of focal nonmotor seizures were dyscognitive features, goosebumps, and disorders of sensation. All participants received immunomodulatory therapy. Thirty-five (50%) participants were seizure free after 1 year of follow-up, and 48 (68.6%) participants were seizure free over a follow-up of 2 years. Participants with seizures continued longer than 1 year were older than participants whose seizure duration was shorter than 1 year (P = 0.021). However, after an extended follow-up period, the difference between the incidences of seizures based on age was not significant. The frequency of focal motor seizures was higher in participants who became seizure free within 1 year, compared to participants who had seizures for longer than 1 year (75% vs 54.3%, respectively; P = 0.015). Participants with seizures continued over 2 years tended to have focal nonmotor seizures, and tended to show an elevated incidence of abnormal EEG results. Participants receiving early corticosteroid and longer duration immunosuppressant treatments, tended to have a lower risk of persistent seizures and better seizure outcomes, with no statistical significance. ConclusionsMost participants obtained remission from seizures after immunomodulatory therapy. The seizure manifestation of anti-LGI1 encephalitis is diverse and variable. The type of focal seizures may affect the outcome of participants with seizures. Older age could lead to longer duration of the seizure disorder, but did not affect the rate of seizures over the long term. Early and prolonged administration of immunomodulatory therapy may be useful for shortening the time to becoming seizure free.

The UK experience of stereoelectroencephalography in children: An analysis of factors predicting the identification of a seizure‐onset zone and subsequent seizure freedom

Stereoelectroencephalography (SEEG) is being used more frequently in the pre-surgical evaluation of children with focal epilepsy. It has been shown to be safe in children, but there are no multicenter studies assessing the rates and factors associated with the identification of a putative seizure-onset zone (SOZ) and subsequent seizure freedom following SEEG-guided epilepsy surgery. Multicenter retrospective cohort study of all children undergoing SEEG at six of seven UK Children's Epilepsy Surgery Service centers from 2014 to 2019. Demographics, noninvasive evaluation, SEEG, and operative factors were analyzed to identify variables associated with the identification of a putative SOZ and subsequent seizure freedom following SEEG-guided epilepsy surgery. One hundred thirty-five patients underwent 139 SEEG explorations using a total of 1767 electrodes. A putative SOZ was identified in 117 patients (85.7%); odds of successfully finding an SOZ were 6.4 times greater for non-motor seizures compared to motor seizures (p=0.02) and 3.6 times more if four or moreseizures were recorded during SEEG (p=0.03). Of 100 patients undergoing surgical treatment, 47 (47.0%) had an Engel class I outcome at a median follow-up of 1.3years; the only factor associated with outcome was indication for SEEG (p=0.03); an indication of "recurrence following surgery/treatment" had a 5.9 times lower odds of achieving seizure freedom (p=0.002) compared to the "lesion negative" cohort, whereas other indications ("lesion positive, define extent," "lesion positive, discordant noninvasive investigations" and "multiple lesions") were not statistically significantly different. This large nationally representative cohort illustrates that SEEG-guided surgery can still achieve high rates of seizure freedom. Seizure semiology and the number of seizures recorded during SEEG are important factors in the identification of a putative SOZ, and the indication for SEEG is an important factor in postoperative outcomes.

Parieto-premotor functional connectivity changes during parietal lobe seizures are associated with motor semiology

