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We report a case of a 27-year-old right-handed gentleman with mutism and seizures diagnosed with Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis without evidence of underlying malignancy. Brain MRI was unremarkable. Clinical seizures were controlled but long-term video-EEG monitoring was needed for better characterization of his clinical manifestations especially that language partially improved. It was crucial to identify whether this mutism was ictal in origin or not. Ictal brain Positron Emission Tomography with 18 F-fluorodeoxyglucose (FDGPET) scan combined with EEG was done. It revealed left fronto-temporal, parietal, and crossed cerebellar hypermetabolism (or diaschisis) concomitant to the underlying rhythmic focal delta activity on EEG. Beside anti-epileptic drugs he was treated with escalating immunotherapy (intravenous solumedrol then immunoglobulins then full rituximab course). Six months later, EEG combined to FDG-PET scan were repeated, and were normal. At 3 years follow up the patient remains neurologically stable and seizure-free, off anti-epileptics drugs. Performing the FDGPET scan combined to EEG was useful to identify non-convulsive status epilepticus and should be performed early in anti-NMDAR encephalitis to guide treatment.

Background Transcranial direct current stimulation (tDCS) provides a noninvasive polarity-specific constant current to treat epilepsy, through a mechanism possibly involving excitability modulation and neural oscillation. Objective To determine whether EEG oscillations underlie the interictal spike changes after tDCS in rats with chronic spontaneous seizures. Methods Rats with kainic acid-induced spontaneous seizures were subjected to cathodal tDCS or sham stimulation for 5 consecutive days. Video-EEG recordings were collected immediately pre- and post-stimulation and for the subsequent 2 weeks following stimulation. The acute pre-post stimulation and subacute follow-up changes of interictal spikes and EEG oscillations in tDCS-treated rats were compared with sham. Ictal EEG with seizure behaviors, hippocampal brain-derived neurotrophic factor (BDNF) protein expression, and mossy fiber sprouting were compared between tDCS and sham rats. Results Interictal spike counts were reduced immediately following tDCS with augmented delta and diminished beta and gamma oscillations compared with sham. Cathodal tDCS also enhanced delta oscillations in normal rats. However, increased numbers of interictal spikes with a decrease of delta and theta oscillations were observed in tDCS-treated rats compared with sham during the following 2 weeks after stimulation. Resuming tDCS suppressed the increase of interictal spike activity. In tDCS rats, hippocampal BDNF protein expression was decreased while mossy fiber sprouting did not change compared with sham. Conclusions The inverse relationship between the changes of delta oscillation and interictal spikes during tDCS on and off stimulation periods indicates that an enhanced endogenous delta oscillation underlies the tDCS inhibitory effect on epileptic excitability.

الملخص: أهداف البحث: صممت الدراسة لتقييم النتاج والنمط والعوامل التي ترتبط بشكل مستقل بتشوهات التخطيط الدماغي في صرع الطفولة لدى السعوديين. طرق البحث: وصفنا السمات الأولى لمخطط كهربية الدماغ وقيمنا العوامل المرتبطة بها في عينة من الأطفال المصابين بالصرع في المجتمع السعودي. اعتمد الاتحاد الدولي لجمعيات تخطيط كهربية الدماغ والفيزيولوجيا العصبية السريرية تعريف التصريفات الصرعية بين النشبات (نشاط الصرع بين النشبات) في الدراسة. النتائج: كان ٧٥٦ مريضا من الأطفال منهم ٤٢٧ (٥٦.٥٪) من الذكور و٣٢٩ (٤٣.٥٪) من الإناث مع التشخيص السريري للصرع لديهم تخطيط كهربية الدماغ. سريريا، النوبة كانت معممة في ٦١٩ (٨١.٩٪) مريضا وبؤرية في ١٣٧ (١٨.١٪) مريضا. عانى ٣٩٧ مريضا (٥٢.٥١٪) من شذوذ في مخطط كهربية الدماغ، بينما كان مخطط كهربية الدماغ طبيعيا عند ٣٥٩ مريضا (٤٧.٤٩٪). كان تواتر النوبة والجنس ووجود تاريخ عائلي للصرع والعمر منبئات مستقلة لوجود تشوهات تخطيط كهربية الدماغ. الاستنتاجات: كشفت الدراسة أن نتاج ٥٢٪ من مخطط كهربية الدماغ غير طبيعي لدى الأطفال المصابين بالصرع. وكان العمر والجنس والتاريخ العائلي وتواتر النوبات منبئات مستقلة لوجود شذوذ في مخطط كهربية الدماغ في صرع الطفولة. Abstract: Objective: The study was designed to evaluate the yield, pattern, and factors that are independently associated with electroencephalography (EEG) abnormalities in childhood epilepsy in a Saudi population. Methods: We characterised the features of the first EEG and evaluated the associated factors in children with epilepsy in a Saudi population. The features of interictal epileptiform discharges (interictal epileptiform activity (IEA)) adopted by the International Federation of Societies for Electroencephalography and Clinical Neurophysiology were used in the study. Result: A total of 756 paediatric patients, comprised of 427 men (56.5%) and 329 women (43.5%) with a clinical diagnosis of epilepsy, underwent EEG. Clinically, seizure was generalised in 619 (81.9%) patients and focal in 137 (18.1%). Among the patients, 397 (52.51%) had an abnormal EEG, while EEG was normal in 359 (47.49%) patients. Seizure frequency, gender, family history of epilepsy, and age were independent predictors of the presence of EEG abnormalities. Conclusion: This study revealed a yield of 52% abnormal EEG findings in children with epilepsy. Age, gender, family history, and seizure frequency were independent predictors of the presence of EEG abnormalities in childhood epilepsy.

Highlights • We show that typical absence seizures (AS) and hyperventilation-induced high amplitude rhythmic slowing (HIHARS) or HIHARS with Altered Awareness (HIHARSAA) can coexist in the same patient, but never at the same time. • We found that alkalosis and dysfunction of the same neural network are involved in both AS and HIHARS. • AS and HIHARS should be better recognized to avoid misdiagnosis and overtreatment. • AS and HIHARS can coexist in the same patient, but never at the same time., Background Typical absence seizures (AS) are epileptic phenomena typically appearing in children 4–15 years of age and can be elicited by hyperventilation (HV). Hyperventilation-induced high-amplitude rhythmic slowing (HIHARS) represents a paraphysiological response during HV and may manifest with alteration of awareness (HIHARSAA). To date, HIHARSAA has mostly been described in patients without epilepsy. Aim To describe five patients with treatment-responsive typical AS who, after becoming seizure free, presented with HIHARSAA. Methods By using video-electroencephalographic recording (Video-EEG), we describe differential clinical characteristics and ictal electrophysiological patterns of both typical AS and HIHARSAA. Results We demonstrate that when HIHARSAA occurs in patients with typical AS there is a temporal window between the two phenomena. This suggests that the presence of typical AS precludes the appearance of HIHARSAA. Conclusions We hypothesize that alkalosis and dysfunction of the same neural network are involved in both typical AS and HIHARSAA and that their distinct electroclinic manifestations are due to the involvement of different ion channels. Significance A better understanding of the characteristics of typical AS and HIHARSAA and of the role of alkalosis in both, can help avoiding misdiagnosis and identifying more suitable therapies for typical AS.

