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Interictal epileptiform discharges (IEDs) such as spikes and sharp waves represent pathological electrophysiological activities occurring in epilepsy patients between seizures. IEDs occur preferentially during non-rapid eye movement (NREM) sleep and are associated with impaired memory and cognition. Despite growing interest, most studies involving IED detections rely on visual annotations or employ simple amplitude threshold approaches. Alternatively, advanced computerized detection methods are not standardized or publicly available. To address this gap, we introduce a novel dataset comprising multichannel intracranial electroencephalography (iEEG) data recorded at two medical centers during overnight sleep with IED annotations performed by expert neurologists. Utilizing these annotations to train machine learning models via a gradient-boosting algorithm, we demonstrate automated IED detection with high precision (94.4%) and sensitivity (94.3%) that can generalize across individuals and surpass performance of a leading commercial software. The dataset featuring multi-channel annotations with sub-second resolution including hippocampus and medial temporal lobe (MTL) regions is made publicly available, together with the detection algorithm, to advance research on detection methodology, epilepsy, sleep, and cognition., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Video EEG monitoring (VEM) is an important tool for characterizing clinical events suspected as seizures. It is also used for pre-surgical workups in patients with drug-resistant epilepsy (DRE). In-hospital VEM high cost, long admission waiting periods and some other inconveniences led to an interest in home VEM (HVEM). However, because antiseizure medications cannot be reduced at home, HVEM may require longer monitoring. While the economic aspect is one of the main motivations for HVEM, the cost of HVEM lasting several weeks has not been assessed., Methods: We modeled the cost of HVEM for 8 weeks and compared it to the cost of 1-week in-hospital VEM. Additionally, we modeled the per-patient cost for a combination of HVEM and in-hospital VEM, considering that if in a proportion of patients HVEM fails to achieve its goal, they should undergo in-hospital VEM with drug reduction., Results: The average cost of HVEM up to 4-6 weeks of monitoring was lower than that for the 1-week in-hospital VEM. Combining the 3-week HVEM with 1-week in-hospital VEM (if needed) reduced the per-patient cost by 6.6-28.6% as compared to the situation when all the patients with DRE were referred to the in-hospital VEM., Conclusions: A prolonged intermittent HVEM can be cost-effective, especially if the minimal seizure frequency is about one seizure per week. The study findings support directing efforts into clinical trials and technology development., (© 2024. The Author(s).)

Our ability to recall memories of personal experiences is an essential part of daily life. These episodic memories often involve movement through space and thus require continuous encoding of one's position relative to the surrounding environment. The medial temporal lobe (MTL) is thought to be critically involved, based on studies in freely moving rodents and stationary humans. However, it remains unclear if and how the MTL represents both space and memory especially during physical navigation, given challenges associated with deep brain recordings in humans during movement. We recorded intracranial electroencephalographic (iEEG) activity while participants completed an ambulatory spatial memory task within an immersive virtual reality environment. MTL theta activity was modulated by successful memory retrieval or spatial positions within the environment, depending on dynamically changing behavioral goals. Altogether, these results demonstrate how human MTL oscillations can represent both memory and space in a temporally flexible manner during freely moving navigation., (© 2023. Springer Nature Limited.)

Memory consolidation during sleep is thought to depend on the coordinated interplay between cortical slow waves, thalamocortical sleep spindles and hippocampal ripples, but direct evidence is lacking. Here, we implemented real-time closed-loop deep brain stimulation in human prefrontal cortex during sleep and tested its effects on sleep electrophysiology and on overnight consolidation of declarative memory. Synchronizing the stimulation to the active phases of endogenous slow waves in the medial temporal lobe (MTL) enhanced sleep spindles, boosted locking of brain-wide neural spiking activity to MTL slow waves, and improved coupling between MTL ripples and thalamocortical oscillations. Furthermore, synchronized stimulation enhanced the accuracy of recognition memory. By contrast, identical stimulation without this precise time-locking was not associated with, and sometimes even degraded, these electrophysiological and behavioral effects. Notably, individual changes in memory accuracy were highly correlated with electrophysiological effects. Our results indicate that hippocampo-thalamocortical synchronization during sleep causally supports human memory consolidation., (© 2023. The Author(s).)