ObjectivesParietal lobe seizures (PLS) are characterized by multiple clinical manifestations including motor signs. The mechanisms underlying the occurrence of motor signs are poorly understood. The main objective of this work was to estimate the functional coupling of brain regions associated with this clinical presentation. MethodsWe retrospectively selected patients affected by drug-resistant epilepsy who underwent Stereoelectroencephalography (SEEG) for pre-surgical evaluation and in whom the seizure onset zone (SOZ) was located in the parietal cortex. The SOZ was defined visually and quantitatively by the epileptogenicity index (EI) method. Two groups of seizures were defined according to the presence (“motor seizures”) or the absence (“non-motor seizures”) of motor signs. Functional connectivity (FC) estimation was based on pairwise nonlinear regression analysis (h2 coefficient). To study FC changes between parietal, frontal and temporal regions, for each patient, z-score values of 16 cortico-cortical interactions were obtained comparing h2 coefficients of pre-ictal, seizure onset and seizure propagation periods. ResultsWe included 22 patients, 13 with “motor seizures” and 9 with “non-motor seizures”. Resective surgery was performed in 14 patients, 8 patients had a positive surgical outcome (Engel’s class I and II). During seizure onset period, a decrease of FC was observed and was significantly more important (in comparison with background period) in “motor” seizures. This was particularly observed between parietal operculum/post-central gyrus (OP/PoCg) and mesial temporal areas. During seizure propagation, a FC increase was significantly more important (in comparison with seizure onset) in “motor seizures”, in particular between lateral pre-motor (pmL) area and precuneus, pmL and superior parietal lobule (SPL) and between inferior parietal lobule (IPL) and supplementary motor area (SMA). ConclusionsOur study shows that motor semiology in PLS is accompanied by an increase of FC between parietal and premotor cortices, significantly different than what is observed in PLS without motor semiology. SignificanceOur results indicate that preferential routes of coupling between parietal and premotor cortices are responsible for the prominent motor presentation during PLS.

Seizure frequency discrepancy between subjective and objective ictal electroencephalography data in dogs.

BackgroundMany studies of epilepsy in veterinary medicine use subjective data (eg, caregiver‐derived histories) to determine seizure frequency. Conversely, in people, objective data from electroencephalography (EEG) are mainly used to diagnose epilepsy, measure seizure frequency and evaluate efficacy of antiseizure drugs. These EEG data minimize the possibility of the underreporting of seizures, a known phenomenon in human epileptology.ObjectiveTo evaluate the correlation between reported seizure frequency and EEG frequency of ictal paroxysmal discharges (PDs) and to determine whether seizure underreporting phenomenon exists in veterinary epileptology.AnimalsThirty‐three ambulatory video‐EEG recordings in dogs showing ≥1 ictal PD, excluding dogs with status epilepticus.MethodsRetrospective observational study. Ictal PDs were counted manually over the entire recording to obtain the frequency of EEG seizures. Caregiver‐reported seizure frequency from the medical record was categorized into weekly, daily, hourly, and per minute seizure groupings. The Spearman rank test was used for correlation analysis.ResultsThe coefficient value (r s) comparing reported seizure to EEG‐confirmed ictal PD frequencies was 0.39 (95% confidence interval [CI] = 0.048‐0.64, P = .03). Other r s values comparing history against various seizure types were: 0.36 for motor seizures and 0.37 for nonmotor (absence) seizures.Conclusions and Clinical ImportanceA weak correlation was found between the frequency of reported seizures from caregivers (subjective data) and ictal PDs on EEG (objective data). Subjective data may not be reliable enough to determine true seizure frequency given the discrepancy with EEG‐confirmed seizure frequency. Confirmation of the seizure underreporting phenomenon in dogs by prospective study should be carried out.

Migrating Focal Seizures and Myoclonic Status in ARV1-Related Encephalopathy.