Highlights • Methohexital-induced LPDs occur rarely during Wada testing in epilepsy. • Ipsilateral LPDs may impair memory testing during the Wada. • EEG monitoring during the Wada test is recommended., Objective The Wada test is used to evaluate language lateralization and memory performance after inactivation of an isolated cerebral hemisphere. Methohexital a short-acting barbiturate has a history of use to induce interictal discharges during intraoperative corticography. We report a new finding of activation of lateralized periodic discharges (LPDs) after Methohexital injection. Methods We retrospectively reviewed 174 consecutive adult patients who underwent Wada testing in preparation for epilepsy surgery (N = 129, 74%) or brain tumor resection (N = 45, 26%) at the University of Michigan to determine the frequency of induced periodic discharges by methohexital. Results Four epilepsy patients (2.29%) had methohexital-induced LPDs within a median of 2 s (1–99 s) of the injection and lasting a median of 4 min (3–10 min) after a total of 7 injections. All LPDs occurred ipsilateral to the injection hemisphere in the known region of interictal epileptiform discharges. LPDs were not induced in brain tumor patients. In one patient, LPDs occurred during memory testing, and this patient's memory performance was below expectation based on pre-test neuropsychological testing. Conclusions Methohexital can induce LPDs in ipsilateral hemisphere and that can potentially affect memory performance. Significance This observation indicates that concurrent EEG monitoring during the Wada test is important and that induced discharges should be considered when interpreting Wada test results.

Objective To provide guidance for ECT practitioners in utilising the ictal EEG to inform treatment decisions. Methods A systematic review of studies examining the ictal EEG, treatment technique, seizure threshold and treatment outcomes was conducted. MEDLINE, EMBASE and PsycINFO databases were searched up to July 31, 2019. Studies were included if they examined the use of ECT in human subjects and compared an ictal EEG analysis (either quantitative or manually rated) with either: a) clinical outcomes, b) seizure threshold/threshold change, c) ECT dosing decisions, or d) different aspects of ECT technique (comparison of different electrode placements, pulse widths, waveforms, or dose/dose relative to seizure threshold). Results A total of 853 studies were identified, with 44 meeting inclusion criteria. A qualitative review revealed ictal EEG indices have been linked to therapeutic outcome, though the strength of this relationship appears modest. Ictal EEG features are influenced by variations in ECT treatment technique. Serial ictal EEG monitoring can detect changes in seizure threshold across an ECT course for right unilateral brief and ultrabrief pulse ECT. Conclusion While there is some relationship between ictal EEG manifestation and treatment outcomes, the primary utility of ictal EEG monitoring during an ECT course may lie in the capacity to detect changes in seizure threshold and adjust dosing accordingly. Prospective validation of a dosing regime informed by serial ictal EEG monitoring is warranted.

Objective Using interictal epileptiform discharges (IEDs), consisting of spikes and post-spike slow waves (PSSs), and IED-related high-frequency activities (HFAs), we elucidated inhibitory effects of electrical cortical stimulation (ECS) on human epileptic foci. Methods We recruited 8 patients with intractable focal epilepsy, and 50-Hz ECS was applied to the seizure-onset zone (SOZ) and non-SOZ. Before (5-min) and after (20-min) ECS, we evaluated the number of IED, the amplitudes of spikes and PSSs, spike-related HFA power, and PSS-related low gamma (30–50 Hz) activities. Results SOZ stimulation significantly decreased the number of IEDs and amplitude of spikes. Spike-related HFA power values in fast ripple (200–300 Hz) and ripple (80–150 Hz) bands were significantly suppressed only by SOZ stimulation in 4 and 3 patients, respectively. Among 4 patients with discrete PSSs, the amplitude ratio of spike/PSS decreased and the PSS-related low gamma activity power increased significantly in 2 patients and marginally in 1 patient. Conclusions ECS potentially modulates cortical excitability by reducing excitation and increasing inhibition, and monitoring IED-related HFAs may help achieve the optimal effects of ECS. Significance IED and IED-related HFAs are dynamic, potential surrogate markers for epileptic excitability during the interictal period.

Summary: To understand the conditions necessary to initiate and terminate seizures, we investigate optogenetically induced hippocampal seizures with LFP, fMRI, and optogenetic inhibition. During afterdischarge induction using optogenetics, LFP recordings show that stimulations with earlier ictal onset times are more likely to result in afterdischarges and are more difficult to curtail with optogenetic inhibition. These results are generalizable across two initiation sites, the dorsal and ventral hippocampus. fMRI shows that afterdischarges initiated from the dorsal or ventral hippocampus exhibit distinct networks. Short-duration seizures initiated in the dorsal and ventral hippocampus are unilateral and bilateral, respectively, while longer-duration afterdischarges recruit broader, bilateral networks. When optogenetic inhibition is ineffective at stopping seizures, the network activity spreads more extensively but largely overlaps with the network activity associated with seizures that could be curtailed. These results provide insights into how seizures can be inhibited, which has implications for targeted seizure interventions. : Duffy et al. show that success in generating or curtailing seizures is related to their onset time, with inhibition proving less effective on earlier-onset afterdischarges. To identify downstream targets for intervention, fMRI is used to map the seizure network of afterdischarges initiated from the dorsal and ventral hippocampus. Keywords: seizure, epilepsy, hippocampus, fMRI, optogenetrics, generation, inhibition, stopping, network, afterdischarge

Highlights • MEG may aid in the localization of the epileptogenic zone in the parietal lobe. • SAMepi – a novel kurtosis beamformer – results in localizations similar to those of the ECD analysis. • A unifocal result in both the ECD and the SAMepi analysis is associated with a good clinical outcome., Objective To evaluate a novel analysis method (SAMepi) in the localization of interictal epileptiform magnetoencephalographic (MEG) activity in parietal lobe epilepsy (PLE) patients in comparison with equivalent current dipole (ECD) analysis. Methods We analyzed the preoperative interictal MEG of 17 operated PLE patients utilizing visual analysis and: (1) ECD with a spherical conductor model; (2) ECD with a boundary element method (BEM) conductor model; and (3) SAMepi – a kurtosis beamformer method. Localization results were compared between the three methods, to the location of the resection and to the clinical outcome. Results Fourteen patients had an epileptiform finding in the visual analysis; SAMepi detected spikes in 11 of them. A unifocal finding in both the ECD and in the SAMepi analysis was associated with a better chance of seizure-freedom (p = 0.02). There was no significant difference in the distances from the unifocal MEG localizations to the nearest border of the resection between the different analysis methods. Conclusions Localizations of unifocal interictal spikes detected by SAMepi did not significantly differ from the conventional ECD localizations. Significance SAMepi – a novel semiautomatic analysis method – is useful in localizing interictal epileptiform MEG activity in the presurgical evaluation of parietal lobe epilepsy patients.

Background: The relationship between migraine and depression has been thoroughly investigated, indicating a bidirectional comorbidity. The exact temporal relationship between acute depressive symptoms (mood changes) and the various phases of the migraine attack has not yet been examined. Methods: We performed a prospective diary study in n = 487 participants with migraine. Participants filled out a daily diary on migraine and acute depressive symptoms during a 1-month period. We randomly selected one migraine attack per participant, consisting of six days around an attack, including the interictal, premonitory, ictal, and postdromal phases. Acute depressive symptoms covered five major items from the DSM-5 classification. Primary analysis was performed using a mixed model with post-hoc testing. We also tested whether lifetime depression influenced the presence of acute depressive symptoms. Results: During a migraine headache day, patients scored higher on acute depressive symptoms than on all other days of the migraine attack (p < 0.001). There were no early warning signs for an upcoming headache attack through acute depressive symptomatology. Migraine patients with lifetime depression scored overall higher during the migraine attack than those without lifetime depression (p < 0.001). Limitations: Migraine attacks were based on self-reported migraine and one migraine attack per patient was randomly selected.Conclusion: We now clearly demonstrate that during the migraine headache phase, but not in the prodromal phase, patients report increased depressive symptomatology. No evidence was found for mood changes as an early warning sign for an upcoming migraine attack.