Objective: The aim of this study was to evaluate the utility and safety of "hybrid" stereo-electroencephalography (SEEG) in guiding epilepsy surgery and in providing information at single-neuron levels (i.e., single-unit recording) to further the understanding of the mechanisms of epilepsy and the neurocognitive processes unique to humans., Methods: The authors evaluated 218 consecutive patients undergoing SEEG procedures from 1993 through 2018 at a single academic medical center to assess the utility and safety of this technique in both guiding epilepsy surgery and providing single-unit recordings. The hybrid electrodes used in this study contained macrocontacts and microwires to simultaneously record intracranial EEG and single-unit activity (hybrid SEEG). The outcomes of SEEG-guided surgical interventions were examined, as well as the yield and scientific utility of single-unit recordings in 213 patients who participated in the research involving single-unit recordings., Results: All patients underwent SEEG implantation by a single surgeon and subsequent video-EEG monitoring (mean of 10.2 electrodes per patient and 12.0 monitored days). Epilepsy networks were localized in 191 (87.6%) patients. Two clinically significant procedural complications (one hemorrhage and one infection) were noted. Of 130 patients who underwent subsequent focal epilepsy surgery with a minimum 12-month follow-up, 102 (78.5%) underwent resective surgery and 28 (21.5%) underwent closed-loop responsive neurostimulation (RNS) with or without resection. Seizure freedom was achieved in 65 (63.7%) patients in the resective group. In the RNS group, 21 (75.0%) patients achieved 50% or greater seizure reduction. When the initial period of 1993 through 2013 before responsive neurostimulator implantation in 2014 was compared with the subsequent period of 2014 through 2018, the proportion of SEEG patients undergoing focal epilepsy surgery grew from 57.9% to 79.7% due to the advent of RNS, despite a decline in focal resective surgery from 55.3% to 35.6%. A total of 18,680 microwires were implanted in 213 patients, resulting in numerous significant scientific findings. Recent recordings from 35 patients showed a yield of 1813 neurons, with a mean yield of 51.8 neurons per patient., Conclusions: Hybrid SEEG enables safe and effective localization of epileptogenic zones to guide epilepsy surgery and provides unique scientific opportunities to investigate neurons from various brain regions in conscious patients. This technique will be increasingly utilized due to the advent of RNS and may prove a useful approach to probe neuronal networks in other brain disorders.

How responsive neurostimulation (RNS) decreases seizure frequency is unclear. Stimulation may alter epileptic networks during inter-ictal epochs. Definitions of the epileptic network vary but fast ripples (FRs) may be an important substrate. We, therefore, examined whether stimulation of FR-generating networks differed in RNS super responders and intermediate responders. In 10 patients, with subsequent RNS placement, we detected FRs from stereo-electroencephalography (SEEG) contacts during pre-surgical evaluation. The normalized coordinates of the SEEG contacts were compared with those of the eight RNS contacts, and RNS-stimulated SEEG contacts were defined as those within 1.5 cm 3 of the RNS contacts. We compared the post-RNS placement seizure outcome to (1) the ratio of stimulated SEEG contacts in the seizure-onset zone (SOZ stimulation ratio [SR]); (2) the ratio of FR events on stimulated contacts (FR SR); and (3) the global efficiency of the FR temporal correlational network on stimulated contacts (FR SGe). We found that the SOZ SR (p = .18) and FR SR (p = .06) did not differ in the RNS super responders and intermediate responders, but the FR SGe did (p = .02). In super responders, highly active desynchronous sites of the FR network were stimulated. RNS that better targets FR networks, as compared to the SOZ, may reduce epileptogenicity more., (© 2023 International League Against Epilepsy.)

Advances in technologies that can record and stimulate deep brain activity in humans have led to impactful discoveries within the field of neuroscience and contributed to the development of novel therapies for neurological and psychiatric disorders. Further progress, however, has been hindered by device limitations in that recording of single-neuron activity during freely moving behaviors in humans has not been possible. Additionally, implantable neurostimulation devices, currently approved for human use, have limited stimulation programmability and restricted full-duplex bidirectional capability. In this study, we developed a wearable bidirectional closed-loop neuromodulation system (Neuro-stack) and used it to record single-neuron and local field potential activity during stationary and ambulatory behavior in humans. Together with a highly flexible and customizable stimulation capability, the Neuro-stack provides an opportunity to investigate the neurophysiological basis of disease, develop improved responsive neuromodulation therapies, explore brain function during naturalistic behaviors in humans and, consequently, bridge decades of neuroscientific findings across species., (© 2023. The Author(s).)

Responsive neurostimulation (RNS) is an effective treatment modality for refractory temporal lobe epilepsy (TLE). However, the optimal placement of RNS leads is not known. We use an orthogonal approach to lead placement instead of the more common longitudinal approach to target the entorhinal cortex (EC), given its potential for modulating activity entering and leaving the hippocampus. An orthogonal approach allows for coverage of the EC as well as the anterior lateral temporal cortex, which may be particularly beneficial for patients with mesial-lateral TLE and may also enable greater modulation of the limbic network. The objective of this study was to determine treatment outcomes for orthogonally placed RNS depth leads targeting the EC. We performed a retrospective analysis of prospectively collected data on a cohort of 13 patients. Mean follow-up duration was 57.3 months, and the 50% responder rate was 76.9%. These results show that orthogonally placed RNS leads are safe and effective for the treatment of refractory TLE. Larger cohorts are needed to further delineate the clinical utility of this novel targeting strategy., (© 2022 International League Against Epilepsy.)