ObjectiveTo report longitudinal clinical, EEG, and MRI findings in 2 sisters carrying compound heterozygous ARV1 mutations and exhibiting a peculiar form of developmental and epileptic encephalopathy (DEE). Neuropathologic features are also described in one of the sisters.MethodsClinical course description, video-EEG polygraphic recordings, brain MRI, skin and muscle biopsies, whole-exome sequencing (WES), and brain neuropathology.ResultsSince their first months of life, both girls exhibited severe axial hypotonia, visual inattention, dyskinetic movements, severe developmental delay, and slow background EEG activity. Intractable nonmotor seizures started in both at the eighth month of life, exhibiting the electroclinical characteristics of epilepsy of infancy with migrating focal seizures (EIMFS). In the second year of life, continuous epileptiform EEG activity of extremely high amplitude appeared in association with myoclonic status, leading to severely impaired alertness and responsiveness. Repeated brain MRI revealed progressive atrophic changes and severe hypomyelination. WES identified a compound heterozygous in the ARV1 gene [(p.Ser122Glnfs*7) and (p.Trp163*)] in one patient and was subsequently confirmed in the other. Both sisters died prematurely during respiratory infections. Postmortem neuropathologic examination of the brain, performed in one, revealed atrophic brain changes, mainly involving the cerebellum.ConclusionsThis report confirms that biallelic ARV1 mutations cause a severe form of DEE and adds epilepsy with migrating focal seizures and myoclonic status to the spectrum of epilepsy phenotypes. Considering the potential role of human ARV1 in glycosylphosphatidylinositol (GPI) anchor biosynthesis, this severe syndrome can be assigned to the group of inherited GPI deficiency disorders, with which it shares remarkably similar clinical and neuroimaging features. ARV1 should be considered in the genetic screening of individuals with EIMFS.

Non-invasive wearable seizure detection using long–short-term memory networks with transfer learning

Objective. The detection of seizures using wearable devices would improve epilepsy management, but reliable detection of seizures in an ambulatory environment remains challenging, and current studies lack concurrent validation of seizures using electroencephalography (EEG) data. Approach. An adaptively trained long–short-term memory deep neural network was developed and trained using a modest number of seizure data sets from wrist-worn devices. Transfer learning was used to adapt a classifier that was initially trained on intracranial electroencephalography (iEEG) signals to facilitate classification of non-EEG physiological datasets comprising accelerometry, blood volume pulse, skin electrodermal activity, heart rate, and temperature signals. The algorithm’s performance was assessed with and without pre-training on iEEG signals and transfer learning. To assess the performance of the seizure detection classifier using long-term ambulatory data, wearable devices were used for multiple months with an implanted neurostimulator capable of recording iEEG signals, which provided independent electrographic seizure detections that were reviewed by a board-certified epileptologist. Main results. For 19 motor seizures from 10 in-hospital patients, the algorithm yielded a mean area under curve (AUC), a sensitivity, and an false alarm rate per day (FAR/day) of 0.98, 0.93, and 2.3, respectively. Additionally, for eight seizures with probable motor semiology from two ambulatory patients, the classifier achieved a mean AUC of 0.97 and an FAR of 2.45 events/day at a sensitivity of 0.9. For all seizure types in the ambulatory setting, the classifier had a mean AUC of 0.82 with a sensitivity of 0.47 and an FAR of 7.2 events/day. Significance. The performance of the algorithm was evaluated using motor and non-motor seizures during in-hospital and ambulatory use. The classifier was able to detect multiple types of motor and non-motor seizures, but performed significantly better on motor seizures.

Seizure phenotype in CLN3 disease and its relation to other neurologic outcome measures.