Highlights • Prolonged post-ictal Atrial fibrillation is a rare phenomenon. • Fluttering in the chest after seizures may be post-ictal cardiac arrhythmias. • Post-ictal Atrial fibrillation is captured on Video EEG in our case., It is well known that several types of cardiac arrhythmias can occur after a seizure, with ictal sinus tachycardia being the most common. However, post-ictal atrial fibrillation (PIAF) is a rare phenomenon with significant clinical implications. We describe the case of an epilepsy patient with prolonged PIAF. Our case is that of a 62-year-old female with seizure onset at 51 years of age. She had a left hemispheric meningioma that was resected with ongoing seizures. She described frequent episodes of chest fluttering lasting for several hours post-ictally. During video-EEG monitoring (VEEG), she had a typical seizure with staring and word finding difficulty. This was associated with the occurrence of atrial fibrillation with rapid ventricular rate that lasted 18 hours. We discuss the relation between seizures and prolonged PIAF as it relates to the need for anticoagulation, use of appropriate antiseizure medications, and the possible association with SUDEP.

Summary STXBP1 mutations are associated with encephalopathy, developmental delay, intellectual disability, and epilepsy. While neural networks are known to operate at a critical state in the healthy brain, network behavior during pathological epileptic states remains unclear. Examining activity during periods between well-characterized ictal-like events (i.e., interictal period) could provide a valuable step toward understanding epileptic networks. To study these networks in the context of STXBP1 mutations, we combine a larval zebrafish model with in vivo fast confocal calcium imaging and extracellular local field potential recordings. Stxbp1b mutants display transient periods of elevated activity among local clusters of interacting neurons. These network “cascade” events were significantly larger in size and duration in mutants. At mesoscale resolution, cascades exhibit neurodevelopmental abnormalities. At single-cell scale, we describe spontaneous hyper-synchronized neuronal ensembles. That calcium imaging reveals uniquely disordered brain states during periods between pathological ictal-like seizure events is striking and represents a potential interictal biomarker., Graphical abstract, Highlights • Calcium imaging in genetic epilepsy zebrafish model to study the interictal state • Network cascade activity was more prominent in stxbp1b mutant zebrafish • stxbp1b mutants characterized by spontaneous hyper-synchronized neuronal ensembles, Optical imaging; Molecular neuroscience; Cellular neuroscience

Background Variation in the temporal patterns of electrical pulses in stimulation trains has opened a new field of opportunity for the treatment of neurological disorders, such as pharmacoresistant temporal lobe epilepsy. Whether this novel type of stimulation affects epileptogenesis remains to be investigated. Objective The purpose of this study was to analyze the effects of temporally irregular deep brain stimulation on kindling-induced epileptogenesis in rats. Methods Temporally irregular deep brain stimulation was delivered at different times with respect to the kindling stimulation. Behavioral and electrographic changes on kindling acquisition were compared with a control group and a temporally regular deep brain stimulation-treated group. The propagation of epileptiform activity was analyzed with wavelet cross-correlation analysis, and interictal epileptiform discharge ratios were obtained. Results Temporally irregular deep brain stimulation delivered in the epileptogenic focus during the interictal period shortened the daily afterdischarge duration, slowed the progression of seizure stages, diminished the generalized seizure duration and interfered with the propagation of epileptiform activity from the seizure onset zone to the ipsi- and contralateral motor cortex. We also found a negative correlation between seizure severity and interictal epileptiform discharges in rats stimulated with temporally irregular deep brain stimulation. Conclusion These results provide evidence that temporally irregular deep brain stimulation interferes with the establishment of epilepsy by delaying epileptogenesis by almost twice as long in kindling animals. Thus, temporally irregular deep brain stimulation could be a preventive approach against epilepsy.

Despite decades of research, our understanding of epilepsy, including how seizures are generated and propagate, is incomplete. However, there is growing recognition that epilepsy is more than just the occurrence of seizures, with patients often experiencing comorbid deficits in cognition that are poorly understood. In addition, the available therapies for treatment of epilepsy, from pharmaceutical treatment to surgical resection and seizure prevention devices, often exacerbate deficits in cognitive function. In this review, we discuss the hypothesis that seizure generation and cognitive deficits have a similar pathological source characterized by, but not limited to, deficits in theta oscillations and their influence on interneurons. We present a new framework that describes oscillatory states in epilepsy as alternating between hyper- and hypo-synchrony rather than solely the spontaneous transition to hyper-excitability characterized by the seizures. This framework suggests that as neural oscillations, specifically in the theta range, vary their tempo from a slowed almost adagio tempo during interictal periods to faster, more rhythmic allegretto tempo preictally, they impact the function of interneurons, modulating their ability to control seizures and their role in cognitive processing. This slow wave oscillatory framework may help explain why current therapies that work to reduce hyper-excitability do not completely eliminate seizures and often lead to exacerbated cognitive deficits.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality, but the relative importance of underlying cardiac and respiratory mechanisms remains unclear. To illuminate the interactions between seizures, respiration, cardiac function, and sleep that contribute to SUDEP risk, here we developed a mouse epilepsy monitoring unit (EMU) to simultaneously record video, electroencephalography (EEG), electromyography (EMG), plethysmography, and electrocardiography (ECG) in a commonly used genetic model of SUDEP, the Kcna1 knockout (Kcna1(–/–)) mouse. During interictal periods, Kcna1(–/–) mice exhibited an abnormal absence of post-sigh apneas and a 3-fold increase in respiratory variability. During spontaneous convulsive seizures, Kcna1(–/–) mice displayed an array of aberrant breathing patterns that always preceded cardiac abnormalities. These findings support respiratory dysfunction as a primary risk factor for susceptibility to deleterious cardiorespiratory sequelae in epilepsy and reveal a new role for Kcna1-encoded Kv1.1 channels in the regulation of basal respiratory physiology.

High-pass filtering (> 80 Hz) of EEG signals has enabled neuroscientists to analyze high-frequency oscillations (HFOs; i.e., ripples: 80–200 Hz and fast ripples: 250–500 Hz) in epileptic patients presenting with focal seizures and in animal models mimicking this condition. Evidence obtained from these studies indicate that HFOs mirror pathological network activity that may initiate and sustain ictogenesis and epileptogenesis. HFOs are observed in temporal lobe regions of epileptic animals during interictal periods but they also occur before seizure onset and during the ictal period, suggesting that they can pinpoint to the mechanisms of seizure generation. Accordingly, ripples and fast ripples predominate during two specific seizure onset patterns termed low-voltage fast and hypersynchronous, respectively. In this review we will: (i) summarize these experimental studies; (ii) consider the evolution of HFOs over time during epileptogenesis; (iii) address data obtained with optogenetic stimulating procedures both in vitro and in vivo, and (iv) take into account the impact of anti-epileptic drugs on HFOs. We expect these findings to contribute to understanding the neuronal mechanisms leading to ictogenesis and epileptogenesis thus leading to the development of mechanistically targeted anti-epileptic strategies.

Traumatic brain injury (TBI) accounts for approximately 16% of acute symptomatic seizures which usually occur in the first week after trauma. Children are at higher risk for post-traumatic seizures than adults. Post-traumatic seizures are a risk factor for delayed development of epilepsy. Delayed, chronic post-traumatic epilepsy is preceded by a silent period during which therapeutic interventions may arrest, revert or prevent epileptogenesis. A number of recent review articles summarize the most important features of post-traumatic seizures and epilepsy; this review will instead focus on the link between cerebrovascular permeability, epileptogenesis and ictal events after TBI. The possibility of acting on the blood-brain barrier (BBB) and the neurovascular unit to prevent, disrupt or treat post-traumatic epilepsy is also discussed. Finally, we describe the latest quest for biomarkers of epileptogenesis which may allow for a more targeted intervention.