Ambulatory "at home" video-EEG monitoring (HVEM) may offer a more cost-effective and accessible option as compared to traditional inpatient admissions to epilepsy monitoring units. However, home monitoring may not allow for safe tapering of anti-seizure medications (ASM). As a result, longer periods of monitoring may be necessary to capture a sufficient number of the patients' stereotypic seizures. We aimed to quantitatively estimate the necessary length of HVEM corresponding to various diagnostic scenarios in clinical practice. Using available seizure frequency statistics, we estimated the HVEM duration required to capture one, three, or five seizures on different days, by simulating 100,000 annual time-courses of seizure occurrence in adults and children with more than one and <30 seizures per month (89% of adults and 85% of children). We found that the durations of HVEM needed to record 1, 3, or 5 seizures in 80% of children were 2, 5, and 8 weeks (median 2, 12, and 21 days), respectively, and significantly longer in adults -2, 6, and 10 weeks (median 3, 14, and 26 days; p < 10 -10 for all comparisons). Thus, longer HVEM than currently used is needed for expanding its clinical value from diagnosis of nonepileptic or very frequent epileptic events to a presurgical tool for patients with drug-resistant epilepsy. Technical developments and further studies are warranted., Competing Interests: Authors MM and DEk are the inventors of patents related to HVEM development. Authors DEl, MM, and DEk are involved with VIRDA startup company, which develops HVEM systems. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vander, Stroganova, Doufish, Eliashiv, Gilboa, Medvedovsky and Ekstein.)

The relationship between antiseizure drugs and movement disorders is complex and not adequately reviewed so far. Antiseizure drugs as a treatment for tremor and other entities such as myoclonus and restless leg syndrome is the most common scenario, although the scientific evidence supporting their use is variable. However, antiseizure drugs also represent a potential cause of iatrogenic movement disorders, with parkinsonism and tremor the most common disorders. Many other antiseizure drug-induced movement disorders are possible and not always correctly identified. This review was conducted by searching for all the possible combinations between 15 movement disorders (excluding ataxia) and 24 antiseizure drugs. The main objective was to describe the movement disorders treated and worsened or induced by antiseizure drugs. We also summarized the proposed mechanisms and risk factors involved in the complex interaction between antiseizure drugs and movement disorders. Antiseizure drugs mainly used to treat movement disorders are clonazepam, gabapentin, lacosamide, levetiracetam, oxcarbazepine, perampanel, phenobarbital, pregabalin, primidone, topiramate, and zonisamide. Antiseizure drugs that worsen or induce movement disorders are cenobamate, ethosuximide, felbamate, lamotrigine, phenytoin, tiagabine, and vigabatrin. Antiseizure drugs with a variable effect on movement disorders are carbamazepine and valproate while no effect on movement disorders has been reported for brivaracetam, eslicarbazepine, lacosamide, and stiripentol. Although little information is available on the adverse effects or benefits on movement disorders of newer antiseizure drugs (such as brivaracetam, cenobamate, eslicarbazepine, lacosamide, and rufinamide), the evidence collected in this review should guide the choice of antiseizure drugs in patients with concomitant epilepsy and movement disorders. Finally, these notions can lead to a better understanding of the mechanisms involved in the pathophysiology and treatments of movement disorders., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Nodding syndrome (NS) is a poorly understood form of childhood-onset epilepsy that is characterized by the pathognomonic ictal phenomenon of repetitive vertical head drops. To evaluate the underlying ictal neurophysiology, ictal EEG features were evaluated in nine participants with confirmed NS from South Sudan, Tanzania, and Uganda and ictal presence of high frequency gamma oscillations on scalp EEG were assessed. Ictal EEG during the head nodding episode predominantly showed generalized slow waves or sharp-and-slow wave complexes followed by electrodecrement. Augmentation of gamma activity (30-70 Hz) was seen during the head nodding episode in all the participants. We confirm that head nodding episodes in persons with NS from the three geographically distinct regions in sub-Saharan Africa share the common features of slow waves with electrodecrement and superimposed gamma activity. ANN NEUROL 2022;92:75-80., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Acute kidney injury (AKI) is a frequent complication in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Identification of different AKI recovery patterns may improve patient prognostic stratification. We investigated the clinical relevance of AKI recovery patterns among STEMI patients undergoing PCI. Methods: A retrospective study of 2943 STEMI patients undergoing PCI. The incidence of renal impairment, in-hospital complications, short and long-term mortality, were compared between patients without AKI, with early recovery defined as a return to baseline creatinine within 72 h, and no AKI recovery/delayed recovery defined as all other AKI cases. Results: A total of 255 (8.7%) patients developed AKI, of whom 124/255 (49%) patients had an early recovery, whereas 131/255 (51%) had no AKI recovery/delayed recovery. Patients without recovery were more likely to have in-hospital complications and higher long-term mortality (36.64% vs. 7.25%%; p < 0.001). In a multivariable regression model, the mortality hazard ratio (HR) for long term mortality remained significant for patients with no/delayed recovery AKI (HR 7.76, 95% CI 4.69 to 12.86, p < 0.001), and a strong trend among patients with resolving AKI (HR 2.09, 95% CI 0.933−4.687, p = 0.071). Conclusions: Among STEMI patients undergoing PCI, the recovery pattern of AKI is a valuable prognostic marker.