CLN3 disease is a pediatric neurodegenerative condition wherein seizures are common. The most common disease-causing variant is an ~1-kb deletion in CLN3. We investigated seizure phenotype in relation to genotype and to adaptive behavior, MR spectroscopy and CSF biochemical markers in a CLN3 cohort. We performed seizure phenotyping using clinical history, EEG, and the Unified Batten Disease Rating Scale (UBDRS) seizure score. We assessed correlations of seizure severity with disease severity (UBDRS capability), adaptive behavior composite score (ABC; Vineland-3), glutamate+glutamine+GABA and N-acetylaspartate+N-acetylaspartyl glutamate (MR spectroscopy), and CSF neurofilament light chain (NEFL) levels. In 20 participants, median age was 10.7 years (IQR=7.8). Eighteen completed baseline EEG; 12 had a 1-year follow-up. Seizures were reported in 14 (8 1-kb deletion homozygotes), with median age at onset of 10.0 (IQR=6.8). Epileptiform discharges were noted in 15 (9 homozygotes). Bilateral tonic clonic (n=11) and nonmotor seizures (n=7) were most common. UBDRS seizure score correlated with age (rp=0.50; [0.08,0.77]; P=.02), UBDRS capability (rp=-0.57; [-0.81,-0.17]; P=.009) and ABC (rp=-0.66; [-0.85,-0.31]; P=.001) scores, glutamate+glutamine+GABA (rp=-0.54; [-0.80,-0.11]; P=.02) and N-acetylaspartate+N-acetylaspartyl glutamate (rp=-0.54; [-0.80,-0.11]; P=.02), and CSF NEFL (rp=0.65; [0.29,0.85]; P=.002) levels. After controlling for age, correlations with ABC and CSF NEFL remained significant. In our CLN3 cohort, seizures and epileptiform discharges were frequent and often started by age 10 years without significant difference between genotypes. ABC and CSF NEFL correlate with UBDRS seizure score, reflecting the role of seizures in the neurodegenerative process. Longitudinal evaluations in a larger cohort are needed to confirm these findings.

Different faces of frontal lobe epilepsy: The clinical, electrophysiologic, and imaging experience of a tertiary center

ObjectiveFrontal lobe epilepsy (FLE) is the second most common epilepsy among drug-resistant focal epilepsies. Semiologic and electrophysiologic features of FLE present some difficulties because frontal lobe seizures are brief, accompanied by complex motor activities and emotional signs. The rich connectivity of the frontal lobe with other areas leads to the rapid and widespread propagation of seizure activity, which contribute to the difficulty of evaluating the semiologic and EEG patterns of the seizure. In this study, we investigated semiologic, interictal, ictal, and postictal EEG characteristics; the imaging data of patients with FLE and the possible contribution of these data to localization and lateralization of seizures. Materials and methodsThe medical records of patients who were diagnosed as having FLE between 2010 and 2019 in our clinic were evaluated retrospectively. The diagnosis of FLE was considered either when patients had a structural lesion in the frontal region or seizure semiology and EEG characteristics were compatible with FLE. Clinical, electrophysiologic, and imaging features were investigated in these patients. ResultsWe have evaluated 146 seizures in 36 patients (17 lesional and 19 non-lesional according to MRI). There were 110 focal motor or nonmotor seizures, 18 bilateral tonic-clonic seizures, and 18 subclinical seizures. There were 16 patients with aura. The most common semiologic feature was hyperkinetic movements. Among the interictal EEGs, 30.5 % included focal anomalies. Among the ictal EEGs, 69.1 % were non-localizing or lateralizing. The most common ictal pattern was rhythmic theta activity (21.2 %). In four patients, who had non-localizing or lateralizing EEG, the postictal EEG was informative. Our study showed a low percentage of localized FDG-PET, which, however, involved visual analysis. ConclusionOur results support the previously known difficulties in the determination of the epileptogenic zone of FLE. Semiologic and electrophysiologic correlation studies, longer postictal records, and quantitative analysis of FDG-PET may contribute to a better characterization of the disease.

Epilepsy in the Hippocratic collection: Seizures and syndromes

Despite extensive scholarship, several questions on the view of seizures and epilepsy in the Hippocratic collection have not been answered. The book ‘On the Sacred Disease’ contains descriptions of focal and generalized tonic-clonic seizures, understands the stigma attached to epilepsy, its association with depression, and probably describes auras. Remarkably, the collection presents a physiologic theory of ‘mental’ disease. Other parts of the collection suggest recognition of syndromes such as childhood febrile seizures. Non-motor seizures are not clearly described. There may be a distinction between ‘acute symptomatic’ and recurrent seizures or ‘epilepsy.’ Analysis of the relative occurrence of terms related to ‘epilepsy’ or ‘spasms’ in an online text collection shows a significant difference: ‘epilepsy’ terms are more frequent when seizures are described alone, while ‘spasm’ terms are more frequent in the context of systemic diseases or injuries. This dichotomy suggests, in contrast to previous accounts, possible understanding of the distinction between ‘idiopathic’ and ‘symptomatic’ seizure disorders.