Highlights • Symptomatic generalised epilepsy rarely may manifest with subtle seizure semiology. • Detailed polygraphic EEG with video differentiates the ictal-interictal continuum. • Identification of subtle seizures enables true seizure burden to be identified., Introduction Perioral myoclonus (POM) is a rare seizure manifestation which may present in either idiopathic or structural epilepsies. There has been little description of the rarer ictal manifestations in POM in generalised epilepsy. It is important during Electroencephalography (EEG) testing to carefully monitor clinical change during inter-ictal bursts, as this condition, demonstrated in this case, can exhibit extremely subtle seizure semiology which can allude typical clinical examination. Case Presented is a four-year-old boy with a complex medical history, referred following episodes up to six times per day consisting of perioral myoclonus at a rate of ∼3p/s alongside behavioural arrest lasting up to thirty seconds. Electroencephalography (EEG) recording captured nine seizures within a twenty-five-minute period, where only one seizure was of his stereotyped semiology. Additional seizures commonly adopted a novel semiology of isolated nostril (“flaring”) myoclonus, on some occasions with concomitant head bobbing. Surface EMG and high resolution zoomed video revealed time-locked myoclonus to the generalised spike and wave discharges seen in on EEG. Significance The findings demonstrate a novel epileptic seizure manifestation of nostril myoclonus, in which detailed electroencephalographic and video correlation was essential to minimise risk of underestimating seizure frequency in this rare and complex epilepsy disorder.

We describe a 23-year-old woman with previous right temporal lobe surgeries for underlying cortical dysplasia, presenting with drug-resistant right hemispheric seizures and epilepsia partialis continua (EPC). After anti-seizure medication adjustments, she developed focal status epilepticus with progressive EEG and neuroimaging changes. Cerebrospinal fluid and serum autoimmune panels were negative except for an elevated serum acetylcholine-receptor antibody titer, but she underwent immunosuppressive therapy. Stereotactic-EEG evaluation demonstrated multifocal independent ictal patterns in the right hemisphere. Rasmussen's Syndrome was confirmed by brain biopsy, and a hemispherectomy was performed. This patient demonstrates the rare association of adult-onset EPC with cortical dysplasia, precipitously evolving into Rasmussen's Syndrome., Highlights • Rasmussen's Syndrome (RS) can be associated with focal cortical dysplasia. • Autoimmunity underlies evolution of new-onset EPC in the setting of chronic focal epilepsy, and support a diagnosis of RS. • Hemispherectomy can be an effective intervention in adult-onset RS.

Background Intraoperative electrocorticography (iECoG) recording is recommended for treating cavernoma related epilepsy. However, “interictal” paroxysmal activities are generally recordable but are not always identical to the epileptogenic zone. Case description We surgically treated a 15-year-old girl with drug-resistant epilepsy associated with radiation-induced cavernoma in the right lateral temporal lobe. iECoG revealed paroxysmal activities in the cortex around the cavernoma. Additionally, continuous subclinical “ictal” discharges with high-frequency oscillations (HFO), confined to the histologically non-sclerotic hippocampus, were recorded. Following additional hippocampectomy, a good seizure outcome was obtained. Conclusion iECoG and HFO analysis revealed high epileptogenicity in the non-sclerotic hippocampus of this patient., Highlights • Continuous ictal discharges with high frequency oscillations were recorded in the non-sclerotic hippocampus in a patient with radiation induced cavernoma in the lateral temporal lobe.

Perfusion patterns observed in Subtraction Ictal SPECT Co-registered to MRI (SISCOM) assist in focus localization and surgical planning for patients with medically intractable focal epilepsy. While the localizing value of SISCOM has been widely investigated, its relationship to the underlying electrophysiology has not been extensively studied and is therefore not well understood. In the present study, we set to investigate this relationship in a cohort of 70 consecutive patients who underwent ictal and interictal SPECT studies and subsequent stereo-electroencephalography (SEEG) monitoring for localization of the epileptogenic focus and surgical intervention. Seizures recorded during SEEG evaluation (SEEG seizures) were matched to semiologically-similar seizures during the preoperative ictal SPECT evaluation (SPECT seizures) by comparing the semiological changes in the course of each seizure. The spectral changes of the ictal SEEG with respect to interictal ones over 7 traditional frequency bands (0.1 to 150Hz) were analyzed at each SEEG site. Neurovascular (SEEG/SPECT) relations were assessed by comparing the estimated spectral power density changes of the SEEG at each site with the perfusion changes (SISCOM z-scores) estimated from the acquired SISCOM map at that site. Across patients, a significant correlation (p

Background Assistive automatic seizure detection can empower human annotators to shorten patient monitoring data review times. We present a proof-of-concept for a seizure detection system that is sensitive, automated, patient-specific, and tunable to maximise sensitivity while minimizing human annotation times. The system uses custom data preparation methods, deep learning analytics and electroencephalography (EEG) data. Methods Scalp EEG data of 365 patients containing 171,745 s ictal and 2,185,864 s interictal samples obtained from clinical monitoring systems were analysed as part of a crowdsourced artificial intelligence (AI) challenge. Participants were tasked to develop an ictal/interictal classifier with high sensitivity and low false alarm rates. We built a challenge platform that prevented participants from downloading or directly accessing the data while allowing crowdsourced model development. Findings The automatic detection system achieved tunable sensitivities between 75.00% and 91.60% allowing a reduction in the amount of raw EEG data to be reviewed by a human annotator by factors between 142x, and 22x respectively. The algorithm enables instantaneous reviewer-managed optimization of the balance between sensitivity and the amount of raw EEG data to be reviewed. Interpretation This study demonstrates the utility of deep learning for patient-specific seizure detection in EEG data. Furthermore, deep learning in combination with a human reviewer can provide the basis for an assistive data labelling system lowering the time of manual review while maintaining human expert annotation performance. Funding IBM employed all IBM Research authors. Temple University employed all Temple University authors. The Icahn School of Medicine at Mount Sinai employed Eren Ahsen. The corresponding authors Stefan Harrer and Gustavo Stolovitzky declare that they had full access to all the data in the study and that they had final responsibility for the decision to submit for publication.

Most seizures in adults with epilepsy occur rather infrequently and as a result, the interictal EEG plays a crucial role in the diagnosis and classification of epilepsy. However, empirical interpretation, of a first EEG in adult patients, has a very low sensitivity ranging between 29–55 %. Useful EEG information remains buried within the signals in seizure-free EEG epochs, far beyond the observational capabilities of any specialised physician in this field. Unlike most of the existing works focusing on either seizure data or single-variate method, we introduce a multi-variate method to characterise sensor level brain functional connectivity from interictal EEG data to identify patients with generalised epilepsy. A total of 9 connectivity features based on 5 different measures in time, frequency and time-frequency domains have been tested. The solution has been validated by the K-Nearest Neighbour algorithm, classifying an epilepsy group (EG) vs healthy controls (HC) and subsequently with another cohort of patients characterised by non-epileptic attacks (NEAD), a psychogenic type of disorder. A high classification accuracy (97 %) was achieved for EG vs HC while revealing significant spatio-temporal deficits in the frontocentral areas in the beta frequency band. For EG vs NEAD, the classification accuracy was only about 73 %, which might be a reflection of the well-described coexistence of NEAD with epileptic attacks. Our work demonstrates that seizure-free interictal EEG data can be used to accurately classify patients with generalised epilepsy from HC and that more systematic work is required in this direction aiming to produce a clinically useful diagnostic method.

Highlights • We applied Hidden Markov Model (HMM) to concurrent MEG and intracranial EEG (iEEG). • Epilepsy cohort HMM analysis yielded states similar to those of healthy subjects. • iEEG power correlated with the time course of HMM states. • Functional clusters of iEEG electrodes agreed with those based on spatial location. • Our pipeline can be used for group analysis of concurrent MEG and invasive data., Background Intracranial electroencephalography (iEEG) recordings are used for clinical evaluation prior to surgical resection of the focus of epileptic seizures and also provide a window into normal brain function. A major difficulty with interpreting iEEG results at the group level is inconsistent placement of electrodes between subjects making it difficult to select contacts that correspond to the same functional areas. Recent work using time delay embedded hidden Markov model (HMM) applied to magnetoencephalography (MEG) resting data revealed a distinct set of brain states with each state engaging a specific set of cortical regions. Here we use a rare group dataset with simultaneously acquired resting iEEG and MEG to test whether there is correspondence between HMM states and iEEG power changes that would allow classifying iEEG contacts into functional clusters. Methods Simultaneous MEG-iEEG recordings were performed at rest on 11 patients with epilepsy whose intracranial electrodes were implanted for pre-surgical evaluation. Pre-processed MEG sensor data was projected to source space. Time delay embedded HMM was then applied to MEG time series. At the same time, iEEG time series were analyzed with time-frequency decomposition to obtain spectral power changes with time. To relate MEG and iEEG results, correlations were computed between HMM probability time courses of state activation and iEEG power time course from the mid contact pair for each electrode in equally spaced frequency bins and presented as correlation spectra for the respective states and iEEG channels. Association of iEEG electrodes with HMM states based on significant correlations was compared to that based on the distance to peaks in subject-specific state topographies. Results Five HMM states were inferred from MEG. Two of them corresponded to the left and the right temporal activations and had a spectral signature primarily in the theta/alpha frequency band. All the electrodes had significant correlations with at least one of the states (p

Epilepsy is one of the most widespread neurological disorders worldwide that in some cases could be life threatening. We introduce a two-stage wavelet-based classification framework for preictal state detection. This framework utilizes a novel detail coefficients zero-crossings feature extracted from electroencephalography (EEG) activity. In the first stage, a machine learning algorithm classifies EEG data into interictal or preictal classes. In the second stage, another classifier further classifies preictal data to early or late preictal. We applied this framework to 22-channel EEG data recorded from 8 patients. The first stage of the framework achieves a mean accuracy of 94% using only 10 min of training data. The second stage discriminates between early and late preictal states with a mean accuracy of 80.5%. These results indicate the efficacy of the introduced framework in predicting seizures onset which could have a significant impact on the quality of life of epileptic patients.

Previously seizures have been reported as presenting neurological manifestation with COVID-19 infection. There is a growing literature on the delayed neurologic effects of COVID-19 infection. Here, we report a case with insidious onset of focal impaired awareness seizures associated with left temporal epileptiform interictal and ictal discharges consistent with focal epilepsy; occurring within a short time frame of the diagnosis of COVID-19 infection. This may be possibly a post COVID-19 inflammatory syndrome manifesting as new onset focal epilepsy with focal non-motor seizures with impaired awareness. As implicated by presentation with seizure as in our case, longterm follow-up studies are warranted to further investigate if the patients who acquire COVID-19 infection are at increased risk of developing epilepsy as a delayed manifestation.

PURPOSE There are multidien patterns of seizure occurrence. Predicting seizure risk may be easier with biomarker correlates to multidien patterns. We hypothesize multiday hyper or hypoglycemia contributes to seizure risk. METHODS In a type I diabetic (T1D) with focal onset epilepsy with continuous glucose monitoring (CGM) and responsive neurostimulation (RNS) devices, we studied multiday interictal activities (IEA), seizures, and glucose. Hourly CGM data was matched to hourly RNS captures of interictal and ictal activities over 33 months. RNS detection settings were unchanged. Multidien cycles were analyzed, active blocks of IEA and ictal episodes defined, and tissue glucose averages studied. RESULTS Average glucose was 161���mg/dl. A 40-day cycle of interictal and ictal activities occurred, though no similar glucose cycle was evident. Glucose elevations relative to patient average were associated with increases in IEA but not seizure. Frequent seizures were not associated with obvious elevations or decreases of glucose from baseline, most seizures occurred at +/- 10���mg/dl of average daily glucose (i.e. 150-170���mg/dl). CONCLUSION Tissue glucose may influence IEA but may not influence multiday seizure activity or very frequent seizures. In an ambulatory T1D patient multiday hypo or hyperglycemic extremes do not appear to provoke seizure activities.

The electroencephalogram (EEG) is the most important method to diagnose epilepsy. In clinical settings, it is evaluated by experts who identify patterns visually. Quantitative EEG is the application of digital signal processing to clinical recordings in order to automatize diagnostic procedures, and to make patterns visible that are hidden to the human eye. The EEG is related to chemical biomarkers, as electrical activity is based on chemical signals. The most well-known chemical biomarkers are blood laboratory tests to identify seizures after they have happened. However, research on chemical biomarkers is much less extensive than research on quantitative EEG, and combined studies are rarely published, but highly warranted. Quantitative EEG is as old as the EEG itself, but still, the methods are not yet standard in clinical practice. The most evident application is an automation of manual work, but also a quantitative description and localization of interictal epileptiform events as well as seizures can reveal important hints for diagnosis and contribute to presurgical evaluation. In addition, the assessment of network characteristics and entropy measures were found to reveal important insights into epileptic brain activity. Application scenarios of quantitative EEG in epilepsy include seizure prediction, pharmaco-EEG, treatment monitoring, evaluation of cognition, and neurofeedback. The main challenges to quantitative EEG are poor reliability and poor generalizability of measures, as well as the need for individualization of procedures. A main hindrance for quantitative EEG to enter clinical routine is also that training is not yet part of standard curricula for clinical neurophysiologists.

Highlights • Migraine patients were scanned by a 1H-MRS protocol optimized to target the pons. • Measurements were repeated on two separate days to increase accuracy. • Pontine glutamate levels were not increased outside attacks in patients. • Interestingly, interictal pontine total creatine levels were increased in patients. • Imbalanced pontine energy metabolism may be a potential imaging marker in migraine., In the pons, glutamatergic mechanisms are involved in regulating inhibitory descending pain modulation, serotoninergic neurotransmission as well as modulating the sensory transmission of the trigeminovascular system. Migraine involves altered pontine activation and structural changes, while biochemical, genetic and clinical evidence suggests that altered interictal pontine glutamate levels may be an important pathophysiological feature of migraine abetting to attack initiation. Migraine without aura patients were scanned outside attacks using a proton magnetic resonance spectroscopy protocol optimized for the pons at 3 Tesla. The measurements were performed on two separate days to increase accuracy and compared to similar repeated measurements in healthy controls. We found that interictal glutamate (i.e. Glx) levels in the pons of migraine patients (n = 33) were not different from healthy controls (n = 16) (p = 0.098), while total creatine levels were markedly increased in patients (9%, p = 0.009). There was no correlation of glutamate or total creatine levels to migraine frequency, days since the last attack, usual pain intensity of attacks or disease duration. In conclusion, migraine is not associated with altered interictal pontine glutamate levels. However, the novel finding of increased total creatine levels suggests that disequilibrium in the pontine energy metabolism could be an important feature of migraine pathophysiology.

Epilepsy is a disorder characterized by recurrent seizures. Epilepsy can alter mood and emotions. Treatments for epilepsy can also alter mood and emotions. This chapter reviews the emotional changes that can occur before, during, and after a seizure, such as fear and anger, the interictal mood disorders associated with epilepsy, such as depression and anxiety, as well as alterations of emotional processing including comprehending and expressing emotional prosody and faces. The possible treatments of these emotional and mood disorders are also reviewed.