Surgery in intractable epilepsy-physicians' recommendations and patients' decisions.

To identify demographic and clinical variables independently associated with patients' decisions against their physicians' recommendations for resective epilepsy surgery or further scalp video-EEG monitoring (sca-VEM), semi-invasive (sem-)VEM with foramen ovale and/or peg electrodes, and invasive (in-)VEM. Consecutive patients, who underwent presurgical assessment with at least one sca-VEM between 2010 and 2014, were included into this retrospective analysis. Multivariate analysis was used to identify independent variables associated with patients' decisions. Within the study period, 352 patients underwent 544 VEM sessions comprising 451 sca-, 36 sem-, and 57 in-VEMs. Eventually, 96 patients were recommended resective surgery, and 106 were ineligible candidates; 149 patients denied further necessary VEMs; thus, no decision could be made. After sca- or additional sem-VEM, nine out of 51 eligible patients (17.6%) rejected resection. One hundred and ten patients were recommended in-VEM, 52 of those (47.2%) declined. Variables independently associated with rejection of in-VEM comprised intellectual disability (OR 4.721, 95% CI 1.047-21.284), extratemporal focal aware non-motor seizures ("aura") vs. no "aura" (OR 0.338, 95% CI 0.124-0.923), and unilateral or bilateral vs. no MRI lesion (OR 0.248, 95% CI 0.100-0.614 and 0.149, 95% CI 0.027-0.829, respectively). During and after presurgical evaluation, patients with intractable focal epilepsy declined resections and intracranial EEGs, as recommended by their epileptologists, in almost 20% and 50% of cases. This calls for early and thorough counseling of patients on risks and benefits of epilepsy surgery. Future prospective studies should ask patients in depth for specific reasons why they decline their physicians' recommendations.

The Impact of Clinical Seizure Characteristics on Recognition and Treatment of New-onset Focal Epilepsy in Emergency Departments.

Many people with new-onset focal epilepsy initially seek evaluation in emergency departments (EDs), and treatment decisions in EDs can influence likelihood of seizure recurrence. Using data collected for the Human Epilepsy Project (HEP), we assessed the effect of clinical seizure characteristics on ED clinical management. There were 447 participants with new-onset focal epilepsy seen within 4months of treatment initiation who were eligible and enrolled in HEP. Seizure calendars and medical records were collected. Based on clinical descriptions, seizures were categorized by semiology according to International League Against Epilepsy (ILAE) classifications as either focal nonmotor or focal motor seizures. Overall, 279 of 447(62%) of participants had presented to an ED prior to or at time of epilepsy diagnosis. A total of 132 of 246 (53%) with initial nonmotor seizures presented to an ED. Of these, eight (6%) presented with a first-lifetime nonmotor seizure. The other 124 (94%) presented after multiple seizures: seven (5%) with multiple nonmotor seizures and 117 (89%) with a first-lifetime motor seizure after having prior nonmotor seizures. A total of 147 of 201 (73%) participants with initial motor seizures presented to an ED. Of these, 134 (92%) presented with a first-lifetime motor seizure and 13 (9%) with multiple motor seizures. There was no difference in the likelihood of antiseizure medication initiation between participants who had multiple prior nonmotor seizures followed by a motor seizure (thereby fulfilling the criterion for an epilepsy diagnosis) versus those presenting with a single lifetime motor seizure (39% vs. 43%). There was no difference in recognition of seizures as the presenting complaint (85% vs. 87%) or whether the participant was admitted or referred to a neurologist (87% vs. 79%). This study contributes to evidence of underrecognition of nonmotor focal seizure semiologies in ED settings, which can support large-scale interventions aimed at improving recognition, specialist consultation, and treatment in ED settings.