Summary Automated seizure detection in long-term video-EEG recordings is far from being integrated into common clinical practice. Here, we leverage classical and state-of-the-art complexity measures to robustly and automatically detect seizures from scalp recordings. Brain activity is scored through eight features, encompassing traditional time domain and novel measures of recurrence. A binary classification algorithm tailored to treat unbalanced dataset is used to determine whether a time window is ictal or non-ictal from its features. The application of the algorithm on a cohort of ten adult patients with focal refractory epilepsy indicates sensitivity, specificity, and accuracy of 90%, along with a true alarm rate of 95% and less than four false alarms per day. The proposed approach emphasizes ictal patterns against noisy background without the need of data preprocessing. Finally, we benchmark our approach against previous studies on two publicly available datasets, demonstrating the good performance of our algorithm., Graphical Abstract, Highlights • Complexity measures are formulated to enhance classical time-domain statistics of EEG • The detection algorithm does not need ad-hoc data preprocessing to address artifacts • Focal seizures are detected 95% of the time with less than four false alarms per day • The approach offers a visual representation of a seizure as a time-evolving network, Computer Application in Medicine; Computer-Aided Diagnosis Method; Clinical Neuroscience; Techniques in Neuroscience; Algorithms

Ictal arrhythmias are disturbances of cardiac conduction that occur during clinical or electrographic seizures. Ictal asystole (IA) is rare, and its incidence can range from 0.3–0.4% in patients with epilepsy who were monitored by video-EEG (van der Lende et al., 2015). We report on ten patients (six males and four females) with an age ranging from 31 to 70 years old) who were monitored in our video-EEG (VEEG) unit over the last eight years. These patients were selected based on the history of documented ictal asystole during inpatient VEEG monitoring). In our series the mean latency from the seizure onset to the onset of ictal asystole was 22 seconds and the mean duration of the IA was 15.8 seconds. During the asystolic phase the seizures may clinically continue or syncopal signs may supervene. In our case series all the patients had either left or right temporal lobe epilepsy, six of which were lesional. We found two patterns of ictal semiology in our series. The first group of patients included five patients who experienced a rapid onset of IA in their seizure and the second group where the latency of ictal asystole was relatively late. All our cohort had a permanent pacemaker following the diagnosis, six of these patients have been event free since placement.

The occurrence of epileptic seizures is a problem that makes everyday life difficult for many people who suffer from this disorder, which may causes risks to the subjects and people around them. The possibility of predicting epileptic seizures could create a way to minimize risks associated with these attacks. Through computational analysis of Electroencephalography (EEG) signals, a variation of Recurrent Artificial Neural Network (RNN), of Long Short Term Memory (LSTM) type, was developed in an attempt to classify segments of EEG signals that occur before the onset of epileptic seizures, segments which evince the pre-ictal state. Using an EEG database of pediatric subjects with intractable seizures, groups of patients were created, then redundant EEG channels were selected and reduced by only 25%. Temporal and spectral features were extracted to improve the evaluation of data patterns related to seizures. Besides using the unprocessed data, two techniques were proposed, first using the superposition of inputs, then anticipating targets in the training data. A third technique was also proposed by joining the first two. Finally, two LSTM structures were created. The proposed Neural Network achieved high accuracies above 99%; however, the results showed that it was not possible to classify pre-ictal regions by using this combination of architecture and individuals. Furthermore, it was observed that the Neural Network was able to classify ictal regions with up to 61% sensitivity and 99% specificity, confirming the capacity of RNNs of LSTM type to assimilate temporal patterns in EEG data.

Background Hippocampal and cortical slice-based models are widely used to study seizures and epilepsy. Seizure detection and quantification are essential components for studying mechanisms of epilepsy and assessing therapeutic interventions. To obtain meaningful signals and maximize experimental throughput, variability should be minimized. Some electrical recording methods require insertion of an electrode into neuronal tissue, change in slice chemical microenvironment, and transients in temperature and pH. These perturbations can cause acute and long-term alterations of the neuronal network which may be reflected in the variability of the recorded signal. New method In this study we investigated the effect of experimental perturbations in three local field potential (LFP) recording methods including substrate micro-wires (s-MWs), multiple electrode arrays (MEAs), and inserted micro wire electrodes (i-MW). These methods enabled us to isolate effects of different perturbations. We used organotypic hippocampal slices (OHCs) as an in-vitro model of posttraumatic epilepsy. To investigate the effect of the disturbances caused by the recording method on the paroxysmal events, we introduced jitter analysis, which is sensitive to small differences in the seizure spike timing. Results Medium replacement can introduce long-lasting perturbations. Electrode insertion increased variability on a shorter time scale. OHCs also underwent spontaneous state transitions characterized by transient increases in variability. Comparison with existing methods This new method of seizure waveform analysis allows for more sensitive assessment of variability of ictal events than simply measuring seizure frequency and duration. Conclusion We demonstrated that some of the variability in OHC recordings are due to experimental perturbations while some are spontaneous and independent of recording method.

Ictal visual hallucinations may have occipital as well as temporal lobe origin. We report a patient with clustering of focal aware seizures with visual hallucinations. Ictal EEG findings and seizure semiology with alternating contralateral elementary visual phenomena and non-lateralizing experiential hallucinations (visual scenes, memory flashbacks, spatial distortion) corresponded to a lesion in the posterior part of the right parahippocampal gyrus. This area is part of the hippocampal-parahippocampal system for mapping allocentric space. Within this system, the parahippocampal cortex encodes information about visual environmental scenes in concert with functionally defined neurons relevant for episodic memory and spatial cognitive processes (place, grid, border and head direction cells, as well as neurons tracking the passage of time). These functions are tightly linked to visual exploration. We suggest that the hippocampal-parahippocampal spatial navigation system is a crucial part of the networks responsible for the semiology of experiential seizures with complex visual hallucinations and elements of recall., Highlights • Ictal visual hallucinations may have occipital or temporal lobe origin. • In temporal lobe epilepsy, they may be experiential and non-lateralized. • In the present patient, such seizures were related to a parahippocampal lesion. • This area overlaps with the spatial representation systems of the brain. • A more precise outline of the substrate for experiential seizures is suggested.

Up to 11% of patients with mesial temporal lobe epilepsy experience somatosensory auras, although these structures do not have any somatosensory physiological representation. We present the case of a patient with left mesial temporal lobe epilepsy who had somatosensory auras on the right side of the body. Stereo-EEG recording demonstrated seizure onset in the left mesial temporal structures, with propagation to the sensory cortices, when the patient experienced the somatosensory aura. Direct electrical stimulation of both the left amygdala and the hippocampus elicited the patient's habitual, somatosensory aura, with afterdischarges propagating to sensory cortices. These unusual responses to cortical stimulation suggest that in patients with epilepsy, aberrant neural networks are established, which have an essential role in ictogenesis., Highlights • Patients with mesial temporal lobe epilepsy may experience somatosensory auras. • Seizure activity propagated from mesial temporal structures to the sensory cortices. • Stimulation in the amygdala and hippocampus elicited habitual somatosensory aura. • We recorded afterdischarges propagating to insula and posterior cingulate contacts.

Background Intrauterine infection with the Zika virus (ZIKV) has been connected to severe brain malformations, microcephaly, and abnormal electrophysiological activity. Methods We describe the interictal electroencephalographic (EEG) recordings of 47 children born with ZIKV-derived microcephaly. EEGs were recorded in the first year of life and correlated with brain morphology. In 31 subjects, we tested the association between computed tomography (CT) findings and interictal epileptiform discharges (IED). In eighteen, CTs were used for correlating volumetric measurements of the brainstem, cerebellum, and prosencephalon with the rate of IED. Findings Twenty-nine out of 47 (62%) subjects were diagnosed as having epilepsy. Those subjects presented epileptiform discharges, including unilateral interictal spikes (26/29, 90%), bilateral synchronous and asynchronous interictal spikes (21/29, 72%), and hypsarrhythmia (12/29, 41%). Interestingly, 58% of subjects with clinical epilepsy were born with rhombencephalon malformations, while none of the subjects without epilepsy showed macroscopic abnormalities in this region. The presence of rhombencephalon malformation was associated with epilepsy (odds ratio of 34; 95% CI: 2 - 654). Also, the presence of IED was associated with smaller brain volumes. Age-corrected total brain volume was inversely correlated with the rate of IED during sleep. Finally, 11 of 44 (25%) subjects presented sleep spindles. We observed an odds ratio of 0·25 (95% CI: 0·06 - 1·04) for having sleep spindles given the IED presence. Interpretation The findings suggest that certain CT imaging features are associated with an increased likelihood of developing epilepsy, including higher rates of IED and impaired development of sleep spindles, in the first year of life of CZVS subjects. Funding This work was supported by the Brazilian Federal Government through a postdoctoral fellowship for EBS (Talented Youth, Science without Borders), an undergraduate scholarship for AJR (Institutional Program of Science Initiation Scholarships, Federal University of Rio Grande do Norte, Brazil), by International Centre for Genetic Engineering and Biotechnology (CRP/BRA18–05_EC) and by CAPES (Grant number 440893/2016-0), and CNPq (Grant number 88881.130729/2016-01).

Polyspike ictal-onset absence seizure has been reported in adult patients with genetic generalized epilepsy but is a novel pattern in the pediatric population. Absence seizures are usually associated with generalized spike-and-wave on EEG. However, we present the case of a 10-year-old girl with Down syndrome and developmental delays who presented with atypical absence seizure associated with an unusual electroencephalographic (EEG) pattern of polyspike ictal-onset. Recognition of this ictal pattern in the pediatric population, as previously reported in adult populations, is important as it can have therapeutic and prognostic implications., Highlights • Absence seizures are usually associated with generalized spike and wave, but here we report a polyspike ictal-onset pattern. • The pattern appeared as purely a polyspike ictal-onset, or polyspikes intermixed or preceding the generalized spike and wave. • Polyspike ictal onset is differentiated from generalized paroxysmal fast activity (GPFA), by morphology & other features.

We report the case of an adult psychiatric patient who developed new-onset focal bilateral motor seizures (FBMS) in the context of a severe benzodiazepine withdrawal syndrome. The patient was forced to interrupt chronic lormetazepam abuse and overdosed on amitriptyline (800 mg in an oral solution) before the onset of seizures. Typical signs of amitriptyline intoxication such as sedation and anticholinergic effects were not observed. Video-EEG recordings revealed a stereotypical ictal motor pattern with asymmetric tonic posturing and bilateral clonic movements of the upper limbs, but there were no abnormalities identified by EEG. Seizures recurred multiple times per day but resolved simultaneously when withdrawal symptomatology subsided eight days after onset. Nonepileptic seizures (NES) were considered in the differential diagnosis because of the patient's psychiatric history including preserved awareness during the bilateral convulsions, the absence of postictal confusion, and normal EEG. The present case indicates that FBMS may occur during benzodiazepine withdrawal in patients who overdosed on amitriptyline. The diagnosis may be challenging as FBMS may mimic NES in the absence of abnormal neurophysiologic findings. This may be especially challenging in patients with an underlying psychiatric disease., Highlights • Focal onset seizures may be observed in patients with benzodiazepine withdrawal syndrome. • Focal bilateral motor seizures may mimic nonepileptic seizures in psychiatric patients with normal EEG findings. • The use of lormetazepam in the form of an oral solution containing ethanol should be carefully monitored to prevent abuse.

We report a novel case of an infant with neurofibromatosis type 1 (NF1) who presented with new onset presumed focal impaired awareness seizures with motor onset followed by rapid progression to infantile spasms (IS). Electroencephalography (EEG) captured evolution from focal epileptiform discharges to multifocal and generalized discharges, then to hypsarrhythmia over three days. Development of IS within days of focal seizure onset is rapid, and to our knowledge, has not been demonstrated electrographically. The pattern of rapid ictal transition to hypsarrhythmia is essential for neurologists to be able to recognize as it can help lead to early treatment, which is necessary for improved outcomes in IS., Highlights • Patients with a non-lesional MRI in NF1 are at risk for epilepsy and infantile spasms. • The dynamic period between focal seizures and infantile spasms can be rapid. • The pattern of rapid ictal transition to hypsarrhythmia is important for early treatment.

Pathological high-frequency oscillations (HFOs), specifically fast ripples (FRs, >250 Hz), are pathognomonic of an active epileptogenic zone. However, the origin of FRs remains unknown. Here we explored the correlation between FRs recorded with intraoperative pre-resection electrocorticography (ECoG) and spontaneous synaptic activity recorded ex vivo from cortical tissue samples resected for the treatment of pharmacoresistant epilepsy. The cohort included 47 children (ages 0.22–9.99 yr) with focal cortical dysplasias (CD types I and II), tuberous sclerosis complex (TSC) and non-CD pathologies. Whole-cell patch clamp recordings were obtained from pyramidal neurons and interneurons in cortical regions that were positive or negative for pathological HFOs, defined as FR band oscillations (250–500 Hz) at ECoG. The frequency of spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and IPSCs, respectively) was compared between HFO+ and HFO- regions. Regardless of pathological substrate, regions positive for FRs displayed significantly increased frequencies of sIPSCs compared with regions negative for FRs. In contrast, the frequency of sEPSCs was similar in both regions. In about one third of cases (n = 17), pacemaker GABA synaptic activity (PGA) was observed. In the vast majority (n = 15), PGA occurred in HFO+ areas. Further, fast-spiking interneurons displayed signs of hyperexcitability exclusively in HFO+ areas. These results indicate that, in pediatric epilepsy patients, increased GABA synaptic activity is associated with interictal FRs in the epileptogenic zone and suggest an active role of GABAergic interneurons in the generation of pathological HFOs. Increased GABA synaptic activity could serve to dampen excessive excitability of cortical pyramidal neurons in the epileptogenic zone, but it could also promote neuronal network synchrony.

Aphasic status epilepticus (SE) is a clinical entity of SE, but it has not been well recognized. We report a 43-year-old female with a chronic drug-resistant epilepsy with aphasic SE, treated by resective surgery. The patient showed long-lasting weekly episodes of hypokinesia, slow verbal response, and dysphasia, which were diagnosed as symptoms of aphasic SE. Magnetic resonance imaging showed encephalomalacia in the left frontal lobe with a hemosiderin rim. Intracranial electroencephalography revealed continuous spikes, predominantly on the left superior frontal gyrus with hemosiderin deposit. The aphasic symptoms were seen when ictal discharges gradually spread to the wide area of the left anterior frontal lobe, including the language area. The episodes of recurrent aphasic SE had disappeared by one year after the left anterior frontal resection. We should consider aphasic SE when language impairment is episodic, and consider surgical intervention in cases where it repeatedly occurs despite appropriate medical therapy., Highlights • Long-lasting slow verbal response and dysphasia could be manifestations of aphasic status epilepticus of frontal origin • Epilepsy surgery should be considered for repeat aphasic SE under appropriate medical treatment after definite diagnosis • Precise time correlations between aphasic symptoms and ictal discharges could be unclear even by intracranial electroencephalography.

Highlights • Inpatient VEEG study is the gold standard in patients with TLE undergoing presurgical evaluation. • VEEG is expensive and not available for a significant proportion of patients in developing countries. • AmbEEG may be used instead of VEEG to identify candidates for temporal lobectomy in selected patients with refractory TLE and concordant semiology, unilateral EEG, neuroimaging and neuropsychological data., Purpose Inpatient Video EEG Monitoring (VEM) is the typical study performed in presurgical evaluations. It is expensive and not widely available in developing countries. Recent studies suggested that in selected patients with mesial temporal lobe epilepsy secondary to unilateral mesial temporal sclerosis (MTS), the recording of unilateral interictal epileptiform activity ipsilateral to the MTS may yield sufficient presurgical EEG data. Outpatient prolonged ambulatory EEG (AEEG) could be an alternative in these cases. The purpose of this study was to compare the post-surgical seizure outcome and costs between patients evaluated with AEEG versus VEM. Methods Thirty patients with TLE were included: 21 evaluated with VEM and 9 with AmbEEG and underwent surgery between 2011 and 2017. The minimum, post-surgical follow-up period was 1 year. Results Seven of nine patients who underwent AEEG had seizures ipsilateral to MTS. In two patients only unilateral interictal activity ipsilateral to the lesion was recorded. All patients were free of disabling seizures (Engel Class I) at last follow-up. The mean cost per patient of AEEG was $980 and was $4680 for VEM. Conclusion AEEG may be used to identify candidates for temporal lobectomy in selected patients with unilateral lesional mesial TLE. This approach to EEG monitoring could make epilpesy surgery more affordable to some patients in developing countries.

An epileptic seizure during the course of driving can result in a serious car accident. However, basic data on how epileptic seizures actually affect driving performance is significantly lacking. To understand the relationship, it is crucial to conduct not only behavioral but also electroencephalogram (EEG) analysis during epileptic seizures. Therefore, we developed a mobile driving simulator which makes it possible to record driving-related parameters time-lined with video-EEG. We report a case in which behavioral and EEG changes were successfully recorded during ictal periods of focal impaired awareness seizure in a patient engaged with the system. With the current lack of objective data describing how seizures impair driving performance, such an accumulation of information could improve personalized medical management, influence legal adjudication and assist in the development of driving support systems for people with epilepsy., Highlights • A driving simulator system with simultaneous video-EEG recording was constructed. • The system was assembled at a reasonably low cost. • A TLE patient had a focal impaired awareness seizure during a driving task. • Timeline data of seizure evolution and driving impairment was directly recorded. • Throttle control ability had already been lost before the EEG signal change.

Purpose To evaluate the yield of Functional Connectivity (FC) in addition to low-density ictal Electrical Source Imaging (ESI) in extratemporal lobe epilepsy (ETLE), using an automated algorithm for analysis. Method Long-term EEG monitoring of consecutive ETLE patients who underwent surgery was reviewed by epileptologists, and seizure onsets characterized by rhythmical activity were identified. A spectrogram-based algorithm was developed to select objectively the parameters of ESI analysis. Two methods for SOZ localization were compared: i) ESI power, based on LORETA exclusively; ii) ESI + FC, including a Granger causality-based connectivity analysis. Results were determined at a sublobar level. The resection zone, in relation to 1-year follow-up surgical outcome, was considered as reference standard for diagnostic accuracy analyses. Results Ninety-four seizures from 24 patients were analyzed. At seizure-level, ESI power showed 36 % sensitivity and 72 % specificity (accuracy: 45 %). ESI + FC significantly improved the accuracy, with 52 % sensitivity and 84 % specificity (accuracy: 61 %, p = 0.04). Results of ESI + FC were equally valuable in patients with lateralized or bilateral/generalized visual interpretation of ictal EEG. In a patient level sub-analysis, upon blinded clinical interpretation, ESI + FC showed a correct localization in 67 % of patients and substantial inter-rater agreement (kappa = 0.64), against 27 % achieved by ESI power, with fair inter-rater agreement (kappa = 0.37). Conclusion FC significantly improves SOZ localization compared to ESI solely in ETLE. Ictal ESI + FC could represent a novel option in the armamentarium of presurgical evaluation, aiding also in patients with visually non-localizable scalp ictal EEG. Prospective studies evaluating the clinical added value of automated low-density ictal ESI may be justified.

Highlights • The aim of this study is to investigate changes in metabolic networks in patients with drug-resistant TLE. • TLE patients with HS show alterations of metabolic connectivity compared to those without HS. • This may represent distinct epileptic networks in TLE patients with HS versus those without HS., Objective The aim of this study is to investigate changes in metabolic networks based on fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with drug-resistant temporal lobe epilepsy (TLE) (with and without hippocampal sclerosis [HS]) when compared with healthy controls. Methods We retrospectively enrolled 30 patients with drug-resistant temporal lobe epilepsy (17 patients with HS and 13 patients without HS) and 39 healthy controls. All subjects underwent interictal FDG-PET scans, which were analyzed to obtain metabolic connectivity using graph theoretical analysis. We investigated the differences in metabolic connectivity between patients with drug-resistant TLE (with and without HS) and healthy controls. Results When compared with healthy controls, TLE patients with HS showed alterations of global and local metabolic connectivity. When considering global connectivity, TLE patients with HS had a decreased average degree with increased modularity. When considering local connectivity, TLE patients with HS displayed alterations of betweeness centrality in widespread regions. However, there were no alterations of global metabolic connectivity in TLE patients without HS when compared with healthy controls. In addition, when compared to TLE patients without HS, TLE patients with HS had increased modularity. Significance Our study demonstrates more severe alterations in metabolic networks based on FDG-PET in TLE patients with HS than in those without HS and healthy controls. This may represent distinct epileptic networks in TLE patients with HS versus those without HS, although both are drug-resistant focal epilepsy.

“Burst-suppression” pattern consists of complete attenuation of background between bursts of mixed frequencies, variable morphology and waveforms. It is a subgroup of periodic patterns seen in severe cerebral damage, anesthesia or prematurity. Here, we present a 46-year-old woman with post-anoxic encephalopathy on cooling protocol with two electrographically similar patterns of burst-suppression (one with a clinical ictal correlate of isolated eye movements), as well as three electroclinical seizures. The literature on rare clinical phenomenon of isolated eye movements associated with burst-suppression is reviewed, with the conclusion that the presented case suggests an ictal origin., Highlights • Isolated eye movements associated with burst-suppression are rare clinical phenomena • Majority of authors consider these eye movements to be of brain stem origin. • A case of isolated eye movements with burst-suppression is presented in which there is temporal and clinical correlation of abnormal eye movements to the bursts and to three electroclinical seizures • The presented case reflects the influence of excitatory cortical activity over the involved pathways and therefore is highly suggestive of an ictal nature

Ictal syncope is a rare phenomenon that occurs in association with 0.002–0.4% of seizures. In the absence of other symptoms, seizures presenting with syncope may be challenging to diagnose. We report a case of a previously healthy male who developed recurrent episodes of syncope with postictal confusion and was later diagnosed with temporal seizures. The patient was successfully treated with anti-seizure drugs and placement of a cardiac pacemaker. In a systematic review of literature, we summarize the clinical characteristics of patients with ictal asystole and isolated syncope. Seizures should be considered in patients with syncope of uncertain etiology., Highlights • Focal seizures leading to bradycardia-asystole can be accompanied by sudden atonia with loss of consciousness • Ictal syncope as the only symptom of seizure represents an exceptionally rare phenomena that may mimic other paroxysmal neurological events • Patients with recurrent syncopal events of uncertain etiology should have seizures considered in the differential diagnosis